University of Notre Dame Bioengineering Annual Review | 2018

2018 ANNUAL REVIEW

IN THIS ISSUE

From the Director . . . