2023 BME Innovations Magazine

FALL 2023

BME INNOVATIONS HISTOTRIPSY: Tumor-destroying soundwaves that received FDA approval for liver treatment in humans

FALL EDITION

Technique developed at the University of Michigan provides a non-invasive alternative to surgery, chemotherapy and radiation treatments for cancer.

Page No. 10

BUBBLES THAT KILL CANCER

Pioneered at the University of Michigan, histotripsy offers a promising alternative to common cancer treatments.

Page No. 20

MEET OUR 12 NEW FACULTY

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A message from the William and Valerie Hall Department Chair of Biomedical Engineering

LETTER FROM THE CHAIR

I am delighted to introduce you to our U-M BME Fall 2023 magazine, BME Innovations.

We selected this title because it captures the essence of our department and our direction for the future – the drive to constantly improve upon our past and imagine infinite possibilities moving forward.

This is an exciting time to be a part of the University of Michigan and our Biomedical Engineering community. Our publication reflects this sense of optimism and opportunity. As we introduce our 12 new core faculty members, highlight our research, showcase our award-winning faculty, staff and students, and profile our connections with our alumni and industry partners, we capture the energy that propels our department and inspires these innovations.

As the new William and Valerie Hall Department Chair of Biomedical Engineering, I am privileged to lead this group of creative, talented people who are developing innovative solutions to the greatest challenges confronting the engineering and medical professions. Together, we are working to advance our mission of leadership in education, research, and clinical translation to the benefit of humanity.

Articles in this issue go behind-the-scenes on our research and education, highlighting the breadth and depth of activity in BME. Other features showcase the talents of our faculty, staff, students, and alumni who have received university and professional recognition for their work in the community, clinic, laboratory and classroom.

U-M BME is uniquely positioned as a joint department between Michigan Engineering and the U-M Medical School. In addition, we offer collaborative research and educational opportunities with the many globally recognized schools of the University of Michigan, which is ranked as one of the top public universities in the United States.

As we plan for the future, we benefit from reflecting on the past. This magazine spotlights many of our recent accomplishments and celebrates our victories. As you read the articles, please visit our website, which will have a new look moving into 2024. We’re excited to share our news with you through our print and digital communications, and we hope you will continue to visit us either in person or virtually so we can share our latest innovations with you.

Thank you, and Go Blue!

Mary-Ann Mycek, Ph.D. William and Valerie Hall Department Chair, Biomedical Engineering Professor, Biomedical Engineering

BME innovations

CONTENTS 14 10 5 CHAIR ANNOUNCEMENT

28 REPRODUCTIVE HEALTH

HISTOTRIPSY

44 FACULTY HONORS

SURGEON-BME COLLABORATION

45 STUDENT HONORS

20 12 NEW FACULTY

58 IN MEMORIAM

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BME BY THE NUMBERS 2022-2023 Uniquely positioned as a joint department in both the College of Engineering and the Medical School, U-M’s Biomedical Engineering (BME) department is a leader in education, research, and clinical translation.

U-M BME has one of the oldest and largest biomedical engineering programs in the country.

700+

940+

STUDENTS

48

BME COMMUNITY MEMBERS

30

OPERATIONS STAFF

47

CORE FACULTY

POSTDOCS & RESEARCH STAFF

(PLUS >120 AFFILIATE & ASSOCIATE)

The BME student population has achieved gender equity with continual growth in underrepresented minorities.

BME is the

BME programs rank*:

#10

most popular undergraduate major on the U-M Ann Arbor Campus

#6

UNDERGRADUATE BME PROGRAM

#9

GRADUATE BME PROGRAM (MS/MSE/MENG/PHD)

*In the nation

U-M Office of Budget and Planning, Fall 2022

U.S. News & World Report, Best Colleges

BME Research Focus Areas: • Biomechanics • Computation & Modeling • Imaging & Biophotonics • Micro- & Nano- Technology & Molecular Engineering • Tissue Engineering & Regenerative Medicine

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STARTUPS LAUNCHED

$27M ANNUAL RESEARCH EXPENDITURES

39

PATENTS ISSUED

28

LICENSES

Professor Mycek officially appointed as BME chair

Professor Mary-Ann Mycek has been appointed the William and Valerie Hall Department Chair of Biomedical Engineering (BME), effective September 1, 2023, through August 30, 2028. U-M Regents voted on September 21, 2023, to confirm her appointment.

Professor Mycek has served as interim chair of BME since July 1, 2021. As interim chair, she was responsible for the education and welfare of more than 650 BME undergraduate and graduate students, while 13 new faculty members joined the department. She also served as the principal investigator for the Coulter Translational Research Partnership Program in BME – a $20M endowed program with a goal of creating a powerhouse of innovation in BME. The BME Coulter Program supports research directed at promising technologies within research laboratories that are progressing towards commercial development and clinical practice. As interim chair, Professor Mycek supported the development and implementation of several academic initiatives, including launching the first Master’s of Engineering degree program in BME, initiating the ongoing BME Exchange networking program for students, alumni and industry partners, and developing and launching BME Summer Workshops @ Michigan – an annual series on focused translational research topics for global participants hosted on-site

by BME faculty, staff and students.

“I enjoyed working with Professor Mycek when she was associate dean and appreciate the unique perspective she brings to this role,” said Steve Ceccio, interim dean of Michigan Engineering.

“I look forward to her continued leadership and collaboration as the William and Valerie Hall Department Chair of Biomedical Engineering.”

“We greatly appreciate Dr. Mycek’s strong leadership as interim

BME innovations chair since 2021, and we are thankful that she will now serve as chair of BME,” said Marschall S. Runge, MD, PhD, dean of the U-M Medical School. “During her tenure, BME has made tremendous strides in education and research, and we have every confidence that Dr. Mycek will lead the department to even greater heights during the next five years.”

“I’m truly honored to be appointed the William and Valerie Hall Department Chair of Biomedical Engineering at the University of Michigan,” said Professor Mycek. “I’m immensely proud of our U-M community of nearly 1,000 BME students, postdocs, research scientists, staff, and faculty, and the important work they do every day to realize our research and educational mission. Moving forward, I’m excited to work with the broader BME community and our friends to further promote and enable BME’s mission, and to expand the department’s impact for the benefit of humanity.”

Professor Mycek received her PhD in physics from the University of California at Berkeley, where she specialized in condensed matter physics and ultrafast optical spectroscopy, before pursuing postdoctoral training in laser medicine at Massachusetts General Hospital and Harvard Medical School. She was appointed as an assistant professor at Dartmouth College in 1998. Professor Mycek joined the faculty at U-M as an associate professor in 2003 and was awarded tenure in 2006. She has served as an associate chair of the BME Department twice: first as director of the BME Master’s and doctoral graduate programs and later as the associate chair for translational research. She was promoted to professor in 2012 and was appointed the associate dean for graduate education in Michigan Engineering in 2016. In 2018, her responsibilities were expanded to include online and professional engineering education and she was appointed the associate dean for graduate & professional education. In 2021, she was appointed the interim chair of the department of Biomedical Engineering, a joint department in the Michigan Engineering and the Medical School.

As associate dean for graduate and professional education, Professor Mycek served as the chief academic officer for graduate education in Michigan Engineering and was responsible for the education and welfare of more than 3,600 Master’s and PhD students engaged in over 60 graduate engineering degree programs. She was also responsible for the education and welfare of more than 1,900 Michigan Engineering online students and lifelong professional education learners. As associate dean, she co-led the Education pillar of our ME 2020 strategic vision, creating and implementing strategic initiatives and assessment plans related to CoE graduate, online, and professional education.

In 2018, she established the NextProf Nexus partnership with UC Berkeley and Georgia Tech. The partnership expanded access to Michigan Engineering’s NextProf Future Faculty Workshop, which is designed to encourage graduate students and postdoctoral fellows in traditionally underrepresented demographic groups to pursue academic careers. She also developed and implemented a centralized reporting framework and strategic communications plan for the Michigan Engineering Consultation, Assistance, and Resources in Engineering (C.A.R.E.) Center—the central hub for engineering student wellness—to identify and remedy student concerns. In 2019, she launched Nexus, Michigan Engineering’s home for online and professional engineering education.

Established just prior to the pandemic, Nexus provided both strategic and operational advantages during the remote-learning transition.

Professor Mycek’s wide range of experiences and achievements in translational research and inclusive, institutional leadership will be invaluable as BME continues to solve important challenges in medicine and life sciences to the benefit of humanity.

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ANNUAL BME SYMPOSIUM HIGHLIGHTS RESEARCH OPPORTUNITIES STORY BY MICHELE SANTILLAN

The U-M Biomedical Engineering Symposium with Glenn V. Edmonson Lecture is intended to build the BME community across campus and honor the legacy of the first graduate chair of the Biomedical Engineering program. These events provide a forum for BME faculty and students campus-wide, along with our collaborators, to present current research progress and discuss future research opportunities at the interface of engineering and medicine.

The most recent symposium occurred in May 2023 on the U-M North Campus, featuring keynote speaker Naomi Chesler, PhD, Chancellor’s Inclusive Excellence Professor, Department of Biomedical Engineering University of California, Irvine, and the Director of the UC Irvine Edwards Lifesciences Foundation Cardiovascular Innovation & Research Center. Her talk was titled, “An Inclusive Investigation into Pulmonary Hypertension” and highlighted her contributions to research in two main areas: cardiovascular biomechanics and mechanobiology and engineering education.

These yearly activities provide a forum for BME faculty, staff, students and collaborators to share current research progress and discuss future research opportunities at the interface of engineering and medicine.

“I think the event was great for reconnecting people across the broad BME community, and as new faculty I particularly enjoyed getting to hear about diverse research topics from the faculty and students in our department,” said Anne Draelos, U-M BME Assistant Professor of Biomedical Engineering, Assistant Professor of Computational Medicine & Bioinformatics, and Member, Michigan Neuroscience Institute. “Everyone did a

fantastic job presenting their ideas and results through the talks and posters.”

Thanks to the generosity of the Edmonson Family, BME awarded scholarships at the symposium to four graduate students, from our Sequential Undergraduate/Graduate Studies (SUGS) through PhD. Awardees: - Jordan Kamen (Academic excellence; above and beyond GSI expectations; academic researcher, hospital volunteer, and student tutor) - Firaol Midekssa (Academic excellence; exceptional progress in research; undergrad mentor; significant DEI efforts including co-founded program to increase access to graduate school for URM students) - Brian Ross (Academic excellence; undergraduate mentoring and collaboration; GSC leadership; leading multiple exciting research projects) - Fulei Wuchu (Academic excellence; optimized as GSI; mentoring and collaborating in research; active in community service and advocacy).

Watch for information about the 2024 BME Symposium coming in spring.

BME innovations

RESEARCHERS SHARE ADVANCES IN VISION RESEARCH DURING BME SUMMER WORKSHOPS @ MICHIGAN MEETING STORY BY MICHELE SANTILLAN

More than 65 researchers participated in the first BME Summer Workshops @ Michigan meeting on August 11-12. The Biomedical Engineering Department partnered with Ophthalmology and Visual Sciences to cohost the workshop on imaging and therapy in vision research, which featured 25 speakers highlighting their latest research. The smallgroup setting provided a forum for the exchange of technical information, allowing attendees to engage in dialogue with presenters.

“The goal of the BME Summer Workshops @ Michigan series is to establish the University of Michigan in Ann Arbor as a place to gather, learn, and network – each year in the summer, when the weather is so wonderful – on important research topics in BME,” said Mary-Ann Mycek, Professor of Biomedical Engineering and the William and Valerie Hall Department Chair of Biomedical Engineering. “I want to thank our colleagues at U-M Ophthalmology & Visual Sciences in the Kellogg Eye Center for committing to co-host the 2023 workshop with us and for developing the exciting agenda. I am especially grateful to Professors Gary Xu and Xueding Wang for co-organizing this year’s workshop.”

“The speakers did a great job of interacting

with everyone in both departments,“ said Gary Xu, U-M Assistant Professor of Biomedical Engineering and Ophthalmology departments and a co-organizer of the event. “The interaction between the external speakers and internal researchers is very important. When we can talk personally to other researchers, we can gain a greater understanding of different perspectives, helping us all to move forward in our research.”

“I think this event showcases the engineering powerhouse that Michigan really has here,” said Juliette McGregor, Assistant Professor of the Department of Ophthalmology and Visual Sciences at the University of Rochester.

Professor McGregor was one of several invited speakers from outside U-M to present. “There has been material ranging from the genetic modification of new animal models to some of the more sophisticated imaging approaches, and then discussion about robotic-assisted surgery. It’s been great to hear from speakers here as well as invited speakers from around the country. This has really had a workshop feel, where you can try to help each other and share common issues and experiences, in addition to showcasing what you do,” McGregor said.

“The co-organizers did a great job of highlighting outstanding research, both at U-M

and around the country,” said Joseph Izatt, the Michael J. Fitzpatrick Distinguished Professor of Engineering, and Chair of BIomedical Engineering at Duke University, and an invited presenter. “The size of the event was nice,” he added. “I think that the mix of internal research with a few invited outside guest speakers worked out well.”

“I would like to see this as a yearly event for all of us to come together,” said Dorsa Ghaffari, a postdoctoral researcher in the lab of Jim Weiland, U-M Associate Chair for Research in Biomedical Engineering and Professor, Biomedical Engineering and Professor, Ophthalmology and Visual Sciences. ”I like the small-group format because this setting helps you feel more comfortable to ask follow-up questions and interact more with the speakers.”

Jeanpaul Passo, a first-year PhD student who is also in Professor Weiland’s lab, agreed with Ghaffari and added that this exchange of ideas helps researchers approach issues in different ways. “It’s refreshing to see what other lab groups are working on and how they are approaching various topics. The smaller setting also has a community feel, so it’s easier to have your voice heard in the discussion.”

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NETP SYMPOSIUM PROVIDES OPPORTUNITY TO SHARE LATEST ADVANCES STORY BY MICHELE SANTILLAN

U-M’s Neural Engineering Training Program (NETP) provides comprehensive and innovative training opportunities to enhance participants’ graduate school experience. The NETP is creating leaders of the 21st century neural engineering workforce who possess the tools to address formidable challenges that, without solutions, could limit the effectiveness of medical devices designed to restore lost neural function. Research conducted by NETP labs spans from fundamental neuroscience to clinical trials of new therapies.

“The program provides co-curricular activities that enhance student training. For example, our seminar series includes speakers from industry, government, and academia, who utilize their PhD training in these varied roles. NETP students can learn first-hand about career options after graduate school, and how they can best position themselves for these different paths” said James Weiland, U-M BME Associate Chair for Research in Biomedical Engineering (Medical School), Professor,

Biomedical Engineering and Professor, Ophthalmology and Visual Sciences. Dr. Weiland serves as the director of the NETP. NETP is supported by a T32 Institutional Training Grant from the National Institute of Neurological Disorders and Stroke.

Each year, NETP hosts a symposium highlighting research and providing a forum for professional discussion. The 2023 session featured keynote speaker Jen French, Neurotech Development and Community Engagement, Neurotech Network Co-Founder and Principal Consultant.

French described her own personal experiences as a wheelchair user and a recipient of implantable neurotechnology, which allows her to stand despite her severe spinal cord injury. She stressed the importance of involving patients in the early design phase of medical devices.

Stay tuned for information about the spring 2024 NETP Symposium and details on how to participate.

BME innovations

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BM E L AU N C H E S A DVA NCED MEDI C AL P R O DU C T ENGI NE E R I N G A N D DEVELO PMENT (AM P ED) MENG D E GR E E AS A M AST ER ’S O P TI O N U-M BME is excited to launch a new Master of Engineering (MEng) degree designed for those who want to make an impact in the medical technology industry. The Advanced Medical Product Engineering and Development (AMPED) MEng program offers an experiential product realization practicum (design-build-test) with a focus on quality systems, risk management and regulatory structures. It also includes courses on advanced topics in medical product development, as well as professional and leadership development.

This MEng degree is an added option, along with our MS and MSE degrees, as part of our Master’s program. Under the guidance of BME faculty advisors, students plan a course of study in one of five concentrations for the MS and MSE degree options: • Bioelectrics and Neural Engineering • Biomaterials and Regenerative Medicine • Biomedical Imaging and Ultrasonics • Biotechnology and Systems Biology • Biomechanics and Biotransport The first cohort of 25 AMPED MEng students started this fall, and applications for Fall 2024 opened in mid-September. The program is designed to be completed in two to three academic terms, depending on academic background. Successful applicants typically have an undergraduate degree in engineering or the physical sciences and a demonstrated interest in medical product development.

Jan Stegemann, Professor, Biomedical Engineering, serves as the BME MEng Director. For more information about the BME MEng program, visit amped.bme.umich.edu or masters.engin.umich.edu/degree/biomedical-engineering-mse/.

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TUMOR-DESTROYING SOUNDWAVES RECEIVE FDA APPROVAL FOR LIVER TREATMENT IN H UMANS STORY BY JIM LYNCH The U.S. Food and Drug Administration has approved the use of sound waves to break down tumors—a technique called histotripsy—in humans for liver treatment.

Pioneered at the University of Michigan, histotripsy offers a promising alternative to cancer treatments such as surgery, radiation and chemotherapy, which often have significant side effects. Recently, Food and Drug Administration’s (FDA) officials awarded clearance to HistoSonics, a company co-founded in 2009 by U-M engineers and doctors for the use of histotripsy to destroy targeted liver tissue.

A human trial underway since 2021 at the U-M Rogel Cancer Center and other locations has treated patients with primary and metastatic liver tumors via histotripsy, demonstrating the technology’s ability to meet the testing’s primary effectiveness and safety targets.

“Histotripsy is an exciting new technology that, although it is in early stages of clinical use, may provide a non-invasive treatment option for patients with liver cancer. Hopefully, it can be combined with systemic therapies for a synergistic therapeutic effect,” said Mishal Mendiratta-Lala, an assistant professor of radiology with Michigan Medicine and principal investigator on the trial at U-M.

Cavitation caused by soundwaves causes bubble clouds that destroy cancerous cells and tissues

Histosonics can now market and sell its histotripsy delivery platform, called Edison, to hospitals and medical professionals for use in liver treatments. The company is headquartered in Minneapolis, while its advanced research and development is located in Ann Arbor.

Histotripsy works by using targeted ultrasound waves to form microbubbles within the tumor. The forces created as those bubbles form and collapse cause the mass to break apart, killing tumor cells and leaving the debris to be cleaned up by the immune system.

What that could mean for patients is treatment without the physical toll of radiation or chemotherapy, fewer concerns with drug compatibility, far shorter recovery times than with surgery and less treatment discomfort.

This is possible because it is much easier to ensure that histotripsy treatments are hitting the tumor, and not healthy

tissue, compared to radiation or invasive procedures. Histotripsy relies on focusing acoustic waves of high-energy ultrasound to concentrate the energy enough to form bubbles, and the Edison machine can make sure that region is confined to the tumor. In contrast, radiation affects everything in its path through the body.

In addition, the histotripsy system has onboard diagnostic ultrasound imaging, the kind used to see babies in the womb.

It is used to plan and observe the treatment in real time.

Physicians have a live view of the “bubble cloud” and how tissue is responding to the therapy.

And histotripsy’s potential benefits go beyond tumor destruction. In the last year, a pair of pre-clinical studies in rodents suggest that in the clean-up process, the immune system learns how to identify cancer cells as threats. This can

BME innovations enable the body to continue fighting the initial tumor and help activate a natural immune response to the cancer.

In the first study, even after destroying only 50% to 75% of the liver tumor volume by histotripsy, the rats’ immune systems were able to clear away the rest, with no evidence of recurrence or metastases in more than 80% of animals.

Earlier this year, a second study showed that histotripsy breaks down the cancer cell wall’s “cloak”—revealing proteins that the immune system can use to identify threats, known

DISTINGUISHED U N I V E R S I T Y INNOVATOR AWARD The University of Michigan’s 2023 Distinguished University Innovator Award has been given to the university’s histotripsy team, led by several faculty from Michigan Engineering and the Medical School.

Recipients include Professors Zhen Xu, J. Brian Fowlkes, and William Woodruff Roberts, with research scientists Timothy Hall and Jonathan Sukovich. The team was commended for bringing the innovative technique, histotripsy, to clinics for treating human diseases.

The prestigious award recognizes faculty members’ innovative ideas, processes, or technology that have positively impacted society. The histotripsy team, through a simultaneous pursuit of innovative solutions, has created a groundbreaking medical procedure that addresses significant global health challenges.

Zhen Xu, Professor of Biomedical Engineering, Radiology and Neurosurgery, looks on as she explains a histotripsy treatment demonstration. Image credit: Erica Bass, Rogel Cancer Center, Michigan Medicine

as antigens. These antigens are removed during surgery or destroyed during chemotherapy and radiation. By instead destroying a cancer cell’s outer wall, histotripsy lays bare the tumor antigens for the immune system to identify and use for targeted attacks on other cancer cells.

“We want to leverage histotripsy’s immuno stimulation effects and hopefully combine them with immunotherapy or drug delivery,” said Zhen Xu, a U-M professor of Biomedical Engineering, Radiology and Neurosurgery, an inventor of the histotripsy approach and a cofounder of HistoSonics. “That will move histotripsy from a local therapy into one that can treat tumors globally all over the body and eventually into a cure. In terms of the cancer treatment, that will be the next step, and I feel very excited about the potential.”

Mendiratta-Lala, Xu and the University of Michigan have a financial interest in HistoSonics.

The company was formed with support from Innovation Partnerships, U-M’s central hub for research commercialization.

Their startup, HistoSonics, based on histotripsy and launched in 2010, has developed the Edison System, a novel noninvasive procedure that uses sound wave energy to destroy diseased tissue.

This technology mitigates the limitations of earlier versions such as bleeding, infection, and heat-induced complications.

HistoSonics, now employing more than 100 people and raising more than $200 million, offers services positively impacting patients while generating economic impact. The successful commercialization of this invention is, in large part, due to the support from the Innovation Partnerships of the University of Michigan and The Coulter Foundation.

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U-M BM E- L ED STUDY RE VEALS T H E K EY R OL E OF ANTI -TUMO R N EU T R OP H ILS I N SUPPR ESS I N G LU N G METASTAS I S O F BR E AST C ANCER STORY BY MICHELE SANTILLAN

A U-M BME-led study published in Nature Communications on August 8 reveals the multifaceted roles of neutrophils in regulating lung metastasis in breast cancer and underscores the key role of neutrophils with anti-tumor phenotypes in suppressing breast cancer cell growth in the lungs.

This study was led by Dr. Lonnie Shea, the U-M BME Steven A. Goldstein Collegiate Professor of Biomedical Engineering, Professor of Chemical Engineering and Surgery, and Dr. Jacqueline Jeruss, U-M Associate Dean for Regulatory Affairs, Associate Vice President for Research, and professor of surgery, pathology and BME. Dr. Jing Wang, formerly a postdoctoral fellow at U-M BME and currently an assistant professor at Iowa State University, is the first author. Dr. Aaron Morris, U-M BME assistant professor, is a co-author on this work.

T h e re s e a rc h t e a m e m p l o y e d a subcutaneous biomaterial scaffold implant to mimic the immune environment in metastatic organs and deconstruct complex signals regulating metastasis. The scaffold implant in mouse models of metastatic breast cancer creates a synthetic metastatic niche, an environment that can recruit lung-tropic circulating tumor cells (tumor cells that preferentially migrate to the lungs) yet suppress their growth through potent in situ anti-tumor immunity. In contrast, similar circulating tumor cells seed the lungs, the endogenous metastatic organ for these models, and develop into lethal metastatic tumors as the environment in the lungs becomes immunosuppressive and protumor at this stage of breast cancer metastatic progression.

The team examined why scaffolds and lungs in the same mouse create different immune environments and direct opposite fates of metastatic breast cancer cells. They found that the selective recruitment of neutrophils with different phenotypes from the circulation determines that the overall environment in the

scaffold or lungs is immune-stimulatory and anti-tumor or immunosuppressive and protumor, respectively. “Our study indicates that the scaffold implants overproduce chemokines CXCL1, CXCL2, and CXCL5 due to the foreign body responses to scaffold implants.” Dr. Wang said. “And these chemokines recruit anti-tumor neutrophils from the circulation to activate tumor-killing effector cells (CD8+ T cells and NK cells) to clear tumor cells seeding the scaffolds.

In contrast, the lungs in mice with metastatic breast cancer overproduce S100A8/A9 protein complex to recruit pro-tumor neutrophils that suppress the activity of effector cells

and support tumor cell growth.” A scheme is provided in Figure 1.

Additionally, their findings from the synthetic metastatic niche further explain why the lungs from the host with non- or weakly metastatic breast cancers do not develop metastatic tumors. In contrast to the lungs in the setting of metastatic breast cancer that are dominated by pro-tumor neutrophils and deactivated effector cells, the lungs in non- or weakly metastatic breast cancers overproduce CXCL1, CXCL2, and CXCL5, possibly due to immunoediting of primary tumors, to recruit and enrich anti-tumor neutrophils and create an environment with potent anti-tumor immunity that prevents the growth of metastatic cells.

“Our findings have been validated and may have clinical implications. A high ratio of signals that recruit anti-tumor neutrophils (Cxcl1, Cxcl2, or Cxcl5 genes) to signals that recruit pro-tumor neutrophils (S100a8, or S100a9 genes) was positively correlated to a low chance of developing metastasis in our study.

This ratio may help to predict the risk level of lung metastasis for patients with breast cancer.” said Dr. Wang. Dr. Shea added that the scaffolds are being developed for a clinical study, and this ratio could be derived from the scaffold, thereby providing an opportunity to assess metastatic disease and guide patient management without an invasive biopsy of vital organs.

Dr. Wang added: “Our findings also have therapeutic implications, as this mechanistic study will inspire new anti-metastasis therapy strategies directed towards changing the signals in the lungs from those recruiting protumor neutrophils to those recruiting anti-tumor neutrophils.”

Figure 1. Schematic illustration of the selective recruitment of anti-tumor and pro-tumor neutrophils to the lungs of animal models of breast cancers with varying tumor aggressiveness responding to distinct groups of chemokines/cytokines that attract neutrophils, followed by creation of an environment in the lungs that supports or suppresses growth of breast cancer cells.

BME innovations

AI COULD RUN A MILLION MICROBIAL EXPERIMENTS PER YEAR STORY BY JIM LYNCH

An artificial intelligence system enables robots to conduct autonomous scientific experiments—as many as 10,000 per day—potentially driving a drastic leap forward in the pace of discovery in areas from medicine to agriculture to environmental science.

As reported in Nature Microbiology, the team was led by a professor now at the University of Michigan.

That artificial intelligence platform, dubbed BacterAI, mapped the metabolism of two microbes associated with oral health— with no baseline information to start with. Bacteria consume some combination of the 20 amino acids needed to support life, but each species requires specific nutrients to grow. The U-M team wanted to know what amino acids are needed by the beneficial microbes in our mouths so they can promote their growth.

“We know almost nothing about most of the bacteria that influence our health. Understanding how bacteria grow is the first step toward reengineering our microbiome,” said Paul Jensen, U-M Assistant Professor of Biomedical Engineering and Chemical Engineering, who was at the University of Illinois when the project started.

Figuring out the combination of amino acids that bacteria like is tricky, however. Those 20 amino acids yield more than a million possible combinations, just based on whether each amino acid is present or not. Yet BacterAI was able to discover the amino acid requirements for the growth of both Streptococcus gordonii and Streptococcus sanguinis.

To find the right formula for each species, BacterAI tested hundreds of combinations of amino acids per day, honing its focus and changing combinations each morning based on the previous day’s results. Within nine days, it was producing

DR. PAUL JENSEN

accurate predictions 90% of the time.

Unlike conventional approaches that feed labeled data sets into a machine-learning model, BacterAI creates its own data set through a series of experiments. By analyzing the results of previous trials, it comes up with predictions of what new experiments might give it the most information. As a result, it figured out most of the rules for feeding bacteria with fewer than 4,000 experiments.

“When a child learns to walk, they don’t just watch adults walk and then say ‘Ok, I got it,’ stand up, and start walking. They fumble around and do some trial and error first,” Jensen said.

“We wanted our AI agent to take steps and fall down, to come up with its own ideas and make mistakes. Every day, it gets a little better, a little smarter.”

Little to no research has been conducted on roughly 90% of bacteria, and the amount of time and resources needed to learn even basic scientific information about them using conventional methods is daunting. Automated experimentation can drastically speed up these discoveries. The team ran up to 10,000 experiments in a single day.

But the applications go beyond microbiology. Researchers in any field can set up questions as puzzles for AI to solve through this kind of trial and error.

“With the recent explosion of mainstream AI over the last several months, many people are uncertain about what it will bring in the future, both positive and negative,” said Adam Dama, a former engineer in the Jensen Lab and lead author of the study.

“But to me, it’s very clear that focused applications of AI like our project will accelerate everyday research.”

The research was funded by the National Institutes of Health with support from NVIDIA.

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Surgeon uses academic development time to collaborate with BME STORY BY MICHELE SANTILLAN Dr. Drew Braet is a fourth-year resident in Vascular Surgery and is taking his two-year academic development time to work with C. Alberto Figueroa, the Edward B Diethrich M.D. Research Professor of Biomedical Engineering and Vascular Surgery, professor of surgery, Medical School and professor of biomedical engineering, Medical School and College of Engineering. Dr. Braet’s goal from this collaboration is to gain a better understanding of determining which patients are most likely to benefit from surgical intervention.

“I sought to work with Biomedical Engineering, and Dr. Figueroa, specifically, by choice,” Dr. Braet said. “Early in my training, I became frustrated with the lack of information we often have about vascular disease, particularly when looking at which patients we should or should not offer surgery to. It’s pretty typical in medicine that things aren’t black and white, and that there are many gray areas. We’re really lacking clear data in a lot of different realms that can help us with decision making.”

“It is not typical that a surgeon would do research in an engineering laboratory like ours,” said Dr. Figueroa. “To have someone who goes from operating on patients to then spending two years learning analytical tools–imaging tools, modeling tools and computational tools–is somewhat unique.” A two-year research period is mandatory at U-M, but most people in the training program do not end up focusing on Engineering. “Historically, most trainees do time working in a basic science wet laboratory,” he added.

Dr. Braet was researching information in his quest to learn

“

In the big picture, if more surgeons and more doctors learned to look at challenges differently, we might be able to be more creative in the treatments that we can offer.

Dr. Drew Braet M.D. House Officer 4 (ADT), Integrated Vascular Surgery Residency

BME innovations more ways data analysis can inform surgical interventions, and through a Google search, came upon Dr. Figueroa’s lab.

“I thought what he was doing in using computational methods in advanced imaging analysis would really help me,” Dr. Braet said. “I wanted to learn a tool set to be able to explore some of the questions I had. I ultimately want to improve our understanding and to provide better patient care. We met early on in my intern year. I heard about some of the work they were doing in the lab and explained some of the things I was interested in. In my intern year, we started doing a smaller project. Dr. Nick Burris, a radiologist, and I worked on that for a year, and we were able to publish a paper. From there, we started thinking about a bigger project that we could do during my dedicated time, and that led us to do my current project and current NIH F32 fellowship, where I’m looking at patients with high-grade asymptomatic carotid artery disease.”

The carotid artery is the artery in your neck that goes to your brain.

“Patients who have narrowings in that artery have buildup of cholesterol plaque, the same kind of plaque that can lead to heart attacks,” Dr. Braet said. “That plaque can break off, and cause a stroke. The way that we think about these plaques in medicine is based on historical studies which suggest that the percentage of narrowing of the carotid artery is related to the risk of having a stroke. When I think about that from a biophysical and biomechanical standpoint, it doesn’t make sense. Not to discredit the studies that were previously done, this is what science has shown and we have helped a lot of people by thinking that way. But when you really boil it down to the biophysics of blood flow, that doesn’t make sense, because plaques rupture when the forces exerted on them exceed the strength of the tissue. We’re doing a computational modeling study by looking at the pressure differences, the velocity differences and the wall shear stress on carotid artery plaques to try to get a better understanding of the hemodynamic strains and stresses of the plaque and thus the risk of stroke. This could potentially lead to an entirely new way of looking at the way patients present with this particular issue. In a perfect world, 20 years from now, it would be great if the medical field could be using some of the things that we’re studying today. These kinds of engineering, imaging

and modeling analyses, I think, will help us do a much better job with risk stratification that ultimately will determine whether to perform surgery or to watch a patient more conservatively.”

Dr. Braet noted that it is “refreshing” to learn to examine problems in a different way. ”In the big picture, if more surgeons and more doctors learned to look at challenges differently, we might be able to be more creative in the treatments that we can offer,” Dr. Braet said. The analysis of big data and the use of technological innovations are playing increasingly important roles in medicine, and Dr. Braet wants to understand how Engineering can assist the profession.

Dr. Figueroa noted the value of this type of mentorship for the mentor as well as the mentee. “It’s interesting because someone like Drew has a very different background and very different ways of seeing a problem than someone from a traditional engineering background,” he said. “Everybody talks about translation and reaching out, and when you are in engineering, you want to have your tools applied, but it’s actually quite difficult to do because of how distant the training and the day-to-day professional thought processes these two groups have. In engineering, you typically say you want to talk to clinicians because at the end, they are your customers for developing a new device or a new diagnostic procedure. Eventually, they’re going to have to use it and understand it, right?”

The fact that the University of Michigan has a Biomedical Engineering Department that is jointly in both the Medical School and in the College of Engineering enhances these opportunities for collaboration. “There are a lot of institutions out there where perhaps they have a biomedical engineering department, but they don’t have a medical school,” Dr. Figueroa said. “In those institutions, this understanding is much harder to achieve because the engineering folks are kind of isolated and they don’t have ready access to clinical peers.”

Dr. Figueroa added that the opportunity to serve as a mentor is a rewarding experience, professionally and personally. “To me, it’s important that when I one day finish my career, I will have contributed to training a small group of clinicians who have an engineering thought process,” he said.

2023 HUNT MEMORIAL LEC TURE More than 100 faculty, staff, students and family members attended the November 3 Alan J. Hunt Memorial Lecture, featuring Lisa Pruitt, Ph.D. Dr. Pruitt is the Lawrence Talbot Professor of Engineering, and Professor of Mechanical and Bioengineering at UC Berkeley. During the event. BME’s Andrew Putnam, the Robert C. Leland, Jr. and Donna D. Leland Professor, Biomedical Engineering and Cardiovascular Medicine, shared his remembrances of Professor Hunt and presented Dr. Pruitt with a medallion to commemorate her lecture.

VARIOUS MEMBERS OF THE HUNT FAMILY, PHOTOGRAPHED HERE, HAVE ATTENDED EACH YEAR SINCE THE FIRST LECTURE IN 2013.

LISA PRUITT, PHD, IS PICTURED HOLDING THE MEDALLION PRESENTED TO HER BY ANDREW PUTNAM

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CENTURY-OLD QUESTION ON FLUID IN LUNGS ANSWERED STORY BY JIM LYNCH

Pulmonary edema, a buildup of fluid in the lungs that can be fatal, presents a 125-year-old medical puzzle—one that has now been solved by researchers at the University of Michigan and Arts et Métiers ParisTech.

The finding could shed light on the workings of the lung at a time when respiratory infections such as COVID-19 and RSV are filling hospitals.

As the lungs perform their task of taking in oxygen and expelling carbon dioxide, fluid can accumulate in air sacs of certain patients. The fluid can make it harder for the lungs to perform that gas exchange, and at worst it can bring oxygenation levels low enough to cause death.

But for patients who recover from pulmonary edema, we haven’t really known how the fluid is leaving the lungs. It has been established that the fluid is draining to distant parts of the lymph system. What isn’t known is how it gets there.

In 1896, medical doctor and lung anatomist Dr. William Snow Miller discovered that lung air sacs do not have nearby lymphatics. The nearest lymph vessels were more than a tenth of a millimeter away—an epic journey compared to lymphatic system access in much of the rest of the body. And for more than a century, neither Miller nor anyone else has been able to determine how or why fluid from the air sacs can travel that far.

Enter James Grotberg, a U-M professor of biomedical engineering, and Francesco Romano, an associate professor of fluid mechanics at Arts et Métiers ParisTech and a former postdoctoral researcher in Grotberg’s lab.

What drew you to take a look at this long-standing mystery?

Dr. Grotberg: As the pandemic was bringing respiratory disease into global focus, I thought we might find important insights into the pulmonary edema that continues to cause COVID-19 deaths. My expertise spans the intersection of fluid dynamics and engineering as well as human biology and emergency and critical care medicine, so I am well positioned to explore this problem. Meanwhile, Francesco excels at computational fluid dynamic models, so we teamed up to develop a model for pulmonary edema with support from the National Institutes of Health.

How did you go about solving this?

JAMES GROTBERG

Dr. Grotberg: Since no one had done this before, we started with fundamental flow physics and physiology. The fluid is serum leaking from the blood vessels into the air sacs—that’s pulmonary edema. Meanwhile, the lymphatic system acts like a vacuum, drawing excess fluid out of the tissues. But the lymphatics were far away, too far for their suction to be effective. Given that problem set-up, we used mathematical modeling to simulate both how pulmonary edema builds up and how the body clears it.

What did you find?

Dr. Grotberg: Our model revealed a mechanism that can drive excess fluid from the air sacs to these distant lymphatics. It’s a new physiological flow. We discovered that fluid pressures in the tiny region between air sacs and capillaries is quite different from medical physiology textbook assumptions, and those pressure differences can drive fluid toward the lymphatic system.

How do you think this information can be useful going forward for treating pulmonary edema?

Dr. Grotberg: Any set of concepts underlying diagnosis and therapy has to include all the relevant phenomena. The new flow we discovered is a key ingredient. We believe it’s relevant to both major causes of pulmonary edema: elevated lung blood pressure, a symptom of congestive heart failure, and the breakdown of the air-blood barrier as can occur with infections like COVID-19 and RSV. In both scenarios, excess fluid in the air sacs blocks normal oxygenation and can be lethal.

We hope that our model can provide insights on how to treat pulmonary edema. It takes as inputs the anatomical and physiological parameter values of the lung, as well as clinical interventions, and then simulates how the entire system works.

For instance, an essential component of therapy may be treating the infection with antimicrobial agents—but also keeping the fluid balance well tuned to remove the excess fluid and restore normal oxygen delivery. Our model can predict how the fluid levels in the lungs will respond to changing conditions.

In the study report, we present several more scenarios to which our model may be applied, so the field has new doorways available for investigation. It will be interesting to see how this propagates.

BME innovations

ST U DY FINDS E X H AL ED BREATH COULD ENHA N CE DE T E C T I O N , D IAGN OSIS OF COV I D-1 9 A ND VARIANTS STORY BY JIM LYNCH Research suggests volatile organic compounds in breath could mark distinction between COVID-19, variants and non-COVID illnesses The emergence of new COVID-19 variants has led to reduced accuracy across current rapid testing methods, but a recent University of Michigan study suggests that a patient’s breath might hold the key to a more precise diagnosis.

Investigators from the University of Michigan’s Max Harry Weil Institute for Critical Care Research and Innovation, including faculty and students from the College of Engineering and Michigan Medicine, used portable gas chromatography to examine breath samples collected during the pandemic’s Delta surge and its transition to Omicron (from April 2021 to May 2022.)

Their results, published February 28 in JAMA Network Open, showed that the GC technology could diagnose COVID-19 with a high level of accuracy. They also revealed that the volatile organic compounds contained in the breath of patients with Omicron differed from those in patients with Delta and earlier variants—molecular-level differences which, according to the team, could potentially be used to distinguish between COVID-19, its variants and non-COVID illnesses.

“Exhaled breath contains hundreds of VOCs, which the body produces in response to infection and inflammation,” said principal investigator and study author Xudong (Sherman) Fan, Ph.D., Richard A. Auhll Endowed Professor of Biomedical Engineering and associate director of the Weil Institute. “Early in the pandemic, we used GC technology to discover and define sets of VOCs for detecting COVID-19. However, we needed to gain a better understanding of how dynamically emerging variants impact this technology.”

Supported by a $2 million grant from the National Institutes of Health Rapid Acceleration of Diagnostics initiative’s Screening for COVID-19

by Electronic-Nose Technology program, the

team conducted a diagnostic study of 167 adult patients in the Michigan Medicine ICUs and emergency department. They collected 205 breath samples from symptomatic and asymptomatic patients in 3 cohorts: · COVID-19 (2021): Patients with COVID-19 who were recruited before December 14, 2021, and were assumed to be infected by the Delta or earlier variants · COVID-19 (2022): Patients with COVID-19 who were recruited from January 2022 to the end of May 2022 and were assumed to be infected by the Omicron variant · Non-COVID-19 illness: Patients who were COVID-19 negative at the time of breath analysis, as well as patients who were previously COVID-19 positive but had recovered Using a novel point-of-care GC device developed by Fan and the team, in combination with an advanced biomarker discovery algorithm and data analysis platform developed at the College of Engineering and the Weil Institute, the investigators defined four sets of VOCs that were able to distinguish between COVID-19 (2021) and non-COVID illness with a sensitivity of 92.7%, a specificity of 95.5% and an accuracy of 94.7%. However, when the team applied the same VOCs in a setting of presumed Omicron, sensitivity decreased drastically to 60.4%.

“We already knew clinically that different strains of SARS-CoV-2 can act quite differently,” said study co-author Robert Dickson, M.D., associate professor of Pulmonary and Critical Care Medicine and deputy director of the Weil Institute. “This decrease in performance supports our suspicion that their effects on lung biology are quite different as well.”

Based on their findings, the team hypothesized that it could be possible to use breath analysis to distinguish between COVID

variants. They undertook additional biomarker searches and defined new VOCs to discern between Omicron and Delta, Omicron and non-COVID illness, and between patients with COVID-19 and non-COVID illness regardless of variants. The combined analysis resulted in the ability to detect COVID-19-infected patients (regardless of variant) from non-COVID patients with a sensitivity of 89.4%, a specificity of 91.0% and an accuracy of 90.2%. This performance is close to that of RT-PCR tests (the gold standard) and better than many rapid antigen tests.

Co-author and co-principal investigator Kevin Ward, M.D., professor of Emergency Medicine and Biomedical Engineering and executive director of the Weil Institute said, “This work suggests that breath analysis using point-of-care GC may be a promising method for detecting COVID-19 and similar diseases that result in VOC production. However, as we are seeing with other detection and testing methods, the emergence of viral variants continues to pose challenges.” The team notes that further analysis will be needed to determine how to overcome these challenges and use breath analysis to improve the diagnosis and care of patients.

“The fact that we were able to diagnose C OV I D -1 9 i n b ot h sy m pto m at i c a n d asymptomatic participants is encouraging,” said Fan. “More studies on these particular VOCs, including their origins, may assist in the development of a better understanding of COVID-19 as well as the potential to develop new diagnostics.”

“Looking ahead, our diagnostic approach to COVID-19 and the lung injury it causes will need to be as dynamic as the virus itself,” said Dickson.

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Shutting down backup genes leads to cancer remission, in mice

STORY BY JIM LYNCH

Cancer cells delete DNA when they go to the dark side, so a team of doctors and engineers targeted the “backup plans” running critical cell functions.

The way that tumor cells enable their uncontrolled growth is also a weakness that can be harnessed to treat cancer, researchers at the University of Michigan and Indiana University have shown. Their machine-learning algorithm can identify backup genes that only tumor cells are using so that drugs can target cancer precisely.

The team demonstrated this new precision medicine approach treating ovarian cancer in mice. Moreover, the cellular behavior that exposes these vulnerabilities is common across most forms of cancer, meaning the algorithms could provide better treatment plans for a host of malignancies.

“This could revolutionize the precision medicine field because the drug targeting will only affect and kill cancer cells and spare

the normal cells,” said Deepak Nagrath, a U-M professor of biomedical engineering and senior author of the study in Nature Metabolism. “Most cancer drugs affect normal tissues and cells.

However, our strategy allows specific targeting of cancer cells.”

This approach is known as collateral lethality—using information gleaned from genes that cancer cells discard to find weaknesses. The human body comes with many mechanisms designed to protect against cancer. Cancer cells themselves used to contain suppressor genes that prevent their spread. Those cells, however, have a clever strategy for dealing with that; they simply delete a portion of their DNA—the part that includes those suppressor genes.

In doing so, the cells typically lose other genes that are necessary for survival. To avoid death, the cells find a paralog—a gene that can serve a similar function. Usually, there are one or, possibly, two genes that can step in and perform the same function to keep the cell alive.

What if you could identify the right paralog and target it in a way that shuts down its vital function for the cell?

“When a direct replacement for the deleted metabolic gene is not available, our algorithms use a mathematical model of the cancer cells’ metabolism to predict the paralogous metabolic pathway they might use,” said Abhinav Achreja, a U-M research fellow in biomedical engineering and lead author on the research paper. “These metabolic pathways are important to the cancer cells and can be targeted selectively.”

Attacking metabolic pathways essentially shuts down the cell’s energy source. In examining ovarian cancer cells, U-M’s team zeroed in on one gene, UQCR11, that was often deleted along with a suppressor gene. UQCR11 plays a vital role in cell respiration—how cells break down glucose for energy in order to survive.

Disturbances in this process can lead to a major imbalance of an important metabolite, NAD+, in the mitochondria, where respiration takes place. Despite all odds, ovarian cancer cells continue to thrive by relying on their backup plan.

U-M’s algorithm correctly sorted through multiple options and successfully predicted a cell missing UQCR11 would turn to the gene MTHFD2 as its backup supplier of NAD+.

Researchers at the Indiana University School of Medicine helped validate the findings in the lab. This team, led by professor of medicine Xiongbin Lu, developed genetically modified cell and animal models of ovarian cancers with deletions. Six out of six mice tested showed complete cancer remission.

This research was supported by funding from the National Cancer Institute, the Office of the Director for the National Institutes of Health, the University of Michigan Precision Health Scholars Award, and Forbes Scholar Award from Forbes Institute of Cancer Discovery.

BME innovations

TRACKING RADIATION TREATMENT IN REAL TIME PROMISES SAFER, MORE EFFECTIVE CANCER THERAPY STORY BY JIM LYNCH

Radiation, used to treat half of all cancer patients, can be measured during treatment for the first time with precise 3D imaging developed at the University of Michigan.

By capturing and amplifying tiny sound waves created when X-rays heat tissues in the body, medical professionals can map the radiation dose within the body, giving them new data to guide treatments in real time. It’s a firstof-its-kind view of an interaction doctors have previously been unable to “see.”

“Once you start delivering radiation, the body is pretty much a black box,” said Xueding Wang, the Jonathan Rubin Collegiate Professor of Biomedical Engineering, professor of radiology and corresponding author of the study in Nature Biotechnology. He also leads U-M’s Optical Imaging Laboratory.

“We don’t know exactly where the X-rays are hitting inside the body, and we don’t know how much radiation we’re delivering to the target. And each body is different, so making predictions for both aspects is tricky.”

Radiation is used in treatment for hundreds of thousands of cancer patients each year, bombarding an area of the body with high energy waves and particles, usually X-rays. The radiation can kill cancer cells outright or damage them so that they can’t spread.

These benefits are undermined by a lack of

precision, as radiation treatment often kills and damages healthy cells in the areas surrounding a tumor. It can also raise the risk of developing new cancers.

With real-time 3D imaging, doctors can more accurately direct the radiation toward cancerous cells and limit the exposure of adjacent tissues. To do that, they simply need to “listen.”

When X-rays are absorbed by tissues in the body, they are turned into thermal energy. That heating causes the tissue to expand rapidly, and that expansion creates a sound wave.

The acoustic wave is weak and usually undetectable by typical ultrasound technology.

U-M’s new ionizing radiation acoustic imaging system detects the wave with an array of ultrasonic transducers positioned on the patient’s side. The signal is amplified and then transferred into an ultrasound device for image reconstruction.

With the images in-hand, an oncology clinic can alter the level or trajectory of radiation during the process to ensure safer and more effective treatments.

“In the future, we could use the imaging information to compensate for uncertainties that arise from positioning, organ motion and anatomical variation during radiation therapy,” said Wei Zhang, a research investigator in

biomedical engineering and the study’s first author. “That would allow us to deliver the dose to the cancer tumor with pinpoint accuracy.”

Another benefit of U-M’s technology is it can be easily added to current radiation therapy equipment without drastically changing the processes that clinicians are used to.

“In future applications, this technology can be used to personalize and adapt each radiation treatment to assure normal tissues are kept to a safe dose and that the tumor receives the dose intended,” said Kyle Cuneo, associate professor of radiation oncology at Michigan Medicine.

“This technology would be especially beneficial in situations where the target is adjacent to radiation sensitive organs such as the small bowel or stomach.”

The research team is led by U-M, including Wang, Cuneo and Issam El Naqa, adjunct professor of radiation oncology at the U-M Medical School. The team works with partners at the Moffitt Cancer Center.

The University of Michigan has applied for patent protection and is seeking partners to help bring the technology to market. The research was supported by the National Cancer Institute and the Michigan Institute for Clinical and Health Research.

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NEW FACULTY MARÍA CORONEL

Assistant Professor, Biomedical Engineering Dr. María Coronel received her BS degree in Biomedical Engineering from the University of Miami, and her PhD in Biomedical Engineering from the University of Florida. She also obtained a certificate in Clinical Translational Research from Emory University Public Health School.

She finished her postdoctoral fellowship at the Georgia Institute of Technology, where she received funding from the Juvenile Diabetes Research Foundation, NIH T31, and Georgia CTSA to support her training.

Her research group focuses on synergizing concepts of biomaterials, tissue engineering, drug delivery and immunoengineering to create synthetic bioactive therapeutics for the treatment of autoimmunity, inflammation and cancer.

ANNE DRAELOS

JONATHAN FAY

Assistant Professor, Biomedical Engineering Assistant Professor, Computational Medicine & Bioinformatics Member, Michigan Neuroscience Institute

Associate Professor of Practice, Biomedical Engineering

Dr. Anne Draelos first studied physics and computer science as an undergraduate at North Carolina State University. She completed a Master’s in Electrical & Computer Engineering and a PhD in physics at Duke University, focused on the interplay between various quantum phenomena in networked systems.

She then cross-trained as a postdoctoral fellow in neuroscience to study arguably the most complex network around: the brain.

Now at U-M BME as faculty, her lab is focused on machine learning and statistical techniques to facilitate real-time analysis of high-dimensional neural and behavioral data.

Dr. Draelos currently holds a Career Award at the Scientific Interface from the Burroughs Wellcome Fund.

Dr. Jonathan Fay received his BS from the University of Notre Dame and his MS and PhD degrees from Stanford University. His research interests focus on how educational interventions and social networks influence the entrepreneurial mindset and subsequent technology diffusion and commercialization.

His lab studies the interplay of how social networks, technology advancements, and business practices lead to the adoption of certain technologies but not others. Most previous research has focused on the attributes of the individual innovators or the technology itself and tries to assess which factors are most important for driving adoption. However, the history of innovation is littered with examples of chance meetings, disparate ideas coming together, and of nearly simultaneous invention by several groups.

Future research will explore the development of high trust social networks, how that impacts the success of innovators and how that influences the diversity of innovators as well as the effectiveness of interventions to address these issues.

BME innovations

KARIN JENSEN

Assistant Professor, Biomedical Engineering Dr. Karin Jensen comes to us from the University of Illinois at Urbana-Champaign and earned a bachelor’s degree in biological engineering from Cornell University and a PhD in biomedical engineering from the University of Virginia. Her doctoral dissertation focuses on “Systems pharmacology of cell-signaling networks in human disease.”

Her research interests include student mental health and wellness, engineering student career pathways, and engagement of engineering faculty in engineering education research. She was awarded a CAREER award from the National Science Foundation for her research on undergraduate mental health in engineering programs. She serves as an associate editor of the Journal of Women and Minorities in Science and Engineering.

PAUL JENSEN

Assistant Professor, Biomedical Engineering Assistant Professor, Chemical Engineering Dr. Paul Jensen was previously an assistant professor at the University of Illinois at UrbanaChampaign and earned bachelor’s degrees in chemical and biomedical engineering from the University of Minnesota and a PhD in biomedical engineering from the University of Virginia. He completed a postdoctoral research fellowship in the Biology Department at Boston College.

His research group studies the oral microbiome using artificial intelligence, laboratory automation, and high-throughput genomics. Dr. Jensen is also interested in educational barriers to careers in artificial intelligence. He serves as co-founder and scientific advisor for Cerillo, LLC, maker of laboratory instrumentation with the biological researcher in mind.

JIAHE LI

Assistant Professor, Biomedical Engineering Dr. Jiahe Li was an assistant professor at Northeastern University’s bioengineering department before coming to U-M BME. He completed his BS in Microbiology at China Agricultural University, Beijing, China and received his Ph.D. in Biomedical Engineering from Cornell University. Dr. Li completed his postdoctoral research at the Massachusetts Institute of Technology as a David Koch Quinquennial Postdoctoral Fellow in the Koch Institute for Integrative Cancer Research.

The Li research group focuses on the development of molecular and live cell-based therapeutics, with a major emphasis on the use of bioconjugation chemistry, synthetic biology, and microbiology to interrogate and manipulate interactions between therapeutics, the microbiome and host. Since starting as an assistant professor in 2019, his group has published 17 papers and filed three patents.

Two inventions in his lab have led to sponsored research agreements with biotech companies to accelerate the bacterial engineering technologies for commercialization.

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NEW FACULTY ENRICO OPRI

KATHLEEN PANAGIS

Assistant Professor, Biomedical Engineering

Assistant Professor, Biomedical Engineering

Lecturer III, Biomedical Engineering

Dr. Aaron Morris completed a BS in BME at Georgia Tech, followed by a PhD in BME from Yale University. As a postdoctoral fellow, Dr. Morris worked with Dr. Lonnie Shea at the University of Michigan to use biomaterials to interrogate the immune system during autoimmunity and with Dr. Joshua Leonard at Northwestern University to build synthetic, modular receptor systems for synthetic biology platforms.

Dr. Morris heads the PRecision Immune MicroEnvironments (PRIME) Lab, which works at the intersection of biomaterials engineering, immunology, and drug delivery. The PRIME lab focuses on using engineered materials as platforms to: study immunology, diagnose disease, and develop therapeutics. They are interested in the interface between materials and living systems, and their long-term vision is to develop non-invasive systems for monitoring and manipulating immunity within tissues.

Dr. Enrico Opri completed his BS and MS degrees in biomedical engineering at Politecnico di Milano and his MS and PhD degrees in biomedical engineering at University of Florida. He completed his postdoctoral fellowship at Emory University in the Neurology Department. His work has been supported by the APDA postdoctoral fellowship, NIH Udall Pilot, NIH T32, and MNI-BI 2022 Neuroregeneration and Cognition.

His lab focuses on the exploration of the neurophysiological activity in the basal gangliathalamocortical circuits in humans affected by neurological disorders (such as Parkinson’s, Tourette’s, Essential Tremor, Epilepsy), while investigating how neuromodulation (e.g. Deep Brain Stimulation, cortical stimulation mapping) alters these networks to bring a therapeutic benefit. His lab aims to identify neurological biomarkers that can be leveraged to strengthen the current clinical procedures employed for the treatment of neurological disorders, including advancements in closed-loop neurostimulation.

Dr. Kathleen Panagis has a BS in Bioelectrical Engineering from Marquette University and MS and PhD degrees in Biomedical Engineering from U-M. Her previous roles at Michigan include a postdoctoral research fellow in the Department of Radiology and a Lecturer I in Biomedical Engineering. Dr. Panagis’ research background is in quantitative magnetic resonance imaging (MRI). As a Lecturer, she will focus on teaching courses in bioelectronics and engineering design.

Dr. Panagis strives to make engineering courses approachable and welcoming. She uses active learning strategies in the classroom and encourages students to develop problemsolving skills and an engineering mindset.

AARON MORRIS

BME innovations

ALEXANDRA PIOTROWSKI-DASPIT

Assistant Professor, Biomedical Engineering Assistant Professor, Internal Medicine - Pulmonary and Critical Care Medicine Division Dr. Piotrowski-Daspit has an SB in ChemicalBiological Engineering and Biology from the Massachusetts Institute of Technology (MIT) and master’s and PhD degrees in Chemical and Biological Engineering from Princeton University. She also trained as a Postdoctoral Fellow in Biomedical Engineering at Yale University.

Her laboratory will focus on engineering polymeric nanoparticles for nucleic acid delivery to the lungs, taking advantage of combinatorial polymer vehicle libraries, high-throughput in vivo screening tools, and three-dimensional cell culture models that recapitulate disease physiology. The goal is to elucidate the structure-function relationships that drive the interactions between nanomedicines and the biological barriers they encounter when administered in vivo at the organism, tissue, and cell levels. Ultimately, this work will contribute to the rational design of delivery vehicles for specific disease targets and aid in the clinical translation of therapeutics.

The technology-driven approach will be applicable to the treatment of many hereditary diseases, with an initial focus on cystic fibrosis (CF).

CONNIE WU

ALISON VANDER ROEST

Assistant Professor, Biomedical Engineering Research Assistant Professor, Life Sciences Institute Assistant Professor, Pharmaceutical Sciences

Assistant Professor, Biomedical Engineering

The Wu lab integrates bioanalytical chemistry, materials engineering and biomolecular engineering approaches to develop diagnostic and therapeutic platforms, including engineered multifunctional RNA therapeutics and ultrasensitive single-molecule detection technologies.

Dr. Wu obtained her B.S. in chemical engineering from Yale University and pursued her Ph.D. in chemical engineering at MIT, where she engineered small interfering RNA (siRNA) delivery systems via nucleic acid engineering and polymer chemistry approaches. Following her graduate studies, she transitioned to the diagnostics field for her postdoctoral research at Brigham and Women’s Hospital and the Wyss Institute at Harvard University, where she pioneered ultrasensitive single-molecule protein detection methods and translated these platforms towards the discovery of rare circulating cancer biomarkers. Dr. Wu is a Biological Sciences Scholar at U-M and is the first joint appointment between the Life Sciences Institute and the College of Engineering.

Alison S. Vander Roest is an assistant professor in Biomedical Engineering at the University of Michigan with a research focus on cardiac mechanobiology. Dr. Vander Roest is originally from Texas and received degrees in Biomedical Engineering from the University of Virginia and Vanderbilt University. Her postdoctoral work at Stanford University focused on using gene edited stem cell derived cardiomyocytes in micropatterned environments to measure the impact of disease causing mutations.

Her K99/R00 funded project will continue in her independent work using multiscale computational modeling approaches to relate cardiac mechanics from the molecular to the cellular/multicellular scale and study the impact of cardiac fibrosis.

Her research interests are in the field of cardiac mechanobiology, seeking to understand how the mechanical environment in the heart influences cell behavior and cardiac function throughout pediatric development and disease.

Her lab uses gene-edited human stem cellderived in vitro systems, and computational models to study disease and potential therapeutics to improve precision medicine.

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SRIRAM CHANDRASEKARAN RECEIVES RESEARCH SCOUT GRANT STORY BY MICHELE SANTILLAN

Next Generation Drug Discovery: Looking Beyond Canonical Drugs Using Mechanistic AI U-M BME’s Sriram Chandrasekaran, Associate Professor of Biomedical Engineering, has a research project being funded

by Research Scouts.

Research Scouts is an agile, low-burden funding program from the Office of Research in the U-M Medical School which gives money to scientists (the “Scouts”) to invest in other scientists’ bold ideas. It’s an investment in the “Bold Science” objective of Michigan Medicine’s research strategic plan, “Great Minds, Greater Discoveries,” and is modeled on the Hypothesis Fund.

The goals of the program are to: ·Spark new scientific conversations and connections ·Unleash the creativity of our scientists ·Test bold ideas that may otherwise go unexplored ·Have fun while facilitating new lines of investigation ·From diverse disciplines across the Medical School, Research Scouts are given funding and are empowered and motivated to support their fellow researchers’ bold ideas. Scouts are searching for early-stage ideas that can transform our current understanding of a scientific concept or field, challenge common dogma, or are wildly new and imaginative.

“With $150k to invest, I wanted to fund Mars Shots – ideas that are a little out there and would never be funded by NIH but, if successful, could be game changers for Michigan Medicine and beyond,” says Peter Scott, Professor of Radiology and a Research Scout.

Dr. Chandrasekaran’s lab examines ways that AI can be integrated into biomedical engineering research. “I was thinking through what the big medical challenges might be 25 years from now in my field, and I thought about the future of drug discovery and how the treatment of diseases such as cancer or infectious disease might change,” he said. “Clinicians are trying to use multiple types of treatment, not just drugs, but they are also giving their patients new immune therapies or changing their diets. During the last decade, there are different types of new treatments that people are exploring. For example, people use microbiome treatment and natural products. You can compare that to traditional drug treatments, and even combine them to see how they work well together.”

Dr. Chandrasekaran’s formal Research Scout proposal says that by the year 2050, society may lose 50 million people a year to climate-change-associated health emergencies, such as the spread of drug-resistant pathogens. Suboptimal diet, lifestyle,

DR. SRIRAM CHANDRASEKARAN and pollution will significantly dampen people’s immunity, while accelerating the spread of infections and immune disorders.

Importantly, the pace of drug discovery has not kept up with the rapid emergence of these diseases.

Future treatments for complex diseases such as cancer and drug-resistant infections will likely involve a combination of multiple therapeutic modalities targeting immunological and metabolic processes. Yet researchers lack a rational basis to design such multimodal treatments. For example, how should precision diets be designed to potentiate immunotherapies or antibiotics?

To address this challenge, Dr. Chandrasekaran proposes developing integrative models that bridge cutting-edge simulation tools from various biomedical domains. His team will utilize hybrid AI methods to integrate mechanistic biochemical models and machine learning to impact a wide range of biological fields.

Dr. Chandrasekaran noted that the use of AI algorithms tackles issues without traditional knowledge or bias. The AI algorithm recommends solutions purely based on the data present, not with preconceived ideas of the way processes or products may have traditionally worked.

“Machine-learning algorithms can find the best way to combine different modalities, such as how you combine changes in metabolism or integrate a drug treatment,” he said. “We are trying to put completely different things together using AI to find the best treatment or combination of treatments to produce the best outcome.”

Scott thinks Dr. Chandrasekaran’s idea to use Artificial Intelligence to revolutionize drug discovery is one such “Mars Shot.”

“The idea of combining multiple therapies with environmental factors such as diet and lifestyle is the foundation of Precision Health,” Dr. Scott observes. Although the data exists, we currently lack a rational basis to design such individualized therapies.

“Sriram’s proposal to use neural networks and high-throughput experimentation to crunch the data and identify multimodal therapies for the most complex diseases facing our patients was a light-bulb moment,” Dr. Scott notes. “If his lab is successful, it could cause a paradigm shift for drug discovery. I’m excited to see what they come up with!”

BME innovations

BIOSCIENCES INITIATIVE COORDINATES COLLABORATION AMONG U-M RESEARCHERS

DR. DAVID KOHN

STORY BY MICHELE SANTILLAN U-M’s Biosciences Initiative (BSI) helps provide the funding and coordination necessary to foster interdisciplinary connections among U-M departments. BSI helps provide the funding and organization that integrate university resources to make U-M a leader in specific areas of the biosciences.

One such area is regenerative medicine.

David Kohn, U-M Professor, Biomedical Engineering; Professor, Dentistry; and the Natalie C. Roberts Endowed Professor, Departments of Biologic and Materials Sciences and Biomedical Engineering, oversees U-M’s BSI in Programmable Biomaterials for Regenerative Medicine.

Dr. Kohn also serves as the Director, Michigan-PittsburghWyss Regenerative Medicine Resource Center; Director of an NIH training program in tissue engineering and regenerative medicine, and is Past President, Society for Biomaterials. He recently was honored by the Biomedical Engineering Society, which named him a BMES Fellow in recognition of his years of distinguished scientific contributions and leadership.

With Dr. Kohn’s guidance, U-M’s Scientific Research Initiative (SRI), Engineering Cell Programmable Biomaterials for Dental and Musculoskeletal Health, seeks to synergize the strengths of biology and engineering in regenerative medicine, with an eye on clinical needs. The program’s mission focuses on the goal to develop materials based in a comprehensive understanding of cellular organization and tissue-formation dynamics.

“One of the primary things we want to accomplish is providing a rational basis for developing materials,” Dr. Kohn said. “And that basis really comes from understanding how cells organize, and how tissues are formed in time and in space.” While the development of new biomaterials is crucial, Dr. Kohn’s vision extends beyond their fabrication. He envisions a new generation of materials that actively interact with their physiological environment, possessing the ability to sense, respond, and adapt, seamlessly integrating therapeutic, diagnostic, and sensing functionalities. Other BME faculty involved in steering the direction of this BSI include Lonnie Shea and Jan Stegemann.

Central to the program’s cross-functional efforts is an annual Grand Challenge event, which is a competition created by the

Programmable Biomaterials Initiative to stimulate innovative research by funding interdisciplinary teams that have not previously collaborated who propose groundbreaking solutions to unsolved problems.

In 2022, the inaugural Grand Challenge successfully funded several new teams that united to address pressing problems.

Aaron Morris, Assistant Professor, Biomedical Engineering, led one group that developed cell-based sensors that can sense inflammation versus regeneration, a technology with the potential to discern between beneficial tissue regeneration and harmful inflammation. A second team, which included BME Associate Professor Brendon Baker is developing ways of integrating microvascularized grafts with host vasculature by using programmable hydrogel composites.

The Michigan-Pittsburgh-Wyss Regenerative Medicine Resource Center, is one of two national centers sponsored by the NIH to accelerate the clinical adoption of regenerative technologies. Under Dr. Kohn’s direction, the center has coalesced expertise and resources to shepherd technologies towards FDA submissions and commercialization. This program, which includes BME faculty Jan Stegemann, is a model that can be translatable and scaled in other clinical therapeutic domains.

Training and education is also a main component of the regenerative medicine infrastructure at U-M. The NIH training program is the longest running NIH-supported training program on campus, starting in 1976. Dr. Kohn has led this program since 2012. Many BME faculty serve as mentors and over 50 BME Ph.D. students have had their careers catalyzed through support by this program.

Dr. Kohn stressed the significance of key hire decisions, collaboration, and integration. He noted that the BSI program recently brought Maria Coronel, Assistant Professor, Biomedical Engineering, onto the team. Her expertise is in “smart materials” that can modulate immune responses and sense and treat diseases. The BSI program is also in the process of conducting searches for the next two hires to further bolster its capabilities.

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BME researchers receive two NIH grants to focus on vision loss, prostate cancer detection STORY BY MICHELE SANTILLAN

DR. XUEDING WANG BME researchers have recently received funding to examine Multimodal Molecular Imaging in vision-loss detection and the clinical translation of dual-modality transrectal ultrasound and photoacoustic imaging for detection of aggressive human prostate cancer. The first project, which runs for four years, is funded by a $2.5M grant from the National Eye Institutes of NIH. The second project is funded for five years by the National Cancer Institute of NIH and is worth approximately $3.5M.

Multimodal molecular imaging of choroidal neovascularization Wet age-related macular degeneration (AMD) is the leading cause of irreversible blindness in the developed world. Choroidal neovascularization (CNV) is the leading cause of vision loss due to AMD. Although anti-vascular endothelial growth factor (VEGF) therapy has shown a great breakthrough in CNV treatment, persistent disease activity (PDA) is common.

U-M BME researchers have developed a high resolution, multimodal ophthalmic imaging system incorporating photoacoustic microscopy (PAM), optical coherence tomography (OCT), and fluorescence microscopy (FM). Chain-like gold nanoparticle clusters have been developed and used to enhance molecular imaging and target integrins present in CNV. The researchers have also developed a robust animal model of PDA using older rabbits that demonstrate minimal response to anti-VEGF therapy. Encouraged by these preliminary results, the research team proposes to further develop this platform molecular imaging technology for AMD with a central hypothesis that a multimodal molecular imaging system that can evaluate the CNV animal model could contribute to understanding the fundamental biology of AMD and the development of new pharmaceutical therapies to treat CNV. While AMD is a serious problem, one critical barrier limiting the ability to test novel therapies in preclinical settings is the lack of CNV animal models with PDA and the lack of methods for longitudinal monitoring of disease biomarkers and response to therapy. The goal of this project is to develop state-ofthe-art multimodal molecular imaging for non-invasive and longitudinal assessment of the imaging biomarkers in a new CNV rabbit model with PDA to offer a platform technology for the development of novel therapeutics.

The lead PIs are Yannis Mantas Paulus, MD, Associate Professor, Ophthalmology and Visual Sciences and Associate Professor, Biomedical Engineering at U-M; and Xueding Wang, the U-M BME Jonathan Rubin Collegiate Professor, Department of Biomedical Engineering and Department of Radiology, and Director of Optical Imaging Laboratory.

“AMD is a common problem in senior citizens, so this is a very big issue,” Dr. Wang said. “In order to understand this clinical condition, we have some imaging technologies already, such as OCT, which stands for optical coherence tomography.

Traditionally, diseases such as AMD, which is a common problem associated with overgrowth of blood vessels called neovascularization, can only be diagnosed at a relatively late stage, often leading to irreversible damage. That’s too late. So we are working to see if some imaging technology, by detecting the molecular biomarkers of the disease, can lead to earlier diagnosis to ensure more effective treatment.”

Dr. Wang explained that this new imaging method offers great sensitivity in detecting molecular biomarkers by leveraging the contrast enhancement made possible by nano-sized gold particles. “We are able to detect the disease at a very early stage and we can see the particular molecular changes,” Dr. Wang said. “This method allows us not to rely on the tissue to change structures before we can detect the disease progression. A company called IMRA, a local company affiliated with Toyota, is building the nanoparticles in collaboration with us,” Dr. Wang said.

BME innovations

“BME and Ophthalmology have been working together for many years,” Dr Wang added. “We have many joint projects, and this is just one example of the successful collaboration between BME and Ophthalmology,”

Clinical translation of dual-modality transrectal ultrasound and photoacoustic imaging for detection of aggressive human prostate cancer The second grant on which Dr. Wang is a PI is worth approximately $3.5 million over five years and focuses on the clinical translation of dual-modality transrectal ultrasound and photoacoustic imaging for the detection of aggressive human prostate cancer. The other PI of this multi-PI project is Dr. Raj Kothapalli, a professor at Pennsylvania State University.

Prostate cancer (PCa), with an annually increasing incident rate, has become the most commonly diagnosed cancer in American men. The accurate diagnosis of aggressive PCa is critical for the survival of patients. Transrectal-ultrasound-(TRUS)guided biopsy, the current standard procedure for evaluating the presence and aggressiveness of PCa, suffers from low core yield, leading to under-sampling and under-grading of clinically significant tumors. To fill this long-standing and serious technical gap in PCa diagnosis, Dr. Wang and Dr. Kothapalli propose to develop a novel dual-modality imaging platform which integrates the emerging photoacoustic (PA) molecular imaging technique with the established TRUS for improved detection and differentiation of clinically significant PCa tumors.

With the unique capability to map functional, chemical, and molecular information reflecting pathological conditions over the entire human prostate in vivo, non-invasively, the proposed TRUS and PA (namely TRUSPA) imaging can sensitively detect spatially distributed tumors and, more importantly, differentiate aggressive versus non-aggressive PCa tumors.

This proposed multi-institutional research will leverage the extensive experience of Dr. Kothapalli’s lab in developing and translating TRUSPA imaging systems for in vivo human prostate imaging, and the expertise of Dr. Wang’s lab in developing novel functional imaging biomarkers of PCa. The central hypothesis is that the TRUSPA is capable of mapping a list of functional and structural imaging biomarkers in the human prostate in a real-time non-invasive manner for detecting and differentiating clinically significant PCa. “In a current prostate cancer clinic, the standard procedure for diagnosis is ultrasound-guided needle biopsy,” Dr. Wang said. “Under the ultrasound imaging guidance, we insert small needles to the prostate to harvest some tissues and look at them under the microscope. We need to see if there is cancer in the prostate, and if there is, we need to determine the grade

of the cancer–if it’s aggressive cancer or non-aggressive cancer and how severe the condition is.”

Physicians rely on this diagnostic information to determine the next steps for treatment, such as the need to deliver chemotherapy or radiotherapy, or to perform surgery. All of these decisions depend on the diagnosis to determine the severity of the situation.

“The problem with current ultrasound imaging, which we rely on to determine where to insert the needle, is that it can be challenging to detect the cancer tumors in the prostate,” Dr. Wang added. “In current clinics, a more advanced form of imaging uses ultrasound and MRI fusion. Before having an ultrasound, the patient will receive an MRI to detect the tumors, and then during the ultrasound, the guided needle biopsy occurs, with the doctor looking at the insertion of the needles, and the MRI image is fused with ultrasound. There can still be misalignment issues, making the insertion challenging. We really need a highpowered imaging technology to guide the harvesting of tissues during the needle biopsy. In our research, we are working to build a multimodal imaging technology called photoacoustic imaging, which is laser-induced ultrasound imaging. This imaging technology can be combined with ultrasound so we can get two sets of images. The combined image can tell you a lot of information about the functional changes in the tumor. For example, cancer usually has newly formed blood vessels and sometimes has low oxygen saturation; the newly formed blood vessels are also usually leaking. The photoacoustic imaging presenting these functional changes is more sensitive to detect cancer than traditional ultrasound imaging presenting tissue structure changes, so it will significantly improve the accuracy in guiding the needle biopsy.”

The clinical study is simultaneously happening at the University of Michigan and Penn State, with each location testing 25 patients. “By researching our 50 subjects, we will test the performance of this imaging system, which will tell us whether this process can help us to detect aggressive prostate cancer,” Dr. Wang said. Dr. Wang’s team is working with the urologists, including John Wei, MD, and Simpa Salami, MD, at Michigan Medicine to recruit patients interested in participating in the study.

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SHIKANOV LAB RESEARCHES WAYS TO IMPROVE QUALITY OF REPRODUCTIVE HEALTH STORY BY MICHELE SANTILLAN

The research in the lab of Ariella Shikanov, Associate Chair for Undergraduate Education, Biomedical Engineering, Associate Professor, Biomedical Engineering, and Associate Professor, Obstetrics and Gynecology, aims to preserve and restore reproductive and endocrine function for at-risk populations, with a specific focus on engineering biomimetic environments for growth and maturation of ovarian follicles.

Ovarian follicles are multicellular aggregates in the ovary that are responsible for a woman’s fertility and ovarian endocrine function. Currently, young women and prepubertal girls diagnosed with cancer and facing ovotoxic treatments have limited options to preserve their fertility, resulting in premature depletion of the non-renewable ovarian reserve, the inability to have children, and significant alterations in endocrine function. Dr. Shikanov is in her 12th year at U-M BME and recently discussed her work.

“We are interested in creating artificial constructs that direct tissue regeneration and restore biological function by combining approaches from engineering, materials, chemistry and life sciences,” Dr. Shikanov said. “The clinical problem we want to solve is premature ovarian insufficiency (POI), which is a common outcome of anticancer treatments in young girls and women. POI causes sterility and complications related to absent ovarian endocrine function such as premature osteopenia, muscle wasting, impaired cognitive development, and accelerated cardiovascular disease. We aim to engineer a biomimetic environment that promotes in vitro growth of immature follicles and integrates cellular, molecular and physico-chemical properties with a structural design that allows studying the bi-directional interactions between the follicles and the support cells. Engineered ovarian tissue with controlled physical and biological properties provides a supportive environment for ovarian follicle survival and development, graft remodeling and longevity after transplantation. Our lab is also interested in molecular mechanisms involved in early stage development of

ovarian follicles, development of novel 3D culture systems and immunoisolating hydrogels for transplantation of donor ovarian tissue.”

“My lab pursues research in three different directions,” Dr. Shikanov said. “There is an in-vitro project where we aim to develop a dynamic biomimetic system to culture ovarian follicles, which are the functional unit of the ovary, with the main goal to restore fertility by obtaining a fertilizable egg.” Dr. Shikanov’s collaborator in this project is Brendon Baker, Associate Professor of Biomedical Engineering. “We functionalized degradable poly(ethylene glycol) hydrogels with extracellular matrix (ECM)-sequestering peptides aiming to recapitulate the native ECM composition for culture and maturation of ovarian follicular organoids, hypothesizing that ECM-sequestering peptides would facilitate deposition and retention of cellsecreted ECM molecules, thereby recreating cell-matrix interactions in otherwise bioinert PEG hydrogels” Dr. Shikanov said.

“When we encapsulate follicles or any kind of cell in a synthetic hydrogel, the environment around the cell or follicle is inert, with minimal interactions between the cells and the environment,” Dr. Shikanov added.

“The extracellular matrix-binding peptides that we utilized allow sequestration and retention of the extracellular matrix proteins secreted by the cells to be retained in the hydrogel. If we’re looking at an everyday analogy, it would be like almost furnishing your own room with a given budget.

Everyone might do that differently. Those peptides allow retention of the ECM of the extracellular matrix proteins secreted by the specific type of encapsulated cells, basically

allowing these cells to regenerate and restore their all-native environment. In this new paper, we have engineered a composite material which retains cell-secreted ECM for the culture of ovarian follicles by embedding electrospun dextran fibers designed by the Baker Lab and functionalized with basement membrane binder (BMB) peptide to drive the ECM to organize a line along those fibers truly mimicking the the fibrous structure of the native tissue. In the presence of ECM-sequestering fibers, encapsulated immature primordial follicles and ovarian stromal cells aggregated into large organoidlike structures with dense deposition of laminin, perlecan, and collagen I, leading to steroidogenesis and significantly greater rates of oocyte survival and growth. The conclusion is that the incorporation of this extracellular matrix of modified fibers is needed to allow reorganization and reclustering of the ovarian follicles. When you allow them to cluster and reorganize, you improve the survival of the oocytes, the non renewable germ cells. It is only when you have both the fibrous structure and the ECM sequestering peptides that these structures can reorganize themselves and actually continue growing and maturing.

“Basically, we combine this biomimetic system that has biological aspects, but because it’s a synthetic material, we can tune and control the mechanical properties of this system,” said Dr. Shikanov. “For this system, we isolated and encapsulated the most immature class of ovarian follicles and got them to grow to stages that have never been achieved before.

Dr. Shikanov said that young women

BME innovations

and postpubertal girls have the option of cryopreserving their eggs or embryos before undergoing sterilizing treatments.

However, there are many situations where these options are not available. For example, some patients have aggressive cancers that cannot wait for harvesting.

Also, if a patient has breast cancer, doctors cannot offer ovarian stimulation because of elevated estrogen levels which may affect the outcomes of the treatment. And lastly, young prepubertal girls needing anticancer treatments don’t have any options for fertility and endocrine ovarian function preservation, because their prepubertal ovaries cannot produce mature eggs in response to ovarian stimulation. As a result, childhood cancer survivors may suffer from premature ovarian insufficiency caused by anticancer treatments and experience significant negative implications on their endocrine health that compromise their normal physiological growth. As Dr. Shikanov explained, the ovary plays a role beyond fertility through its ability to affect metabolism, bone growth and density, cardiovascular and endocrine health.

“The second project of my lab aims to address the need to restore ovarian endocrine function in childhood cancer survivors and uses biomaterials with the goal to develop an immuno isolating capsule,” she added. “The immuno-isolating capsule allows us to encapsulate donor tissue, and implant it in the host without the need for immunosuppression. The implant can cross-talk with the rest of the body,respond to circulating hormones and secret sex hormones in a dynamic and physiological pattern.”

“This project was recently funded through the National Institutes of Health to start animal studies in non-human primates in collaboration with the Oregon on Human Primate Center,” said Dr. Shikanov. “This grant is huge because we will get as close to human subjects as possible.” Dr. Shikanov and her graduate students will implant immunoisolating capsules in six Rhesus monkeys and follow them for 18 months. To bring the research to fruition, Dr. Shikanov had to start a company. “We’ve completed all of the pre-technical studies and we are submitting an investigational new drug

application to the FDA so that once it gets approved, there is a protocol for a clinical trial,” she said. “Once it gets approved, we can start fundraising through venture capital and then eventually start a clinical trial, putting it in humans.”

“The third and the newest project in my lab that’s been alive only for maybe five or six years, is the gender affirming hormone therapy (GAHT) project, and for that project, specifically, we’re looking at the effect of cross-sex-hormone administration in gender-affirming hormone care,” Dr. Shikanov said. “Basically, we are looking at the effect of testosterone on females and vice versa, estrogen on males. We were the first ones to develop and report an adult and adolescent Testosterone GAHT mouse model to study this topic.”

Dr. Shikanov and her collaborators– Molly Moravek, a U-M clinician and Associate Professor in the Department of Obstetrics and Gynecology, and Vasantha Padmanabhan, Professor of Pediatrics– know that there are information gaps and uncertainty around the long-term consequences of how gender-affirming

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30 | BME innovations hormone therapies impact important aspects of health, such as reproduction.

“To address this, we developed the first animal model to study the effects of genderaffirming hormone therapies on fertility and general health of the offspring,” said Dr. Shikanov. Some of their findings were recently published in a paper in Advanced Biology.

The researchers examined the impacts of estradiol-containing hormone therapy in mice assigned male at birth who were undergoing E-GAHT. In these cases, E-GAHT usually involves lifelong administration of estradiol, the primary form of estrogen, along with a class of drugs called anti-androgens, which prevent androgens like testosterone from exerting their biological effects in the body. The research team found that existing human data concerning the testicular effects of estradiol-containing hormone therapies are primarily derived from observational studies conducted around the time of surgery.

These studies often involved short-term exposure, variable estradiol formulations

and differing rates of anti-androgen usage, resulting in inconsistent findings.

As noted in Advanced Science News, male mice were treated with estradiol hormone therapy at low, intermediate and high doses, with a result that testosterone and follicle-stimulating hormone levels in the blood were suppressed while estradiol levels were elevated to levels observed in female mice—mimicking what happens in human patients on a similar regimen.

All doses seemed to have some effect on the testes and bladder, but the most significant finding was that six weeks of estradiol therapy resulted in altered sperm motility, though it did not alter the presence of mature sperm. “Sperm with altered motility is less likely to fertilize an egg and may result in inability to conceive,” said Dr. Shikanov. “However, altered motility is only one aspect of impaired spermatogenesis (sperm maturation). We anticipate that longer [estradoil therapy] may eliminate mature sperm altogether.”

The research team thinks that this study in animal models will encourage additional

“

We developed the first animal model to study the effects of gender-affirming hormone therapies on fertility Ariella Shikanov, Ph.D. Associate Chair for Undergraduate Education, Biomedical Engineering Associate Professor, Biomedical Engineering

Ovarian cancer cells

clinical research, with the long-term goal of providing data needed to help clinicians appropriately counsel patients on the reproductive effects of estradiol hormone therapy. “Additional studies, such as the effect of estradiol hormone therapy on testes and genetic changes induced in the testes and in the sperm, are currently being pursued,” said Dr. Shikanov in the article. “More importantly, whether these effects are reversible after estradiol cessation and whether these effects become less reversible with time will be critical for the clinicians and the trans community to know.” The team is also eager to use their animal models to understand the effects of estradiol hormone therapy on reproduction following treatment with puberty blockers in adolescents, as well as investigate the effects on the health of offspring born from gametes exposed to estradiol. “Our current findings and future investigation in animal models or through clinical observation will shed further light on the effects on offspring’s general health and fertility,” added Dr. Shikanov.

BME innovations

U-M WEIL INSTITUTE, COLLEGE OF ENGINEERING & MICHIGAN MEDICINE AWARDED $5.7M GRANT FOR WEARABLE SENSOR THAT DETECTS DISEASES THROUGH BODY ODOR STORY BY JIM LYNCH Researchers from the University of Michigan’s Max Harry Weil Institute for Critical Care Research and Innovation, College of Engineering and Michigan Medicine have received a $5.7 million grant from the NIH Screening for Conditions by Electronic Nose Technology (SCENT) program to develop a portable sensor that uses body odor to detect over 20 acute and chronic, inflammatory, metabolic, respiratory, cardiovascular and skin diseases in both adults and children.

Xudong (Sherman) Fan, PhD, U-M Richard A. Auhll Professor of Biomedical Engineering and an Associate Director of the Weil Institute, is leading a collaborative team of engineers, data scientists and clinicians to build a device that integrates gas chromatography (GC) technology with electronic nose (e-nose) and vital signs sensors into a wearable system capable of analyzing the unique chemical signatures found in vapors emitted from the skin.

“It has been well known since Hippocrates that many diseases have distinct odors associated with them, such as the fruity smell that accompanies diabetic ketoacidosis,” said Dr. Fan. “These odors are the result of volatile organic and inorganic chemical compounds emanating from the skin, which are reflective of the human body’s metabolic processes as well as the bacteria and viruses living within it. Analyzing these compounds could

provide us with unique diagnostic clues, guide laboratory evaluation, and facilitate and expedite treatment.”

The device will also be able to detect and analyze physiological information such as heart rate, respiratory rate, blood oxygen level, and total water loss through skin.

Currently, few technologies exist for wearable body odor analysis. Benchtop GC devices are commonly used but are too bulky and impractical to be deployed at the pointof-care. E-nose sensors, while providing a simpler and faster alternative, are susceptible to environmental changes and can suffer from strong cross-talk among their various sensing elements when they are exposed to all of the vapors that are emitted from the skin simultaneously. By combining wearable GC and graphene-based e-nose technologies developed at the University of Michigan with advanced machine learning and artificial intelligence algorithms, the project team aims to surpass the limitations of current body odor analysis methods and greatly enhance their device’s pattern recognition and disease detection capabilities.

The team plans to tackle an array of clinical conditions in both adults and children ranging from critical illnesses like sepsis, stroke, congestive heart failure, GI bleeding, and diabetic ketoacidosis to skin diseases (such

as psoriasis) and pulmonary diseases (such as asthma and COPD). The noninvasive and wearable nature of the device could have significant impact especially in the acute care space, where rising admission rates are leading to overcrowding and, subsequently, worsening outcomes.

“Undifferentiated critical illness is challenging and requires rapid diagnostic workup and monitoring in order to tailor and titrate lifesaving therapies,” said Kyle Gunnerson, MD, Professor of Emergency Medicine, Anesthesiology, and Internal Medicine, as well as a Weil Institute member and the lead PI for the project’s Acute Care and Diseases focus area. Dr. Gunnerson is also the Emergency Critical Care Division Chief and oversees Michigan Medicine’s emergency department-based ICU, the Emergency Critical Care Center (EC3). “There is a direct relationship of increased mortality and the time a patient waits in the ED for an available ICU bed.

Noninvasive wearable monitoring devices such as this could provide timely information needed to help identify, manage, and monitor many instances of acute critical illness and injury earlier than what is currently available.”

“Because people will simply wear the small device, it can also be used in a variety of settings outside of the hospital, such as homes and workplaces,” said Fan.

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MEET OUR BME STUDENT ORGANIZATIONS Biomedical Engineering Society (BMES)

The primary goal of the U-M chapter of the Biomedical Engineering Society (BMES) is to serve undergraduate and graduate students interested in biomedical engineering by assisting their academic, professional, and social development. The organization strives to provide information regarding curriculum options, research opportunities, and industrial and academic employment prospects. It also distributes information about biomedical engineering to the University community and encourages unity among the BME department’s students, faculty, and staff, as well as interested individuals from other disciplines.

Members of the U-M BMES chapter attended the BMES Conference in Seattle in October. For the 2023-2024 Academic Year, the group has 357 total students on the interest list, with 202 of those declared BME students, and plans a total of 23 events for this academic year.

The Graduate Student Council (GSC) ensures that the interests of graduate students of the BME department are represented. GSC works alongside departmental leadership to improve the graduate student experience. GSC hosts DEI-related, academic, and social events intended to support the graduate student body and facilitate community building.

Additionally, GSC organizes the graduate student recruitment weekend, orientation, and annual department retreat. Last academic year, the GSC had 77 members, including 13 Social Committee members, 15 Academic Committee members, and 12 DEI Committee members.

Highlights in GSC’s social activities in the past year included mini-golfing with Robotics, BME-GSC/BIONIC ice skating, several football tailgates, a BME 5k, a Great BME Bakeoff competition, and a March Madness tournament challenge. GSC-sponsored DEI- and mental health-focused activities included candle making, de-stress events with yoga and meditation, trivia, and movie nights. GSC-sponsored academic events included writing hours, Qualifying Exam practice nights, and the first annual Midwest Speaker Series. Plans for the 2023-2024 academic year include a first-year mentorship program, apple-picking and pumpkin patch trips, an internship information panel, weekly bagel socials, and events co-sponsored with other U-M student organizations, including a PharmD/ ChemE/BME mixer. For the 2023-2024 academic year, GSC has already hosted writing hours and its annual picnic/overnight graduate student retreat, with many more events on the way.

M-HEAL (Michigan Health Engineered for All Lives)

• National Organization • The University of Michigan chapter • Michigan BMES Facebook • Twitter @BMESUM Biomedical Engineering Graduate Student Council (GSC)

Michigan Health Engineered for All Lives (M-HEAL) is a U-M student organization that fosters interdisciplinary work in global health, design, and entrepreneurship. The group engages students from various backgrounds in these efforts through guest lectures, interactive workshops, and volunteer opportunities. They support 12 student-led

BME innovations project teams that develop health-care solutions and travel abroad to work with international partners. M-HEAL strives to cultivate a well-informed, creative, and collaborative community prepared to make a positive impact for global health.

M-HEAL’s mission is to use education, needs assessment, design innovation, and social entrepreneurship to improve access to health care in underdeveloped communities. Members envision a world where every person has access to appropriate, affordable, and high-quality health care.

The group is adding a new “clinical immersion, observation, and needsfinding” program. A goal for the fall semester is to formulate a program with Michigan Medicine doctors to assist in students’ development of observation and needs-finding skills that are a critical part of front-end design.

M-HEAL has reinforced its commitment to DEI by rewriting its DEI strategy to focus on equitable recruitment and equitable partnerships. M-HEAL received the 2022 MLK Spirit Award in the Student Organization category, largely due to its comprehensive DEl strategy.

M-HEAL has held series-style events, including workshops and panels, and has collaborated with Engineering Student Government & SWE (Society of Women Engineers). Some additional group events will include MentorMatch, featuring an older member matched with a new member for support and mentorship. M-HEAL has a strong commitment to volunteering. This coming year’s plans include: • World Medical Relief volunteering • Expanding volunteering opportunities in Ann Arbor • 3rd annual Campus Challenge The group also hosts a number of social events, including study groups, Ice-cream socials, ice skating, trivia night, sports, wellness activities and more. M-HEAL reinforces its collaborative event partnerships with other student organizations through activities such as the Global Health Symposium and STEMclusivity.

• M­HEAL: U of M Health Engineered for All Lives MedLaunch

MedLaunch is a community of students at the University of Michigan passionate about healthcare and biomedical innovation. Students of different backgrounds from Engineering, LSA, STAMPS, the School of Music, and many more participate in a year-long Biodesign Challenge to develop assistive technology for local community partners with disabilities. MedLaunch’s motto is that they design WITH community partners instead of FOR community partners, which means that members

work side-by-side with community partners to create a customized product that directly addresses their needs. At MedLaunch, the team enables members to become leaders, creative thinkers, and problem solvers. Together, they are making the community a healthier and more equitable place.

As their projects are year-long, students can apply to MedLaunch in the beginning of fall semester. They have a wide variety of projects ranging from Computer Science-based (i.e. game and app development) to mechanical-based (i.e. wheelchair adaptive bowling ramp). Learn more about their previous projects on their website or at their Final Showcase in April where current teams will present the culmination of their work.

• MedLaunch Website • MedLaunch Facebook • MedLaunch Instagram Michigan Sling Health

Sling Health is a national, student-run incubator that brings together engineering, medical, business, and arts and sciences students to invent novel devices and software applications targeting unmet clinical needs. U-M’s Sling Health chapter is one of eight chapters nationwide striving to make medical entrepreneurship more attainable for students and physicians.

Undergraduate and graduate students can apply to join Sling Health in the fall semester. Once admitted, students form teams based on the clinical problems they would like to solve, leveraging Sling Health’s clinical problem database to identify real-world, unmet clinical needs. Their ninemonth experiential curriculum includes three design reviews that guide students through clinical assessment, prototype creation, and business development. Teams receive access to several resources, to include funding, lab and workshop space, prototyping tools and equipment, legal services, and mentorship from experts. Additionally, students have the opportunity to pitch in various competitions, including the annual University of Michigan Demo Day and National Demo Day. • National Organization • The University of Michigan Chapter • Contact Our Executive Board (msling.command.23-24@umich.edu)

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Michigan Synthetic Biology Team The Michigan Synthetic Biology Team (MSBT) is affiliated with both the College of LSA and the College of Engineering. The organization operates as a cross between a research lab and an engineering project team. Each year, participants develop and execute a project in the field of synthetic biology.

Members come from a variety of disciplines, including BME, MCDB, Biochemistry, Computer Science, and others to work towards an annual project that is presented at the iGEM competition each fall.

In the last 4 years out of 14 years of MSBT competing at iGEM, MSBT has won nine medals, including a recent gold medal.

MSBT’s mission is to prioritize the building of an excellent space for diverse, talented and dedicated team members. The current team consists of 27 people, with more than a third of the students affiliated with BME. The team greatly benefits from guidance from faculty in departments such as biomedical engineering and MCDB, as well as grad student advisors in BME and chemical biology. MSBT adds to the diversity of student organizations in terms of the types of training the group provides its students, focusing on the research aspect.

New members have the chance to learn foundational web-lab and dry-lab skills that can be developed throughout the execution of the project. For more advanced members, MSBT is a good opportunity for them to have a great deal of control over the direction of team research and the troubleshooting that occurs throughout the research process.

MSBT also has an active mentorship network within the organization, enabling younger members to have access to really strong mentorship opportunities. MSBT also hosts a variety of community-outreach and career-development events that also benefit members.

Beta Mu Epsilon

Beta Mu Epsilon’s mission is to foster community and personal development through academic endeavors, professional growth, and

philanthropic service. The student chapter was established in 2015 and is open to all majors. Dr. Rachael Schmedlen is the faculty advisor.

The chapter has six pillars: biomedical, scholarship, professional, philanthropy, social, and membership. The group has hosted an Innovation Day and offers help getting internships and research. They also host a mandatory service event for all members, as well as many other service events. Beta Mu members also enjoy community-building events such as going to cider mills, alumni networking, as well as professional office hours and internship and resume advice.

The organization is also planning a Research Symposium, with a goal of introducing members to all of the different labs that are available on campus. Additional plans call for workshops about graduate school, studying abroad, and course planning.

Some specific community-service projects include a blood drive, canned food drive, and blanket-making for a local homeless shelter.

LatinXinBME In 2022, Carlos Aguilar, associate professor, biomedical engineering, founded a LatinXinBME group.

“I founded this group because Hispanic graduate students are now our department’s largest underrepresented minority and I wanted to form a support structure for them,” Dr. Aguilar said. “I wanted to celebrate these students, let them know they have a mentor who looks and speaks like them, and that there are others who share our heritage. We had dinners to meet one another last year and sponsored travel awards for students to present their work at conferences. I was able to obtain funding for this group through the Howard Hughes Medical Institute (HHMI) and a fellowship that supports Jesus Castor Macias (our College of Engineering’s first HHMI Gilliam fellow).” HHMI’s Gilliam Program invests in graduate students from populations historically excluded and underrepresented in science so that they are prepared to become scientific leaders.

“Thank you again to Dr. Aguilar for the opportunity and for making the LatinXinBME group possible,” said Carlos Urrego, a PhD student in Professor David Kohn’s lab. “I can’t stress enough how much it has changed my perception of the program and increased my sense of belonging.”

Dr. Aguilar said the group is intended to encourage and support Hispanic graduate students. “This year, I hope to achieve a few additional goals, such as building a bank of successful essays for fellowships (It’s my goal to get more Hispanic students winning prestigious fellowships), have practice presentations for students to introduce their work to one another, and, of course, eat!”

BME innovations

MI CHIGA N N EU RO P R OST H E T IC S TE AM EN GI N EER S H OP E FOR CHI LDREN STORY BY MICHELE SANTILLAN

“Our team, Michigan Neuroprosthetics, builds customizable and affordable prosthetic arms for children,” said team leader and student Meha Goyal, the President of the group. “So far, we’ve been working with local patients, such as Julian and Michael, who range from about 12 to 16 years old. We’re also working with patients internationally in Syria by partnering with the Syrian American Medical Society to provide prosthetic arms to three children there.”

The team, which is assisted by Cindy Chestek, Associate Professor of Biomedical Engineering, as its faculty advisor, consists of seven subteams: assembly, software, electrical, manufacturing, mechanical, outreach and interfaces. Each subteam has about 15 to 20 people, with 30 to 40 percent of the entire group’s students consisting of BME majors.

“The assembly subteam is in charge of taking all of the team’s work and putting it together for the final product,” Goyal said. “Software is in charge of building the software, electrical builds our sensors and circuits. Manufacturing is the team that works on exploring the materials that they 3-D print, making sure that our 3-D prints are strong and durable. Mechanical is in charge of figuring out how the arm is going to open and close and the mechanics of how the arm will move. Outreach does a lot of great work connecting us to patients and making sure that the delivery process is smooth and generally building our team community and

relationships with our patients. Finally, we have interfaces, which is a team focused on making the arm as comfortable and usable for the user as possible and in charge of making it more lifelike and human. They’ve been doing some really cool things with making skin-type variance to make the arm look more human-like and they also work on making the connection between the prosthetic and the residual limb of the patient more comfortable.

It has been a pleasure to watch this team distribute prosthetic hands over the years,” Dr. Chestek said. “It’s amazing how much energy they have for constantly improving their designs.”

The group was established in 2015 by then student Aaron Chow. “He knew someone who was in need of a prosthetic, but the prosthetic that the family needed to buy was, unfortunately, incredibly expensive and they couldn’t afford to buy their child a new one” Goyal said. “As an alternative, the student and some of his friends got together to try to build an affordable prosthetic arm, keeping the cost under $200 to provide to the family. That’s where our organization started.”

To keep the prosthetics affordable, the team focuses on producing as much as they can instead of buying components from outside vendors. “For example, we’re working on designing our own electrical circuits,” Goyal said. “We 3-D print the base of the arm and we

work on ways to make the print stronger so that we can achieve a similar quality and strength (as company-produced limbs) with more affordable materials. We also develop our own software and open-source our arms so that anyone who wants to can use these designs to build an arm of their own just by following the guides, designs and software that we provide.”

Goyal said that most of the team’s money comes from grants and university funding, so they use that to try and provide as many affordable arms as possible. The team welcomes new members through an application process, with a focus on ensuring that applicants are committed to the team’s goal “because we’re really committed to our patients and we want to make sure that we can deliver our prosthetics to them on time and with high quality.” Goyal said. “We want people who have a similar dedication coming into the group.

It’s really exciting, because I feel like I’ve done a lot of software-engineering-type things, but it’s really nice to be able to really work directly with a patient and see them be able to use what you make and see what they can do with the technology. You get to use a wide variety of skills no matter where you come from in the university to make an impact on the patients who we work with, so I encourage anyone who has a genuine interest in the work we do to come out and apply because we’d love to have you.”

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B M E G R A D UAT E S FA LL 20 22- S UM M E R 2023

FALL 2022 Bachelor’s Program

Master’s Program

PhD Program

Ismael Zakaria Assi Claire Marie Casey Eason Chang Christian Yvette-Ware DeVaull Isabel Marie Dziuba Alec William Eames Zakhar Frolov Serena Gupta Don Hua Seowoo Julie Kang Rosie Kwon Marisa Anne Leo Timon Lwo Justin Terrell Mason Fu Yuen Ngai Rabiah Odumosu May Thazin Phoo Joseph Michael Reynolds Kennedy Marie Rogers Eamon James Salfi Yinghao Wang Katherine Treat Winslow Bokyung Woo

Anna E Argento (MS) Megan Cox (MS) Jillian Cwycyshyn (MSE) Adler Elliott-Rosenberger (MS) Tucker Michael Endersbe (MSE) Sai Sirish Gokavarapu (MS) Andrew M Golin (MSE) Jinrun Huang (MS) Neha Sara John (MS) Suraj Deepesh Kholwadwala (MSE) Junggon Lee (MSE) Sheng-Wen Lin (MS) Basheer Mossallam (MSE) Hengle Pan (MS) Ritika Parikh (MSE) Shivani Patel (MS) Andrew James Rice (MSE) Ishani Sharma (MS) Chih Hsuan Tsai (MS) Zoe Vandenberg (MSE) Pit Vollmers (MS) Lauren Ashley Wich (MSE) Zhiqing Yin (MS)

Kritika Iyer Michelle Karker Yue Qin Tiana Jasmine Wong

Natalie Chan Selina Chen Sue You Chong Kristina Chienyee Chu Jenna Marie Cicatello Mitchell Halsey Cook Alexa Ann Cotter Madison Daminato Vincent Isidore Elfrink Olivia Jane Farney Valeria Cristina Ferre Julia Lauren Finley Luke Wallden Fisher Connie Su Gao Benjamin Travis Gerber Camryn Amel Graham Rogina George Hanna Lauren Hesse Darcy Donghua Huang Qin Huang

Elizabeth Ruth Hughes Marcus Jackson Christopher Tuschen Jeffers Zoie Marie Jones Eddie Jung Claire Elaine Kalajian Shreya Kashyap Charlise J Keck Natalie Renee Koenig Krishna Sai Koka Keith Douglas Kozma Devon Grace Krasner Kaitlyn Renee Kunselman Aham Lee Alex Shuan Li Annie Li Kevin Lin Amanda Rose Liss Jenni Liu Richard Shuo Liu

WINTER 2023 Bachelor’s Program Grant Robert Acker Deborah Temilolu Akinbola Leanne Alawieh Amogh Angadi Connor Annulis Abhilash Balanethiram Elkin Diego Bayraktar Zeinab Hussein Bcharouche Mason Beaker Maya Sydney Behrend Brooke Julia Berens Jordan Savannah Blaine Amanda S Bluem David William Bosek Brennan William Callow Julianna Eileen Caton Matthew L Chang

BME innovations Elizabeth Grace Lombard Kaye Lundy Miranda Abigail Makowski Sho Matono Ebony Rose Matthews Ryan Carlyle McCloskey Trenton Earl McLean Audrey Angeles McManus Elizabeth Marie Mittag Jaimee L Moline Sommer Anne Motley Lauren Renee Mudry Daniel Danesh Najarian Simi Neeluru Ritika Pansare Gauri Gautam Patel Raj Kamleshbhai Patel Robyn Nicole Pfeiffer Kaitlyn Mary Pierpont Joel David Pingel Andrew Qian George A Rabadi Ridesh Rai Parth Raut Rithika Reddi Colin David Reinhart Kyle Matthew Riekki Zachary David Roberts Jan S Rosa Crystal Sanchez Justin Maxwell Schaaf Eve Hava Shikanov Eli Brett Siegel Elizabeth Peyton Snider Kathryn Jane Suarez David Brenton Svacha Ansen Qie Tan Lauren Elizabeth Terry Jorden Thompson

Tyler Jacob Tish Matthew Tong Andrew Richard Tuokkola Trevor James Underwood Samantha Vacca Tyler Ryan Vallier Faith Adel Van Allen Abigail Grace Wandoff Scott Joseph Westrick Jr David Kim Willett Kira Lorraine Woodhouse Eldon Yiteng Xu Henry Xiaochen Xu Wuyuqing Yang Yongsoo Yuk Rachel Wang Zhang

Master’s Program Ariana Noor Afrakhteh (MSE) Obada Albaghdadi (MS) Jack Andrews (MS) Amanda Ayriss (MS) Layla Berry (MS) Melissa Ann Beyrand (MSE) Noah Martinez Blase (MSE) Gabrielle Blevins (MS) Shao-Chi Chen (MS) Wes Cummings (MSE) Jake Andrew Demeulemeester (MS) Dina Dragoljic (MS) Elizabeth Marie Dulzo (MSE) Isabel Marie Dziuba (MSE) Hanin Elhagehassan (MSE) Brandon Hardy (MSE) Felicia Hinojosa (MSE) Yu-Chi Huang (MS) Sydney Alicia Jones (MSE)

Jordan Lauri Kamen (MSE) Naomi Claire Kantor (MSE) Shivangi Kewalramani (MS) Hanna Hayung Kim (MSE) Jacob Daniel King (MSE) Samantha Lewis (MSE) Po-Chun Lin (MS) Yvonne Lin (MSE) Timon Lwo (MSE) Dalia Sherif Marakby (MSE) Nikhil Srinivas Mukkamala (MSE) Ruchika Nalabotala (MS) Samuel Eunjun Oh (MSE) Jordan M Olszewski (MSE) Rebecca Sage Pereles (MSE) Ethan Poupard (MSE) Hasan Ali Sawan (MSE) Ryan S Schildcrout (MS) Anjali Shankar (MS) Benjamin William Skubi (MS) Nicholas Robert Stec (MSE) Laura Aileen Williams (MSE) Kade Ethan Wong (MSE)

PhD Program Sang Won Choi Gurcharan Kaur Jacqueline Larouche Christina Lee Charles Lu Emily Ashley Margolis Mariana Masteling Pereira Negin Nadvar Greyson Eric Stocker Christopher Tossas-Betancourt Benjamin Albert Yang

SUMMER 2023 Bachelor’s Program

Master’s Program

PhD Program

Caleb Night Hekman Lis Martinez-Bernal Jared Matthew Pavlick Jayanth Sannuti Tatikonda

Donia Ahmed Zainab Salman A Alramadhan Harkirat Singh Arora Christina Capobianco Madeline Kay Eiken Myoungju Kang Madison McKenzie Kelberman Atticus McCoy Firaol Sisay Midekssa Adrian Porras Laura Luis Ruiz Perez Nadine N Samaha (SUGS) Emily Thomas Yi Tian Irene Zhang

Cara Ann Abecunas Elizabeth Bottorff Carolina Haeeun Chung Ciara Davis Nicole Erin Friend Sara Elizabeth Hopper Kathleen Elizabeth Kish Ning Lu Linyu Ni Tanner Hamilton Robison Evan Russell Rogers Guanhua Wang

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FIVE BME TEAMS RECEIVE DIVERSITY, EQUITY AND INCLUSION GRANTS WRITTEN BY MICHELE SANTILLAN

CONGRATULATIONS TO FIVE BME TEAMS THAT RECEIVED DIVERSITY, EQUITY AND INCLUSION 2023-2024 FACULTY GRANTS FROM MICHIGAN ENGINEERING AND THE RACKHAM FACULTY ALLIES AND STUDENT ALLY DIVERSITY GRANT.

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BME GRADUATE APPLICATION ASSISTANCE PROGRAM (BME-GAAP) The BME Graduate Application Assistance Program (BME GAAP) is a student-run initiative at U-M that supports prospective applicants from non-traditional paths or historically disadvantaged backgrounds by pairing them with current graduate students who can help review application materials throughout the process of applying to a BME PhD program. The students may come from a variety of educational, economic, cultural, and/or geographic backgrounds that are non-traditional, historically disadvantaged, or underrepresented within STEM, thus contributing to a lack of support and/or guidance in their pursuit of higher education. The graduate students who serve as mentors are volunteers, and make no guarantee that students who participate as mentees will be accepted into the U-M BME Ph.D. program or any other academic program.The goal of BME GAAP is to increase representation in all BME graduate programs and to make the national and international BME community more diverse, inclusive, and representative. The lead faculty member for this program is Karin Jensen, Assistant Professor of Biomedical Engineering.

DEI BOOK CLUB A BME DEI Book Club is launching in fall 2023, with the primary goal of bringing together a group of people in the department who share a common interest in learning, discussing, and working to improve DEI efforts within BME. The book club will meet four times over the course of the year (~one/quarter): and feature three book club discussions and one invited speaker seminar. The first book will be “Whistling Vivaldi: How Stereotypes Affect Us and What We Can Do,” by Claude M. Steele. Michigan Engineering, together with BME, will provide complimentary copies of each book in the language of the reader’s choice, along with a lunch during book club discussions. The lead faculty members for this grant are Aaron Morris, Assistant Professor of Biomedical Engineering, and Alexandra Piotrowski-Daspit, Assistant Professor, Biomedical Engineering and Assistant Professor, Internal Medicine – Pulmonary and Critical Care Medicine Division.

FACULTY WELLNESS EVENT Professor Lisa Pruitt from the University of California Berkeley, recently published a memoir titled “Soul of a Professor: Memoir of an Un-engineered Life.” Her memoir addresses the critical and timely topic of well-being for faculty in academia. A faculty breakfast with Professor Pruitt to discuss the book sparked needed conversations about supporting faculty well-being and initiated timely conversations with Michigan Engineering faculty regarding the importance of self-care to support mental health. The BME lead faculty are Karin Jensen, Assistant Professor of Biomedical Engineering and Andrew Putnam, the Robert C. Leland, Jr. and Donna D. Leland Professor, Biomedical Engineering and Cardiovascular Medicine, along with Ann Jeffers, CEE Associate Professor.

BME innovations

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BME NEST: NETWORK FOR ENGINEERING SUCCESS AND TRANSFORMATION The BME Nest: Network for Engineering Success and Transformation is in its second year of providing resources for support to BME students. The goal of the program is to bring together first-generation and transfer students so they can encourage each other to succeed in their academic and professional goals. This student-centric group meets to provide information about topics such as financial aid, careers, department news and other items within a community of peers. Students serve as Ambassadors who connect with other students in the program so that no one feels alone as they start their college experience. The format is informal and is arranged to encourage camaraderie and student interaction. A main guiding element of the BME NEST program is that it proactively provides students with access to information and support that is designed to help them achieve. Rather than students needing to search for support, it will be provided organically in the NEST. NEST is focused to increase the diversity of the applicant pool, as well as to create a welcoming and supportive environment for students once they have entered the program. The lead faculty members on this program are Kerri Boivin (Director of the Engineering Career Resource Center), Karen Gates (BME Alumni, Development, and Industry Relations) and Jan Stegemann (BME Professor and BME MEng Program Director).

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BME-INCLUSIVE TEACHING The BME-IT initiative received the Rackham Faculty Allies and Student Ally Diversity Grant. The grant involves seven BME faculty, five BME students, CRLT and C-SED. It aims to engage graduate students and faculty to make improvements to BME courses over the summer and fall to improve equity, diversity and inclusion in our teaching. The goal is to deliberately cultivate a learning environment where all students are treated equitably, have equal access to learning and feel valued and supported in their learning through group interactions and course content. In feedback from the first year, IT-BME students responded that case studies and/or discussing the socio-technical aspects of engineering added value to the courses that incorporated these strategies.The lead faculty member on this program is David Nordsletten, Associate Professor, Department of Biomedical Engineering and Cardiac Surgery.

FACULTY WELLNESS EVENT Lisa Pruitt, Professor of Mechanical Engineering and Bioengineering at the University of California, Berkeley, led a conversation focusing on faculty wellness and mental health on Friday, November 3, as the featured speaker at BME’s DEI Book Event. Dr. Pruitt, the author of Soul of a Professor: Memoir of an Un-engineered Life, discussed her book and the lessons she learned from her challenges. College of Engineering Interim Dean Steve Ceccio opened the session.

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NEW STAFF GABRIELLE BLEVINS

SARA BURGESS

JULIE DE FILIPPO

DINA DRAGOLJIC

Research Lab Specialist Associate

Biomedical Engineering Building Manager

Research Administrator, Lead

Research Lab Specialist

Gabrielle Blevins joined BME in June 2023. Her previous position was as a BME Master’s Student/ Laboratory Assistant. Blevins has a BS in Bioengineering from the University of Toledo and an MS in Biomedical Engineering, University of Michigan. She also has a Certificate in Innovation and Entrepreneurship, University of Michigan.

Sara Burgess started her BME role in October 2023 and formerly was a Michigan Medicine Facilities Manager/Construction Project Manager with Facility Operations. She has degrees from Appalachian State University and Eastern Michigan University, Human Resource Management.

Burgess brings more than 20 years of experience at the University in a variety of roles including occupational safety, facilities, and human resources. In addition, she brings a wealth of knowledge in facilities/construction project management including at the U-M Health’s Cancer Center, Cardiovascular Center, Brehm Eye Center, and Taubman Health Center.

Julie De Filippo joined BME in August 2022. In her previous position, she was an RA for the Michigan Clinical Trials Support Group, supporting Anesthesiology, Allergy, Family Medicine, MEND, Pulmonary, Neurosurgery, Ob/Gyn, PM&R, Psychiatry, Radiology, and Urology as well as any department submitting an NIH or sponsored funding proposal that included a clinical trial component.

She has been with the University as a Research Administrator since 1996.

She completed both her undergraduate and graduate education at Nazareth University in Rochester, NY. Her undergraduate degree was English Literature with an Elementary Education minor.

Her Master’s focused on Special Education.

Dina Dragoljic is the Research Lab Specialist for the Putnam Lab. She manages the daily operations for the lab, such as procurement and safety needs, while also conducting her own research in the field of vascular tissue engineering.

She previously worked for Terumo Cardiovascular as a Test Engineer on their CDI Blood Parameter Monitoring system. Dragolijic received her Bachelor’s of Science in Biomedical Engineering, minoring in Nanoscience and Nanotechnology, at Florida Institute of Technology in 2021 and then came to U-M, where she received her Master’s of Science in Biomedical Engineering, concentrating in Biotechnology and Systems Biology, in 2023.

BME innovations

AMBER HALEY

Research Lab Specialist Associate Amber Haley joined Jiahe Li’s lab conducting experiments and analyzing data related to genetic engineering microorganisms such as E.coli. She graduated from Eastern Michigan University (EMU) in April 2023 with a Bachelor’s of Science in Biology with a Cellular and Molecular Biology focus, and has a minor in Sustainability.

At EMU, Amber was an undergraduate researcher studying the dynamics of harmful algal blooms and was a laboratory assistant where she helped prepare reagents for class labs.

TONY MARTIN

MICHAEL MEISTER

JEANNE SANDERS

Facilities Assistant

Chief Department Administrator

Research Lab Specialist

Michael Meister joined BME in May 2023 as Chief Department Administrator.

Before coming to BME, Meister was an ITS Program Manager and Climate and Space Sciences and Engineering Department Administrator. Prior to coming to U-M in 2013, he had 18 years of experience at Western Michigan University as the Director of University Budgets and Financial Planning. Meister has a bachelor’s degree and a Master’s in Public Administration, both from Western Michigan University.

Jeanne Sanders joined BME in September 2022 as a staff researcher. Her previous position was as a Postdoctoral Researcher.

Sanders earned her BS and PhD in Electrical Engineering from NC State. Her graduate research focus was in micromachined biomedical ultrasonic transducers, and her post-graduation focus was in engineering-education centering equity.

Tony Martin joined BME in November 2022 as Facilities Assistant, handling building and maintenance issues. Prior to his role in BME, Martin was in Facilities in U-M’s School of Nursing. He attended Eastern Michigan University, earning his undergraduate degree in Criminal Justice.

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NEW STAFF MICHELE SANTILLAN

ANJALI SHANKAR

REBEKAH SMITH

Communications Manager

Research Lab Specialist Associate

Michele Santillan manages print and digital media, and marketing and communications for BME. Before starting in the department, she was the Marketing Communications Specialist for U-M Civil & Environmental Engineering.

Santillan has a bachelor’s degree in journalism and public relations, and a Master’s degree in corporate communications, both from Wayne State University.

Anjali Shankar joined BME in August 2023. She previously was a Master’s student at U-M. Shankar has an MS in Biomedical Engineering with a concentration in Bioelectric & Neural Engineering from U-M in 2023, and a BSE in Biomedical Engineering with a concentration in Devices & Instrumentation (Minor in Electrical Engineering) from Case Western Reserve University, which she received in 2021.

BME Chief of Staff & Strategy and CoE RPM Director of Financial Operations Rebekah Smith served as BME interim unit administrator from September 2022 until May 2023; she joined as BME Chief of Staff & Strategy in April 2023.

Smith has worked for 18 years in Michigan Engineering, with 11 years in Computer Science Engineering in various roles, 3 years as Industrial Operations Engineering unit administrator and continues to serve in RPM as Director of Financial Operations for over 4 years. Smith has a Bachelor’s degree in Business Education from Pensacola Christian College, and a Master’s degree in Executive Leadership from Liberty University.

BME innovations

ALLIE THARP

ALI VON AU DOUGLAS

LUOLUO XU

RUI ZHANG

Academic Advisor

Project Manager Senior

Research Administrator Intermediate

Research Lab Specialist Associate

Luoluo Xu works in BME operations staff and previously was a Financial Specialist in U-M’s Taubman College of Architecture and Urban Planning. She has a Master’s degree in accounting from Eastern Michigan University.

Rui Zhang joined BME as a lab manager. Zhang graduated from the Institute of Zoology, Chinese Academy of Science, with a Master’s degree in biomedical engineering in 2017.

Allie Tharp started at BME in October 2022 and handles undergraduate academic advising and student support and services. Previously, she worked in Undergraduate and Graduate Recruiting and Admissions at the Ross School of Business and as Academic Success Advisor in the Athletic Department.

She earned ​a B.A. in Communication Studies from U-M in 2016 and an M.A. in Education - Leadership & Counseling (School Counseling) in 2021.

Ali Von Au Douglas’ role in BME is to collaborate with departmental and college stakeholders to manage and implement complex projects and initiatives for the department. Prior to starting in BME, she was a Project Manager in the U-M Medical School’s Office of the EVPMA/Dean where she worked on executive leadership recruitment and other projects related to the academic mission. Von Au Douglas graduated from Grand Valley State University in 2013 with her Bachelor’s of Science in Allied Health Sciences, with a minor in Biology.

Congratulations to the following BME staff members who received promotions: Kristi Haynes, Mackenzie Moore, Allison Morris, Rachel Patterson, Jennifer Rieger & Claire Truskowski

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FACULTY AWA R DS Susan Brooks Herzog Endowment for the Basic Sciences (EBS) Research Accelerator Award Sriram Chandrasekaran 2023 Endowment for the Basic Sciences (EBS) Teaching Award Winner for the Biomedical Engineering Department 2022 EBS Accelerator Award 2023 Chad Carr Pediatric Brain Tumor Center P3RC award 2023 Research Scouts Award for Bold Ideas, Michigan Medicine Cindy Chestek Miller Faculty Scholar American Institute for Medical and Biological Engineering (AIMBE) Fellow Dennis Claflin (Retired) BME’s Departmental Faculty Award Rhima Coleman American Institute for Medical and Biological Engineering (AIMBE) Fellow Xudong “Sherman” Fan Richard A. Auhll Professor of Engineering Histotripsy Team (Zhen Xu, Timothy Hall, Jonathan Sukovich J. Brian Fowlkes William Woodruff Roberts) 2023 Distinguished University Innovator Award.

David Kohn BMES Fellow Scott Lempka 2​​ 022 Endowment for the Basic Sciences (EBS) Accelerator Award Jiahe Li National Science Foundation CAREER Award National Institutes of Health (NIH) Director’s New Innovator Award Aaron Morris Defense Advanced Research Projects Agency (DARPA) Young Faculty Award Douglas Noll Institute of Electrical and Electronics Engineers (IEEE) Fellow

Alexandra Piotrowski-Daspit Emily’s Entourage Research Grant Rachael Schmedlen American Institute for Medical and Biological Engineering (AIMBE) Fellow Lonnie Shea 2023 Michigan Institute for Clinical & Health Research (MICHR) Distinguished Clinical and Translational Research Mentor Award Ariella Shikanov American Institute for Medical and Biological Engineering (AIMBE) Fellow Xueding Wang Jonathan Rubin Collegiate Professor of Biomedical Engineering Melissa Wrobel Associate Dean for Undergraduate Education Instructor Award

FAC U LT Y P R O MOT I O N S Deepak Nagrath, Professor, Biomedical Engineering Carlos Aguilar, Associate Professor, Biomedical Engineering Scott Lempka, Associate Professor, Biomedical Engineering and Associate Professor, Anesthesiology Sriram Chandrasekaran, Associate Professor, Biomedical Engineering

BME innovations

STU D E NT AWA R DS Anna Argento 2023 Rackham Predoctoral Fellowship

Merjem Mededovic 2023 Rackham Predoctoral Fellowship

Elizabeth Bottorff 2023 Susan Lipschutz Award

Firaol Midekssa 2023 Glenn V. Edmonson Scholarship for Graduate Biomedical Engineering

Margaret Brunette 2023 Rackham Predoctoral Fellowship

Kaitlyn Pierpont 2023 National Science Foundation Graduate Research Fellowship Program (NSF GRFP)

Carolina Chung 2022-2023 J. Robert Beyster Computational Innovation Graduate Fellowship Madeline Eiken 2023 National Science Foundation Graduate Research Fellowship Program (NSF GRFP)

Nicole Racca 2023 Derek Tat Memorial Award Brian Ross 2023 Glenn V. Edmonson Scholarship for Graduate Biomedical Engineering

Easton Farrell 2023 Rackham Predoctoral Fellowship

Crystal Sanchez 2023 National Science Foundation Graduate Research Fellowship Program (NSF GRFP)

Robert Graham 2022 ProQuest Distinguished Dissertation Award

Aman Tahir Marian Sarah Parker Prize - Undergraduate

Sara Hopper Social Change Award

Emily Thomas 2022 Derek Tat Memorial Award

Darcy Huang 2023 National Science Foundation Graduate Research Fellowship Program (NSF GRFP)

Javiera Jilberto Vallejos 1st Place Computational Biological Systems Student Poster Competition 17th U.S. National Conference of Computational Mechanics

Jordan Kamen 2023 Glenn V. Edmonson Scholarship for Graduate Biomedical Engineering

Emily Wallace Distinguished Academic Achievement-Biomedical Engineering Henry Ford II Prize

Gurcharan Kaur Richard F. and Eleanor A. Towner Prize For Distinguished Academic Achievement Prize Maggie Jewett Harold and Vivian Shapiro/John Malik/Jean Forrest Award Sheng-Wen Lin 2022-2023 Rackham International Student Fellowship Lauren Madden 2023-2024 J. Robert Beyster Computational Innovation Graduate Fellowship

Fulei Wuchu 2023 Glenn V. Edmonson Scholarship for Graduate Biomedical Engineering — Student Innovator Team Enginuity–Honorable Mention, National Institutes of Health National Institute of Biomedical Imaging and Bioengineering Design by Biomedical Undergraduate Teams (DEBUT) Challenge • • •

Team Captain: Jayanth Tatikonda Team Members: Connie Gao, Benjamin Gerber, Ritika Pansare, Joel Pingel and Jayanth Tatikonda Faculty Sponsors: Dr. Rachael Schmedlen, Dr. John Gosbee and Dr. Stephanie Sheffield

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STA FF AWA R DS College of Engineering Honors CoE Staff Incentive Program Awardees Tonya Brown Tara McQueen Allison Morris Bradley Wise

CoE Judith A. Pitney Staff Service Career Award Rebekah Smith

CoE Kenneth M. Reese Outstanding Research Scientist Award Dr. Jon-Fredrik Nielsen

Medical School Honors Endowment for the Basic Sciences (EBS) 2023 Research Staff Award Mackenzie Moore

BME Department Honors 2023 BME Outstanding Core Staff Awards Individual Awards: Peter Kartje Jennifer Rieger

Team Awards: Julie De Filippo Lara Kramer-Smith Luoluo Xu Kristi Haynes Allison Morris

A H EARTF E LT T H A N K YO U TO ALL OF OUR FACU LTY, STA FF AN D STUDEN TS FO R A L L YO U D O I N T HE BME CO MMU NITY

BME innovations

BME’s External Advisory Board (EAB) provides broad perspectives

STORY BY MICHELE SANTILLAN

The U-M Biomedical Engineering Department’s External Advisory Board (BME EAB) is a distinguished group of alumni and friends of the department who are committed to BME’s goal of solving important challenges in medicine and the life sciences to the benefit of humanity.

The BME EAB provides advice and support on key departmental priorities including: the student experience, research excellence, clinical translation, diversity, alumni and industry engagement and meets bi-annually to discuss strategic priorities and opportunities for BME at Michigan.

Samuel Achilefu, Ph.D.

Scott Merz, Ph.D.*

Professor and Lyda Hill Distinguished University Chair in Biomedical Engineering University of Texas Southwestern Medical Center

President and CEO MC3 Cardiopulmonary

Victoria Augustine, M.S.E.*

Aftin Ross, Ph.D.* Deputy Division Director Division of All Hazards Response, Science and Strategic Partnerships (DARSS), Office of Strategic Partnerships & Technology Innovation (OST), Center for Devices and Radiological Health U.S. Food and Drug Administration

Robert DeRyke, M.B.A.

Jason Weidman, M.B.A.*

Acting Director, Office of Patent Automation (OPA), United States Patent and Trademark Office (USPTO); Supervisory Patent Examiner, USPTO

President and CEO, Terumo Cardiovascular Group Executive Officer, Terumo Corporation

Caroline Dugopolski, M.S.*

SVP and President Coronary & Renal Denervation Medtronic

Erin West Farrell, Ph.D.*

VP of Program Management, Quality and Technical Operations, Cellino

Director, Toxins Strategic Projects AbbVie

David Knapp, Ph.D.*

Desmond Yeo, Ph.D. *

Vice President R&D, Vascular Boston Scientific President, Boston Scientific Foundation

*U-M Alum

Technology Manager MRI & Superconducting Magnets Technology & Innovation Center (R&D) GE Healthcare

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DARYL KIPKE, PHD

SCOTT MERZ, PHD

AURESA THOMAS MCGILL, PHD

THR EE ALUMNI RE C E I V E H O N O RS F RO M MICHIGAN E N GI N E E RI N G & BM E Congratulations to BME alumni Daryl Kipke, PhD; Scott Merz, PhD; and Auresa Thomas McGill, PhD, who received Michigan Engineering and BME alumni awards on Friday, September 22. Dr. Kipke received the Michigan Engineering Alumni Medal--the highest honor presented to an alum in the College of Engineering. Dr. Merz was honored with the Michigan Engineering Distinguished Alumni Service Award, and Dr. McGill received the BME Department Merit Award.

DA RY L R. K I P KE , PH D Daryl R. Kipke, PhD, is CEO and Managing Director of NeuroNexus Technologies Inc. and NEL Group Inc. Dr. Kipke has more than 30 years of experience working at the frontiers of biomedical engineering and neuroscience. As a professor of Biomedical Engineering at U-M, he served as Director of the Center for Neural Communication Technology and led the Neural Engineering Laboratory. As an entrepreneur, he founded several neurotechnology startup companies, including two spin-out companies from the Michigan College of Engineering.

Dr. Kipke’s work focuses on advanced neural interface systems and analytics for neuromodulation, bioelectric medicine, and electrophysiology. His research, which centers on developing miniaturized devices and systems that communicate with neural circuits throughout the brain and nervous system, has resulted in more than 200 scientific publications and dozens of patents. He advised more than 25 doctoral students and post-doctoral fellows, many of whom are now leaders in academia, government and industry. Dr. Kipke started his academic and research career at Arizona State University in 1992. In 2001, he returned to Michigan and served in the College of Engineering faculty until

he left academia in 2014. In 2002, Dr. Kipke founded Neural Intervention Technologies, Inc. and led it to success. In 2004, Dr. Kipke founded NeuroNexus Technologies, Inc. and has been instrumental in the company’s growth, overseeing its progression from university spinout to the subsidiary of a large public med-tech company. In 2019, he formed the NEL Group to re-acquire NeuroNexus and transition it back to an independent entrepreneurial company. He is currently CEO and Managing Director of the NEL Group and NeuroNexus.

Dr. Kipke is a Michigan Engineer many times over. He received his bachelor’s degree in engineering science in 1985. He then went on to earn a doctorate in Bioengineering in 1991, with master’s degrees in Bioengineering (1986) and Electrical Engineering (1987) along the way.

This Michigan journey is continuing with his family, with a total of 13 Michigan degrees—and counting—earned to date.

S COT T MERZ, P HD Scott Merz, PhD, is President and CEO of MC3, Inc., and serves on its board of directors. Dr. Merz is experienced in medical technology R&D, manufacturing and startup business formation.

His main research areas include cardiovascular devices, particularly for extracorporeal blood processing and cardiology, including expertise in biomaterials and blood-contact evaluation.

Specific examples of devices he has worked on include blood pumps, oxygenators, dialysis membranes, blood sensors, non-thrombogenic surfaces, coronary stents, heart valves, vascular grafts, ventricular assist devices, ultrasonic flow measurement, mechanical ventilators and catheters. Dr. Merz also has experience in commercial device development, regulatory trials and submissions, venture capital financing and commercial technology licensing.

Dr. Merz graduated from Duke University with a Bachelor of Science in Biomedical and Electrical Engineering in 1987. He received his Master’s of Science in Bioengineering in 1989, with areas of concentration in bioinstrumentation and control systems from U-M. He completed his doctoral degree at U-M in 1993, specializing in digital and analog automatic control.

Dr. Merz is a member of the American Society of Artificial Internal Organs, IEEE, and is a founding member and Advisory Board member of the Extracorporeal Life Support Organization (ELSO).

AU RESA THOMAS MCGILL, PHD Auresa Thomas McGill, PhD, RAC, is a Senior Manager in Regulatory Affairs for Abbott Diabetes Care. In this role, she supports the regulatory assessment of design and manufacturing changes impacting glucose monitoring devices to ensure the continued delivery of safe and effective products to the public. She also manages a team of regulatory professionals across multiple geographical locations. After joining the Abbott Diabetes Care team in 2022, Dr. Thomas McGill was recognized with the Regulatory Affairs Rising Star Award. She has previously worked as a Principal Design Quality Engineer and Regulatory Project Manager at Abbott within the Diagnostics Division and in Regulatory Affairs at Zimmer Biomet.

Her responsibilities have also included developing regulatory strategies for new in vitro medical devices and orthopedic devices, which launched in the US and internationally.

Dr. Thomas McGill received her doctorate from U-M, where she studied dynamic contrastenhanced CT imaging and tissue engineering.

U-M BME ALUM CREDITS FAMILY, EDUCATION AS INSPIRATION FOR DECISION TO ATTEND MEDICAL SCHOOL

BME innovations

DEVAK NANUA

STORY BY MICHELE SANTILLAN Devak Nanua (BSE, MSE) entered the world at Michigan Medicine and credits the life-saving leukemia treatment his mother received there while pregnant with him as part of the foundation for his desire to pursue Medical School.

Nanua, whose parents emigrated from India, described the excitement with which his father and mother arrived in Ann Arbor and their joy in planning to start a family. However, they would encounter serious challenges in fulfilling their dreams along the way.

“My mom was, unfortunately, diagnosed with leukemia in her late 20s,” Nanua said. “For a 27-year-old to be given that moment of facing her own mortality, it had to be so hard for her, especially having just come to this country.”

During his time as a student at U-M, Nanua was able to learn about his mother’s medical journey through the research notes and firsthand accounts of physicians and medical personnel who had provided her care two decades ago.

“She was given two options,” Nanua noted.

“If she did start the traditional drug treatment at that time, it would have meant aborting me.

It was a challenging decision. My parents had said that the best news they received that week was that they were expecting a child. My mom knew that her fertility would be limited down the road once starting treatment. Having newly immigrated, it was especially daunting to be facing this and having to make such decisions.

At Michigan Medicine, she had a great team of physicians and oncologists. I read the story of my parents and how I came into the world.

Everyone here worked with her and supported her. The only curative modality was for my

mother to have a bone marrow transplant from my younger aunt, who was only a teen at the time living in India.”

Nanua’s mother successfully had the bone marrow transplant and eventually recovered. “She was able to have me without complications,” Nanua said. “My mom got a second lease on life.”

Nanua added that as a child, he did not initially know or understand the magnitude of the health issues his mother had faced. “Throughout my years of growing up, there was a feeling of gratitude and a feeling of thankfulness toward the medical system that I picked up on from my mom,” he said. “I knew the relationship my mom had with her caregivers and the trust she placed in them. Even as a young kid, I was inclined to think about medicine in general terms as a possible career.”

When Nanua entered college, he ended up studying BME for his undergraduate and master’s degrees. “One thing that stuck out to me during my time in BME was my experience in our undergrad senior design project,” he said.

“It was this great opportunity to work with a diverse team of clinicians and engineers to solve a problem at the hospital. I realized I ultimately wanted to work in a space where patients can have the opportunity to experience an easier journey to health, despite their terrible ordeal.”

Nanua enjoyed the challenges that BME offered. “I had fun being an innovator on the engineering side, but it was only through meetings with clinicians, where they were able to point out important design considerations, that I saw issues from their perspective,” he said. “I felt like I needed a clinical experience background

to become a more efficient engineer in order to innovate in the space that I wanted.”

Nanua said U-M’s BME program offers students a rich curriculum. “I really appreciated the variety of courses that I got to take as a BME student,” he said. “By the time students are in their senior year here, they have studied aspects of the human body through the perspectives of mechanical engineering, materials engineering, electrical engineering, chemical engineering and computer engineering. By learning about the human body through the lens of different disciplines, it gives you enough tools to be creative and participate in many research projects or biomedical device design projects.”

As part of Nanua’s desire to make an impact through his work, he recently returned from a medical service trip to Rwanda. “As a medical student, I am a part of the Global Health and Disparities path of excellence,” he said. “Through this elective, I am able to learn about and discuss topics of health inequities and disparities in a global and domestic setting along with my peers and faculty who work in these spaces. At the end of our first year of medical school, we have a sixweek break where students can take some time to do whatever they want. I was always curious about the challenges of practicing medicine in an international and low-resource setting.

While being a part of this path of excellence, I had the pleasure to meet Dr. David Bradley, who is a Pediatric Cardiologist at Michigan who had been recently working in Rwanda. While meeting him, I was incredibly inspired by the work that he was doing, and this encouraged me to travel to Rwanda during my break.”

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STORY BY MICHELE SANTILLAN

​​ ME ALUM BLENDS HER PERSONAL, PROFESSIONAL B PASSIONS TO ADVOCATE FOR EQUITY AND ACCESSIBILITY IN HEALTHCARE AND MEDICAL DEVICES Nicole Bettè (BME BSE, 2016) is a Senior Human Factors Engineer whose personal experiences have informed and inspired her professional goals. In addition to her position with Kaleidoscope Innovation and Product Design, where she works as part of a team based at Eli Lilly in Indianapolis, Indiana, Bettè is Ms. Wheelchair New Hampshire USA 2023 and former Gilman Alumni Ambassador 2022-2023.

“I decided to join the Ms. Wheelchair USA program and apply for the Ms. Wheelchair New Hampshire USA title in order to have greater visibility for my platform, which is accessibility of healthcare and medical devices,” Bettè said. “As a Senior Human Factors Engineer, I’m in a great position to advocate for the accessibility of medical devices, both within the organizations where I work and also as a speaker at technical Human Factors Engineering conferences.

I also reach out to disability advocacy organizations and ask for relevant stories directly from the voices of disabled people so that I can better advocate. Although my focus is on disability, I consider other aspects of accessibility as well, such as access barriers or inequity due to race/ethnicity, gender/sex, anthropometrics, etc.”

Bettè knew she wanted to dedicate her life to healthcare and medical devices.

“I loved how much BMEs get to learn about different disciplines since it’s such a multidisciplinary field,” Bettè said. “Due to my educational background, I’ve been able to have in-depth technical conversations with mechanical engineers, electrical engineers, chemical engineers, material science engineers, industrial engineers, a variety of scientists, and a variety of medical professionals. Not many people can say that!

I’ve always been naturally curious about a wide variety of subjects even while my heart was rooted in healthcare, so BME felt like a very natural degree to pursue as it kept my brain engaged in all sorts of ways.” Bettè also loves engineering and discovered that BME was the perfect way to fuse her interests.

“When deciding between a biology-focused science and biomedical engineering, biomedical engineering felt more natural to me as it’s more application-based,” she added. “I’ve always been a very creative thinker and fixer. I needed the engineering

skills in order to channel all of that creativity and drive and turn it into practical solutions and real-world applications.”

Bettè’s journey to her degree and career encountered serious challenges along the way–challenges that would focus her career path to help others. “I struggled with illness and disability throughout college and spent what sometimes felt like half the time at medical appointments and emergency rooms,” she said. “I only had time and energy for academics, one or two extracurricular activities, and that’s it. I had practically no social life because any time outside of academics was spent looking for answers, or I was too ill to do anything. I didn’t know what was wrong. I was getting worse and was so afraid that I was dying that I signed up for a life insurance policy just before I began the arduous journey of seeking a diagnosis so that if I died young, my lowincome parents wouldn’t have to shoulder the burden of the six-figure debt I had gotten myself into. Furthermore, toward the end of my academic career, I was working two jobs at almost minimum wage and had to rely on food stamps and food pantries to survive.”

Through grit and determination, Bettè graduated with honors. “That picture of me in my graduation gown that a U-M photographer took captured the pure joy and pride I felt at that moment,” she said. “When I entered that stadium for my graduation ceremony, I had earned it. I had defied all the odds that told me that I wouldn’t graduate because I was poor, Latina, neurodivergent, disabled, chronically ill, a child of a divorced mother who had dropped out of college, and raised by a Cuban grandmother who only had a middle school education and who unfortunately knows what it’s like to have to share bubble gum with her four siblings and to have to survive on the broth from the same bone multiple meals in a row. All in all,

it took me three years longer than my peers to graduate, partially due to health reasons and partially due to internships, a few extra classes, and a semester studying abroad.”

Bettè’s health issues have stabilized and are now manageable. “I’m happy to report that I finally have a diagnosis (hypermobile Ehlers-Danlos Syndrome, a genetic connective tissue disorder), and no, I’m likely not going to die young,” she said. “I love my life and I love my job, and I have the help that I need. I’m disabled and proud of it, as my disability is a part of me and it has shaped the way I view life, has opened my heart and my mind to different perspectives, and has given me the experience, knowledge, and empathy to do what I do at work and do it well.”

Bettè encourages students who are facing challenges to reach out to the U-M community and to access available resources. “If you’re struggling with disability, don’t be afraid or ashamed to self-advocate, ask for help, and take advantage of every resource and accommodation U-M has to offer, just as I did,” she said. “U-M did an amazing job at retaining me. They have an impressive amount of structure and resources in place to help disabled and chronically ill students succeed. The staff and I were all very resourceful so that I could make it to that stadium and graduate. So, if you can, graduate. Disability in this country impoverishes most of us. It’s only because of my level of preparation and education that I’m not in poverty right now. I recognize that education in the U.S. is in great part a privilege, but if you happen to have made it this far as a student here and you’re vacillating between finishing and dropping out, finish, even if it means taking longer. I recommend working very closely with your professors and university staff, managing your schedule to give yourself time to rest

BME innovations

and go to medical appointments, reducing your course load, mixing and matching hard courses with easier ones when possible, surrounding yourself with a strong positive support system of classmates, mentors, friends, and family who can help you, and, if necessary, taking a break (medical leave/ sabbatical). There are also grants and scholarships available to help retain students who are in tough financial situations.”

Bettè believes that the need for diverse representation is great and that bringing people who will advocate for equity and inclusion will improve accessibility for others in the future. “On that note, there are few disabled healthcare professionals and few disabled medical device engineers like me,” she said. “I wish to see more of us so that our voices are represented and heard in this industry. I sincerely believe the lack of representation contributes to the access barriers we face in our healthcare system today (which includes inaccessible medical devices/equipment).”

Bettè explained that as a human factors engineer, she considers user safety, effectiveness, and ease of use as well as interface design accessibility, facility accessibility, and the inclusion of a wide variety of participants in usability studies,

including disabled participants. In terms of design, she thinks about multiple aspects of accessibility including, but not limited to, these five things: ·Enabling the design to provide information in multiple ways (not just visual or auditory information) and receive information in multiple ways (not just typing or just speaking). ·Simplifying the design and the instructions as much as possible to reduce the cognitive burden and complexity required to use it. This helps users’ ability to remain independent when using the device, reduces or sometimes eliminates the need for training, and reduces the likelihood that a use error will happen. ·Optimizing the ergonomics of both physical and digital interfaces so that users are able to comfortably use the device (with one hand, for example). ·Ensuring that the system or design works just as effectively and accurately for everyone who will use it. For example, sometimes optical devices don’t work as well for people with dark skin as they do for light skin, and with optical medical devices such as pulse oximeters and forehead thermometers, this can have adverse clinical impacts on people, hence its importance in

health equity. Similarly, some devices don’t work as well on larger people compared to thinner people. ·Leveraging universal and inclusive design principles across the entire development process.

Bettè is committed to reaching out to others so that their voices can also be heard.

“If you want to share your story pertaining to access barriers in healthcare, please feel free to reach out to me at bettenicole@gmail. com,” she said. “Stories are the single most powerful tool we have for advocacy! Please share yours with me!”

To help advocate for healthcare equity and inclusion, especially medical device accessibility, use the #AccessibleMedTech hashtag that Bettè created on social media.

If anyone is interested in learning more about or applying to the Ms. Wheelchair USA disability pageant, visit https://www. mswheelchairusa.org/. Ms. Wheelchair USA is run by The Dane Foundation, a 501(c)(3) nonprofit organization with a mission of improving the quality of life of people with physical and developmental disabilities. To learn more about The Dane Foundation, visit http://www.thedanefoundation.org/.

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THE I-CORPS MISSION: BRINGING RESEARCH INTO REALITY

STORY BY MICHELE SANTILLAN

Dr. Jonathan Fay, U-M BME Associate Professor of Practice and the director of U-M’s I-Corps program, has led the Midwest Region’s I-Corps program for the past 11 years, and joined U-M BME within the past year. He talked with BME Innovations to provide an overview of the I-Corps program and the role it plays in the BME community.

I-Corps was started by the National Science Foundation (NSF) in 2012, with the University of Michigan and Georgia Tech as the first two I-Corps nodes in the country. The nodes were charged with bringing innovation and entrepreneurship education to the PhD, postdoc and faculty populations of not only their own institutions, but the institutions in their respective regions, according to Dr. Fay. “The United States is far and away the leader in science. We do the best science, we publish the most, and we have amazing institutions that support that science,” Dr. Fay said. “Where we need to focus is taking that science and transitioning it into economic impact. Other countries, such as Germany, China and others, have traditionally done a better job of taking science discoveries and creating ways to advance that science into the marketplace. We want our great science and all that public money to create public good and economic benefit here in the US.” Dr. Fay added that the NSF developed I-Corps to teach scientists at universities how to explore the potential real-world applications of their research, discover organizations in the public and private sectors that might be interested in bringing those discoveries into fruition, and learn what value and what problems their research might solve.

There are a total of 16 higher-education institutions Involved in the Great Lakes I-Corps Hub based at U-M. “We’ve grown tremendously in terms of the number of teams that progress through a program,” Dr. Fay said. “I think we’re just shy of 600 teams and technologies that will be assessed through the program this year, involving more than 1,000 people–many of whom go on to start companies or see their ideas implemented through employment at established companies..” Dr. Fay noted that as a regional effort, I-Corps can access networks of people, money and resources that extend far beyond what any single institution could do on its own.

“In terms of the goals of I-Corps, the first one is to create a culture of impact and engagement between academia and the outside world,” he

said. “The other one is to create feedback. We need information to move from industry back into academia about where the problems are, so it’s not just “knowledge or technology push” where academics have to hope that industry will read their latest paper or license some new invention.Through the interactions in the program, academic researchers find out firsthand what struggles, challenges and gaps exist.

This discovery process and two way information exchange generates new use-inspired research ideas and over time, even more impactful discoveries. ” Dr. Fay added that another major goal of the program is to educate future leaders in science and technology on how to be change agents. “The vast majority of PhD students and postdocs end up in industry, and if they really embrace this entrepreneurial mindset of identifying the customer, finding the value proposition and listening to customer needs, they’ll be much more successful professionally,” he said.“They’ll be able to influence and create positive change in their organizations.

We also want to make sure that historically underrepresented groups in entrepreneurship see a pathway for their innovations and ideas to be developed. So we work hard to create a welcoming and inclusive environment so that everyone will be comfortable bringing in their goals and ideas.”

Dr. Fay’s addition to the BME team allows researchers in the department to contribute to and benefit from the I-Corps program. “I would say a good third to half of the I-Corps teams are using technology in healthcare,” he said. “We can then connect our own faculty to these teams to get their own ideas out there or connect with collaborators. We can leverage the infrastructure s and relationships that have been built for I-Corps for the benefit of our own faculty so that we’re better at getting our research out into the broader community.”

Dr. Fay noted there is “great synergy” between the I-Corps program and the Coulter Translational Research Partnership Program.

“They actually do very different things,” Dr. Fay said. “I-Corps is all about understanding

the stakeholders and their needs around and idea.. Coulter is about reducing the risk of that technology to do that, so they’re very complimentary in terms of the things that they do.”

BME alumni are invited to become involved with I-Corps. “We need alumni willing to be interviewed by our students and faculty to help them understand where the issues and problems are.. One of the biggest difficulties is getting access to information that can guide the development of these early stage technologies..

What is that first burning application that this new technology can be applied to?”

Dr. Fay said that mentorship is the second key area where alumni can contribute. “For those alumni who have experience running a startup or commercializing life-science technologies, we are always looking for experienced people that can help I-Corps participants on their way,” he said. “We’re building a mentor network to do this very task, so we need alumni to step forward and say they would love to be contacted and help out.”

Dr. Fay noted that the third area where alumni can assist is “of course, people in positions to fund these projects, either as venture capitalists, angel investors, corporate research & development folks, etc., who want to become more aware of the different projects and are interested in financially supporting them are always welcome. At the end of the day, without capital, these projects will remain ideas and never make it into use.”

Society’s pivot to remote connections has the opportunity to benefit I-Corps. “We need to take advantage of this brave new virtual world,” Dr. Fay said. “Frankly, I don’t think people understand the power of just 30 minutes. A 30-minute conversation with the right person who confirms a hypothesis or leads a discussion in a different direction can be life-changing.

Suddenly, a project that wasn’t going anywhere transforms into a project that has a lot of attention and has a real potential to change the world. And it’s just 30 minutes. All we need is 30 minutes of your time to talk to a researcher or a student and ignite that spark.”

BME innovations

BME SENIOR SERVES AS PRESIDENT OF U-M SOCIETY OF HISPANIC PROFESSIONAL ENGINEERS STUDENT CHAPTER

GIULIANA FAGRE GUERRIERO

STORY BY MICHELE SANTILLAN Giuliana Fagre Guerriero is a BME senior leading U-M’s student chapter of the Society of Hispanic Professional Engineers (SHPE).

“Our goal is to empower the Hispanic community to realize its potential and to impact the world through STEM awareness, access, support and development,” Fagre Guerriero said. “We provide many social, academic and professional activities to engage our members in the community and on campus, and to contribute to their overall academic development.”

Fagre Guerriero transferred to U-M two years ago, halfway through her sophomore year in college. During her junior year, she became the marketing director for SHPE, handling marketing and social media.

“We’re open to anyone on campus,” she said. “SHPE is really for everyone in STEM or engineering or in the Hispanic community.” The U-M chapter, which is one of the larger student chapters in the Midwest, has about 100 total members. In addition to Fagre Guerriero on the leadership board, one of SHPE’s academic directors is also a BME major.

Fagre Guerriero views her role as making the university and the student experience more

inclusive. “I think biomedical engineering is a very dynamic field,” she said. “In engineering, we learn many skills that can translate into different roles. I feel that all of my organizational skills and the way I think about certain things have helped me in the presidential role, from how to increase productivity to maintaining our mission and making sure that we’re standing by our purpose on campus, which is to make it an inclusive community and make the university feel smaller and more welcoming.”

Fagre Guerriero said one of her goals is to increase student participation, but her efforts extend beyond that to encourage members to consider BME, engineering and STEM fields for their careers or professions. “We have many incoming freshmen and sophomores who are still deciding their majors, and we have different programs within SHPE that can help them decide which track to pursue in engineering,” she said. “We also have mentorship activities that pair underclassmen and upperclassmen with similar backgrounds to help guide them towards their career plans. SHPE hosts study jams every week with the National Society of Black Engineers (NSBE) chapter as well. This is an opportunity to get to know other people

while also doing your homework and getting some tutoring advice.”

The SHPE chapter attended the national conference in Salt Lake City, Utah, in November and also hosts an annual event called SHPE’d Abroad. “At the end of the academic year, we will travel to a country in Latin America and do volunteer work with high school students to teach them about STEM and encourage them to pursue a career in engineering,” Fagre Guerriero said. “This past May, we went to the Dominican Republic for a week. I think that’s unique because we are one of the only–if not the only–SHPE student chapter in the nation that has such a coordinated volunteer program for global outreach.”

Fagre Guerriero said the trip is an important way to connect to the Hispanic community. “I remember at the time I was taking a Histology class about cells, and I showed scans of cells and how to identify the different cells in the body to the students,” she said. “They were perplexed by that. It was cool to bring that opportunity to a community for the first time and see that experience through someone else’s eyes, like it was once new for me.” Planning is already under way for the 2024 U-M SHPE trip to Costa Rica.

PHOTOS FROM THE DOMINICAN REPUBLIC:

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U-M BME PHD STUDENT MARIANA MASTELING RECEIVES TWO HONORS AT RECENT ASB CONFERENCE

MARIANA MASTELING

STORY BY MICHELE SANTILLAN Congratulations to U-M BME PhD recent graduate Mariana Masteling for recently receiving two awards at the American Society of Biomechanics (ASB) conference in Knoxville, Tennessee.

Masteling won the Clinical Biomechanics Award for “Two minutes is sufficient to characterize the viscoelastic properties of the lower human birth canal during the first stage of labor.” Her collaborators were John O.L. DeLancey, the Norman F. Miller Professor of Gynecology at the University of Michigan Medical School and the Director of Pelvic Floor Research in the Department of Obstetrics and Gynecology; and BME’s James A. Ashton-Miller, Associate Chair for Translational Research, Albert Schultz Collegiate Research Professor and Distinguished Research Scientist, Biomedical Engineering, Research Professor, Biomedical Engineering, R e s e a rc h P ro fe s s o r, M e c h a n i c a l Engineering, Research Professor, Internal Medicine, and Research Professor, Institute of Gerontology, who are the founders of the U-M Pelvic Floor Research Group, the first such group in the world established to identify risk factors for developing pelvic floor disorders, work with high-risk women to prevent them, and provide the most effective and newest treatments for pelvic floor dysfunction. The group hosts a Pelvic Floor Research Day early each year, attracting approximately 70 global participants.

Masteling also won first place in the Three Minute Thesis Graduate Competition at the ASB conference.

Dr. Ashton-Miller described Masteling’s research as “significant” because no one currently measures the viscoelastic properties of the lower birth canal in living women. “The lower birth canal is the main impediment to vaginal delivery because, as we have earlier shown, its tissues have to stretch over three-times their original length,” Dr. Ashton-Miller said. “Too stiff and/ or too viscous, and vaginal delivery of the

fetus is impossible, so both fetus and mother can die without a c-section; a little less stiff, and the second stage of labor will be too long, thereby placing fetus and/or mother at risk for injury. So if one can measure how ‘stretchy’ the tissue is before the second stage begins, the clinician and mother can decide either that there is no cause for concern (which happily is the case for ~80% of women) or, if it is too stiff, they can discuss interventions to help deliver the baby.”

Dr. Ashton-Miller added that, in one chapter of her dissertation, Masteling provides the first-ever data that establish the normal distribution, and importantly the mean + 3* standard deviation of lower birth canal stiffness and viscosity values, providing the foundation to establish the first lower-birth-canal screening test for unusually stiff or viscous birth canal tissue.

“This will open the way for physicians and midwives to identify those at risk and also new medical interventions to ripen its tissues in an analogous manner to those that can help ripen the cervix,” Dr. Ashton-Miller said.

“In addition, it facilitates new research into the mechanobiology of the birth canal ripening process. Other chapters employ theoretical models to help provide the means to predict who is at risk for unduly long labors and/ or injury.”

Masteling contacted Dr. Ashton-Miller in 2014 from the University of Porto in Portugal, asking to conduct research for her Master’s degree in his Biomechanics Research Laboratory at U-M. “ I accepted her because she was the first woman in 150 years to play the euphonium in her local band, had switched from studying medicine to engineering, and was a strong candidate for a Fulbright Award to support herself while studying with me,” he said.

“Despite the challenges of the Covid pandemic, Mariana persisted and, among others, worked with scientists from the University of Cambridge in implementing her theoretical models of lower birth canal

viscoelastic properties,” Dr. Ashton-Miller said. “Meanwhile, she has consistently provided technical support to U-M Obstetrics and Gynecology for MRI and ultrasound image analysis, as well as the U-M School of Nursing in developing a physical model to teach midwives about cervical ripening. During her doctorate she also provided technical and other mentorship to ten undergraduate and graduate students, several Ob-Gyn medical residents and fellows, routinely shared her algorithms on Github for others to use, all the while being active in community service outside the university.”

“For much of her doctorate in biomedical engineering at U-M, Mariana was supported

by National Institutes of Health (NIH) Small Business Innovation Research (SBIR) Fastrac funds, which we had suggested a Stanford startup company, Materna Medical, LLC, should apply for given they wanted to collaborate,” Dr. Ashton-Miller added.

“The company went on to raise significant venture capital support to run the ongoing EASE clinical trial for its PREP vaginal dilation device at 15 medical centers around the United States. Throughout we have enjoyed a close and productive collaboration with Materna. Part of Mariana’s dissertation involved analyzing the biomechanics data gathered by the PREP device during the first stage of labor. She presented the results from the first 56 women at the 2023 national meeting of maternal fetal medicine specialists in San Francisco early this year.

The EASE trial is scheduled to conclude later this year after enrolling 200 women.“ Dr. Ashton-Miller concluded: “Mariana’s dissertation is some of the most important doctoral research to come out of my laboratory since I joined U-M in 1983. She is bringing uncommon recognition to the University of Michigan in her field and represents the very best of our graduate students.”

BME innovations

BME STUDENT EXPLORES WAYS TO ASSIST PEOPLE WITH DEVELOPMENTAL DISABILITIES THROUGH TECHNOLOGY

NIKHIL MANTENA

STORY BY MICHELE SANTILLAN BME undergrad student Nikhil Mantena has turned his volunteer experiences as a teen into a lifelong goal: Focusing on digital health and education to assist people with intellectual and developmental disabilities.

Mantena devoted his time to helping people who face these challenges, starting with his involvement in high school. “I was volunteering for a nonprofit in the southeast area of Detroit, where I’m from,” he said. “I was tutoring a man named Jeff, who was nonverbal and had other intellectual and developmental disabilities, or IDDs. Over the next four years, I was really focused on teaching him how to communicate using his iPad. So, that’s where I became very interested in this topic. I was spending a lot of time, pretty much every week, helping him for at least two hours at a time. I slowly taught him to use his iPad to not only FaceTime his parents, but to talk to his friends and communicate with his caretakers.”

During college, Mantena has used that experience as an inspiration for a startup called Tech Buddies, which is focused on teaching people with different disabilities.

“What we’re doing is trying to use a unique method of abstraction of knowledge to cater to their needs a little better,” he added.

Mantena’s passion has extended beyond Tech Buddies, and he is now working on finding job opportunities for the community as well. Ultimately, his vision is to modernize education systems and also provide lifestyle support. ““Our guiding principle is to truly understand the individualized needs of people with disabilities and provide tailored

platforms that support autonomous living,” Mantena said. “One of the main goals is to really focus on modernizing special education curricula for communication and to include digital means of communication within that umbrella because oftentimes it’s not a part of the plan. That’s the real goal and evolution that we’re hoping to achieve.

I’d like to say that we’re stepping in the right direction.”

Mantena is working on an employment agency called MoJo, which stands for “more jobs.” The organization’s goal is to achieve greater employment opportunities for people with cognitive disabilities. “Currently, only 19 percent of people with this type of disability are currently employed, and many are employed for under minimum wage,” Mantena said. “Our entire mission statement is to increase opportunities and to be sure that those opportunities are above minimum wage so workers can support themselves and live autonomous lives.”

Mantena has a team of people working with him on Tech Buddies and MoJo. “We have a neurologist on the team, an autism coach, a former principal, and also a person who was involved with Angel Place, the nonprofit I was working with in high school,” Mantena said. “For MoJo, I’m currently working with a student on campus who co-founded it with me. One of the biggest things I’ve been trying to do is to try to find people with similar interests to assist. Many of us have a loved one who is affected by this disability, and so it can touch home very quickly, just given how frequently it gets diagnosed. However, this issue is something

that often gets overlooked in society. We’re trying to raise awareness about how technological interventions coupled with human interactions can change the direction of people’s lives for the better.”

Mantena’s BME journey has been focused on neural engineering, and he is currently working in Prof. Enrico Opri’s lab on research related to treatments for people with neurodegenerative diseases. ““My main goal is to merge both my educational work for people with IDDs and my engineering research utilizing virtual reality and surgical procedures to enhance the quality of life for patients,” Mantena said. “I want to be able to create better systems that are able to serve people.”

Mantena’s long-term goal is to become a doctor, working in this area and innovating new technologies for health care settings and novel therapies to improve patient outcomes. “I want to create and use technology to educate our medical professionals on how to interact with people with disabilities and provide a higher standard of care. By implementing groundbreaking technologies into healthcare, we can ‘techify’ the industry and enhance the experience for providers, patients, and families. I want to become a doctor to not only serve people on an individual basis but to improve the overall system.”

For those who would like to become involved in this area, Mantena has a Tech Buddies website with a contact form. To get involved with Tech Buddies or MoJo, please contact Mantena at nmantena@umich.edu.

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D ONOR H O N O R R O L L BME is grateful to our generous donors fo r their commitment to our department’s mission. Our donors’ contributions have touched the lives of our faculty, staff and students and have allowed us to provide for the expansion of BME initiatives. Biomedic al Engineering was the 10th most popular major on U-M’s Ann Arbor c ampus in 2022. Donor support is critic al in helping us s erve our growing student population. From the bottom of our hearts, thank you, and Go Blue!

T his D o no r H o no r Roll i n c lu d e s d on at i on s m ad e from Jul y 1 , 20 2 1 , through O ctobe r 1 5 , 20 23 .

Anonymous Donors Adobe Systems, Inc. Karl and Patricia Betz Herbert and Zanita Buchanan John and Katherine Campbell Cynthia Caraballo-Hunt and Steven Hunt J. Scott Carr and Marion E. Parr Jessie Carr Raquelle Carter Mindy Chilman Jack DeVries Edmonson Family Jiao Fan and Jane Gao Edward R. Feldman* Ilene and Timothy Flanagan Spencer Ford and Susan Goldsmith Karen Gates Genentech Foundation Jay and Susan Goldberg Michael Gresens and Marcia Bratschi Jay and Nancy Hall HistoSonics, Inc. John C. and Carolyn Hogan Susan Hunt David Kim Jung Gyun Kim, Synpath Shira Lehmann Joel Leonard Robert and Patricia Lerner Qingyuan Li and Quan Zheng Xiaoming Liu and Li Zhao David and Cindy Louwsma

Frode Maaseidvaag Shaun McManimon Carl Moline Mary-Ann Mycek and John Card Novartis US Foundation Nancy Okstein Rebecca Palmer Keith and Nancy Peyton Timothy and Ilona Philippart Hugh and Joan Phillips Michael and Sharlene Ransford Suzanne and Brian Ross Holly and William Russell Stuart Schlitt Joshua and Suzanne Secrest Joseph Serritella and Elizabeth McCaffrey Lisa Smerdon Howard and Susan Smith Susan and Stephen Smith Susan and Michael Soltys Michael and Joan Stern Richard and Diane Stribley Peggy Su and Gerard Luk Pat Zhihong Su and Helios Leung Brian Xiaobo Sun Allison and Justin Sweet Timothy Tran Kristen Wolff Hong Xiao and Chaoyu Jin Honglei Yu and Wen Chen Edward Zhang

* = PL ANNED GIVIN G D ON OR

BME innovations

M AK E A DIF F EREN C E— SU PPORT U- M BIO MEDIC A L E NGINE ERIN G As a BME alum, perhaps you remember a favorite professor or class? Maybe your son or daughter’s curiosity was sparked through a research project that led them to declare BME as their major? Maybe you are involved in the BME profession and want to encourage the next generation of leaders to explore our field?

For those reasons and more, we are grateful to our readers who have given their time, talent and treasure to support U-M BME’s ongoing activities. Our faculty, staff and students appreciate your continued generosity.

Your support helps us continue our mission of educating the next generation of the leaders and best in the biomedical engineering community. Donations to our various funds support scholarship opportunities for first-generation students and students from historically underrepresented communities. Donor support has helped us strengthen our programming and activities that we can offer through student organizations and research opportunities, and has helped us ensure we have modernized facilities that foster the collaborative spirit needed for success in industry and academia today.

“The sense of community in BME is one of the main reasons I decided to come to Michigan,” said BME alum Elizabeth Bottorff.

“During my time at Michigan, I had a lot of opportunities to get involved with the department, and I’ve seen firsthand how your donations translate into improved programming and events that help keep our sense of community strong, especially as our numbers continue to grow. With that, I want to say thank you and Go Blue!”

“These donations help support graduate students, such as myself, throughout our academic training,” said PhD student Nicholas Schott. “Instead of worrying about how to fund our studies, we can focus on bigger questions at hand, such as ‘What stem cells will we use when growing a new heart?’ ” PhD student Lauren Madden also expressed her gratitude for donor support. “I want to emphasize what a huge impact donations have had on our students in the Biomedical Engineering program,” she said. “It is so important to foster the education of STEM students who will pursue careers that will help improve the field of medicine and develop new solutions to health issues that affect people throughout the world.”

Please consider a gift to the BME Impact Fund. Use the giving link or instructions below to make your gift. Your support means the world to our BME community. As all of our students said, thank you, and Go Blue!

To donate online, please use this link or the QR code: Link: https://donate.umich.edu/MZBW4 Gifts via check can be mailed to the following: Check payable to: “University of Michigan” Memo line: “BME IMPACT FUND” Mail to: University of Michigan College of Engineering 1221 Beal Avenue Suite G264 Ann Arbor, MI 48109

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I N MEMO R I A M PROFESSOR R AOU L KOP E L M A N

U-M BME was saddened to learn about the passing of Professor Raoul Kopelman. Professor Kopelman (1933 to 2023) passed away in Ann Arbor on July 20 at the age of 89. He was a jointly appointed professor of biomedical engineering from 2006 until 2014 and remained an active member of our faculty until his passing.

Professor Kopelman was born in Vienna, Austria, on October 21, 1933. He earned his BS in Chemical Engineering at the Technion, Israel Institute of Technology (1955), as well as an Engineering Diploma (1956) and an MS in Physical Chemistry (1957). He was the first Israeli to receive the US Fulbright Travel Grant (1957). Professor Kopelman earned his Chemistry PhD at Columbia University (1960) and completed his postdoctoral training at Harvard (1960-62).

“Dr. Kopelman was a wonderful colleague with whom Raoul Kopelman. Professor Kopelman 1933-2023. He was the The Richard Smalley Distinguished University Professor of Chemistry, Physics, Applied Physics, Biophysics, Biomedical Engineering and Chemical Biology. our faculty often collaborated, including on dissertation committees and research projects,” said Mary-Ann Mycek, the William and Valerie Hall Department Chair of Biomedical Engineering and Professor, Biomedical Engineering. “He had a generous nature and enjoyed sharing his love of learning with our community. He will be greatly missed.”

Dr. Kopelman became an expert on photonics, laser and bioanalytical chemistry, chemical physics, catalysis, nano-materials and nano-devices. He was a professor at the University of Michigan for 57 years (1966-2023); the Richard Smalley Distinguished University Professor of Chemistry, Physics, Applied Physics, Biophysics, Biomedical Engineering and Chemical Biology; Member of The Michigan Nanotechnology Institute for Medicine and Biological Sciences, The Michigan Biointerfaces Institute, and The Rogel Cancer Center.

He mentored more than 70 PhD students in Biomedical Engineering, Chemistry, Physics, Biophysics and Applied Physics, who launched successful academic careers as professors at primary universities or pursued excellence in industry and government. Professor Kopelman has been celebrated for his leadership, research, and educator role in the materials nanoscience community, for key developments in percolation theory applications and fractal kinetics, and for developing nanochemistry and nanobiochemistry scientific paradigms and tools, integrating these into nanomedicine to treat life-threatening diseases.

“Dr. Kopelman was a wonderful scientist and mentor,” said former student Ariel Hecht (BME, PhD, 2013). “I will always remember his love and enthusiasm for science — he was genuinely passionate for his work. He also fostered a lab environment where students were encouraged to independently explore ideas, and he was very supportive of trying new things; I personally benefited a lot from this approach. He focused on what was most important, provided me with great feedback and mentorship, and encouraged me to graduate and move on to the next step when the time was right. I am very grateful for having been in his lab for five years, and will miss him greatly.”

Former biomedical engineering student Irene Sinn (PhD, 2012) added: “In the wake of Professor Raoul Kopelman’s loss, we celebrate a unique individual who was more than a scientist; he was an exceptional mentor and friend,” she said. “I was honored to have Professor Kopelman as my co-advisor during my time at University of Michigan – he crafted my intellect and fostered my growth into a thoughtful scientist and empathetic person.

The global scientific community, together with our UM family, mourns his departure but cherishes his profound influence. His legacy is not confined to his scholarly work; it echoes in his students and colleagues, in our values, and in the way we approach our respective fields. We honor his memory by perpetuating his dedication to science.

Remembering Professor Kopelman, we recall his brilliance, honesty, and kindness that touched so many lives. His lasting impact in science and mentorship will inspire future generations.”

BME extends our condolences to Professor Kopelman’s family, friends, colleagues and former students on his loss.

BME innovations

CO RE FACU LT Y

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CO RE FACU LT Y

BME innovations

ASS O C I AT E FAC ULT Y Gorav Ailawadi, M.B.A., M.D. Professor & Chair, Cardiac Surgery Professor, Biomedical Engineering Ellen Arruda, Ph.D. Tim Manganello / BorgWarner Department Chair Maria Comninou Collegiate Professor, Mechanical Engineering Professor, Biomedical Engineering Daniel Beard, Ph.D. Carl J. Wiggers Collegiate Professor of Cardiovascular Physiology Professor, Molecular & Integrative Physiology Professor, Internal Medicine Professor, Emergency Medicine Professor, Biomedical Engineering Omer Berenfeld, Ph.D. Professor, Internal Medicine Professor, Biomedical Engineering Amanda Kiely Bicket, M.D., M.S.E. Assistant Professor, Ophthalmology & Visual Sciences Assistant Professor, Biomedical Engineering Mark Burns, Ph.D. Professor, Biomedical Engineering Professor, Chemical Engineering T. C. Chang Professor of Engineering Paul Cederna, M.D. Professor, Biomedical Engineering Robert Oneal Collegiate Professor of Plastic Surgery, Department of Surgery Luyun Chen, Ph.D. Associate Research Scientist, Obstetrics and Gynecology Associate Research Scientist, Biomedical Engineering Omolola Eniola-Adefeso, Ph.D. Associate Dean for Graduate & Professional Education Vennema Endowed Professor, Chemical Engineering University Diversity and Social Transformation Professor of Chemical Engineering Professor, Biomedical Engineering Mario Fabiilli, Ph.D. Associate Professor, Radiology Associate Professor, Biomedical Engineering

Jeffrey Fessler, Ph.D. Professor, Biomedical Engineering William L. Root Collegiate Professor, Electrical Engineering & Computer Science Professor, Radiology J. Brian Fowlkes, Ph.D. Professor, Radiology Professor, Biomedical Engineering Luis Hernandez-Garcia Research Professor, Radiology Research Professor, Biomedical Engineering Deanna Gates, Ph.D. Associate Professor, Movement Science Associate Professor, Biomedical Engineering Karl Grosh, Ph.D. Professor, Biomedical Engineering Professor, Mechanical Engineering Vikas Gulani, M.D., Ph.D. Fred Jenner Hodges Professor and Chair, Radiology Professor, Biomedical Engineering Alfred Hero, Ph.D. Professor, Biomedical Engineering Professor, Electrical Engineering & Computer Science Professor, Statistics Jane Huggins, Ph.D. Associate Research Scientist, Physical Medicine & Rehabilitation Associate Research Scientist, Biomedical Engineering

Chandramouli Krishnan, Ph.D. Associate Professor, Physical Medicine & Rehabilitation Associate Professor, Biomedical Engineering Associate Professor, Robotics Associate Professor, School of Kinesiology Joerg Lahann, Ph.D. Professor, Chemical Engineering Professor, Biomedical Engineering Professor, Materials Science and Engineering Lisa Larkin, Ph.D. Professor, Molecular and Integrative Physiology Professor, Biomedical Engineering Somin Lee, Ph.D. Assistant Professor, Electrical Engineering and Computer Science Assistant Professor, Biomedical Engineering Sasha Cai Lesher-Pérez, Ph.D. Assistant Professor, Chemical Engineering Assistant Professor, Biomedical Engineering Jennifer Linderman, Ph.D. Professor, Biomedical Engineering Professor, Chemical Engineering Allen Liu, Ph.D. Associate Professor, Mechanical Engineering Associate Professor, Biomedical Engineering

Karl Jepsen, Ph.D. Associate Dean for Research, Professor of Orthopaedic Surgery, Medical School Professor, Biomedical Engineering

Claudia Loebel, M.D., Ph.D. Assistant Professor, Materials Science and Engineering Assistant Professor, Biomedical Engineering

Jacqueline Jeruss, Ph.D., M.D. Professor, Surgery Professor, Biomedical Engineering Professor, Pathology

Gary Luker, M.D. Professor, Radiology Professor, Microbiology and Immunology Professor, Biomedical Engineering

Kenneth Kozloff, Ph.D. Steven A. Goldstein, PhD, Collegiate Professor in Orthopaedic Surgery Professor, Biomedical Engineering

Peter Ma, Ph.D. Richard H. Kingery Endowed Collegiate Professor, Biologic and Materials Sciences, School of Dentistry Professor, Materials Science and Engineering, Professor, Biomedical Engineering

Oliver Kripfgans, Ph.D. Associate Professor, Radiology Associate Professor, Biomedical Engineering

Tristan Maerz, Ph.D. Assistant Professor, Orthopaedic Surgery, Assistant Professor, Internal Medicine, Assistant Professor, Biomedical Engineering

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62 | BME innovations James Moon, Ph.D. J. G. Searle Professor, Pharmaceutical Sciences Professor, Biomedical Engineering Sunitha Nagrath, Ph.D. Professor, Chemical Engineering Professor, Biomedical Engineering Jon-Fredrik Nielsen , Ph.D. Research Associate Professor, Radiology Research Associate Professor, Biomedical Engineering Parag Patil, Ph.D., M.D. Associate Professor of Neurosurgery, Neurology, Anesthesiology and Biomedical Engineering Yannis M. Paulus, F.A.C.S., M.D. Associate Professor, Ophthalmology and Visual Sciences Associate Professor, Biomedical Engineering Scott Peltier, Ph.D. Research Scientist, Radiology Research Scientist, Biomedical Engineering Steven Schwendeman, Ph.D. Chair and Ara G. Paul Professor, Pharmaceutical Sciences Professor, Biomedical Engineering Nicole Seiberlich, Ph.D. Professor, Radiology Professor, Biomedical Engineering Albert Shih, Ph.D. Professor, Biomedical Engineering Professor, Mechanical Engineering Jason R. Spence, Ph.D. H. Marvin Pollard Collegiate Professor of Gastroenterology Professor, Internal Medicine Professor, Cell & Developmental Biology Professor, Biomedical Engineering

Thomas Wang, M.D., Ph.D. Professor, Internal Medicine Professor, Biomedical Engineering Professor, Mechanical Engineering H. Marvin Pollard Collegiate Professor of Endoscopy Research Kevin R. Ward, M.D. Professor, Emergency Medicine Professor, Biomedical Engineering

Nicholas Burris, M.D. Assistant Professor of Radiology Yue Cao, Ph.D. Professor, Radiation Oncology Jiande Chen, Ph.D. Professor, Division of Gastroenterology and Hepatology, Internal Medicine

Margaret Westfall, Ph.D. Associate Professor, Surgery/Cardiac Surgery Section Associate Professor, Molecular and Integrative Physiology Associate Professor, Biomedical Engineering

Rodney C. Daniels, M.D. Assistant Professor, Pediatric Critical Care Medicine

Euisik Yoon, Ph.D. Professor, Electrical Engineering & Computer Science Professor, Biomedical Engineering

Joseph Decker, Ph.D. Assistant Professor, Cariology Assistant Professor, Restorative Sciences Assistant Professor, Endodontics

A FFILIATE FACULTY

Kamran Diba, Ph.D. Associate Professor, Anesthesiology

Omar Ahmed, Ph.D. Assistant Professor, Psychology & Neuroscience Jaimo Ahn, M.D., Ph.D. Gehring Professor, Orthopaedic Surgery Larry Antonuk, Ph.D. Professor, Radiation Oncology Thomas Armstrong, MPH, Ph.D. Professor, Industrial & Operations Engineering Ryan Bailey, Ph.D. Robert A. Gregg Professor, Department of Chemistry James Baker Jr., M.D. Ruth Dow Doan Professor, Internal Medicine Professor, Internal Medicine

William Stacey, M.D., Ph.D. Professor, Neurology Professor, Biomedical Engineering

James Balter, Ph.D. Professor, Radiation Oncology

Muneesh Tewari, Ph.D., M.D. Ray and Ruth Anderson-Laurence Sprague Memorial Research Professor Professor, Internal Medicine Professor, Biomedical Engineering

Marco C. Bottino, D.D.S., MSc., Ph.D. Associate Professor, Department of Cariology Associate Professor, Restorative Sciences Associate Professor, Endodontics

Greg Thurber, Ph.D. Associate Professor, Chemical Engineering Associate Professor, Biomedical Engineering

David T. Burke, Ph.D. Professor, Department of Human Genetics

Timothy Chupp, Ph.D. Professor, Physics

Mark Draelos, M.D., Ph.D. Assistant Professor, Robotics Assistant Professor, Ophthalmology Renny Franceschi, Ph.D. Professor, Dentistry Professor, Biological Chemistry Jianping Fu, Ph.D. Professor, Mechanical Engineering Professor, Cell & Developmental Biology Shinichi Fukuhara, M.D. G. Michael Deeb, M.D. and Nancy Deeb Research Professor, Cardiac Surgery Craig Galbán, Ph.D. Professor, Radiology Lana Garmire, Ph.D. Associate Professor, Computational Medicine and Bioinformatics Associate Professor, Biostatistics Mitchell Goodsitt, Ph.D. Professor of Radiological Sciences, Radiology Robert Gregg, M.S., Ph.D. Associate Professor, Electrical Engineering & Computer Science Hitinder Gurm, M.D. Professor of Medicine, Cardiovascular Medicine

BME innovations Jesse Hamilton, Ph.D. Assistant Professor, Radiology Kurt Hankenson, Ph.D., D.V.M. Professor, Orthopaedic Surgery Diane Harper, M.D., M.S., MPH Professor, Family Medicine Professor, Obstetrics and Gynecology Idse Heemskerk, Ph.D. Assistant Professor, Cell and Developmental Biology Anthony Hudetz, Ph.D. Professor, Anesthesiology Richard Hughes, Ph.D. Associate Professor, Orthopaedic Surgery Associate Professor, Industrial & Operations Engineering Yun Jiang, Ph.D. Assistant Professor, Radiology Ajit Joglekar, Ph.D. Associate Professor, Cell and Developmental Biology Darnell Kaigler, Jr., Ph.D., D.D.S., M.S. Assistant Professor, Dentistry Assistant Professor, Periodontics Assistant Professor, Oral Medicine

Christian Lastoskie, Ph.D. Associate Professor, Civil and Environmental Engineering Daniel Leventhal, Ph.D., M.D. Assistant Professor, Neurology Xiaoxia Lin, Ph.D. Assistant Professor, Chemical Engineering Changyang Linghu, Ph.D. Assistant Professor, Cell and Developmental Biology David Lipps, Ph.D. Associate Professor, Movement Science Isabelle Lombaert, M.S., Ph.D. Associate Professor, Biologic and Materials Sciences Pedro Lowenstein, M.D., Ph.D. Professor, Neurosurgery Richard Schneider Collegiate Professor of Neurosurgery Professor, Cell and Developmental Biology Anahita Mehta, Ph.D. Assistant Professor, OtolaryngologyHead and Neck Surgery Edgar Meyhofer, Ph.D. Professor, Mechanical Engineering

Kimberlee Kearfott, Sc.D. Professor, Nuclear Engineering and Radiological Sciences Adjunct Professor, Radiology

Jouha Min, Ph.D. Assistant Professor, Chemical Engineering

Stephen Kemp, Ph.D. Assistant Research Professor, Surgery

Stephanie Moon, Ph.D. Assistant Professor, Human Genetics

Megan Killian, M.S., Ph.D. Assistant Professor, Orthopaedic Surgery

Jacques Nor, D.D.S., M.S., Ph.D. Donald A. Kerr Professor, Dentistry Professor, Otolaryngology

Jinsang Kim, Ph.D. Professor, Materials Science and Engineering Professor, Chemical Engineering Professor, Chemistry Nicholas Kotov, Ph.D. Professor, Chemical Engineering Ron Larson, Ph.D. George Granger Brown Professor, Chemical Engineering A.H. White Distinguished University Professor, Mechanical Engineering

Gabe Eston Owens, M.D., Ph.D. Clinical Associate Professor, Pediatric Cardiology Joseph Potkay, Ph.D. Assistant Research Professor, Surgery Indika Rajapakse, Ph.D. Professor, Computational Medicine & Bioinformatics Professor, Mathematics Ayyalusamy (Rams) Ramamoorthy, Ph.D. Robert W. Parry Collegiate Professor of Chemistry and Biophysics

Arvind Rao, Ph.D. Associate Professor, Computational Medicine and Bioinformatics, Radiation Oncology William Woodruff Roberts, M.D. Professor, Urology Kathleen Sienko, Ph.D. Arthur F. Thurnau Professor, Mechanical Engineering Tomer Stern, M.S., Ph.D. Assistant Professor, Biologic and Materials Sciences & Prosthodontics Peter Tessier, Ph.D. Albert M. Mattocks Professor of Pharmaceutical Sciences, Chemical Engineering J. Scott VanEpps, Ph.D., M.D. Associate Professor, Emergency Medicine Associate Professor, Macromolecular Science and Engineering Angela Violi, Ph.D. Professor, Chemical Engineering Professor, Mechanical Engineering Professor, Biophysics Henry Wang, Ph.D. Professor, Chemical Engineering Zhong Wang, Ph.D. Professor, Cardiac Surgery Brendon Watson, Ph.D., M.D. Assistant Professor, Psychiatry Pamela Wong, Ph.D. Research Assistant Professor, Internal Medicine

Qiong Yang, Ph.D. Associate Professor, Biophysics Associate Professor, Physics Bo Yang, M.D. Frankel Research Professor of Aortic Surgery J Maxwell Chamberlain M.D. Collegiate Professor, Cardiac Surgery Ron Zernicke, D.Sc., Ph.D. Professor, Orthopaedic Surgery Professor, Kinesiology David Zopf, M.D., M.S. Assistant Professor, Otolaryngology Head and Neck Surgery

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NONPROFIT ORGANIZATION U.S. POSTAGE PAID ANN ARBOR, MI PERMIT NO. 144

1125 GERSTACKER, 2200 BONISTEEL BLVD., ANN ARBOR, MI 48109

EDITOR: MICHELE SANTILLAN DESIGN: MASON HINAWI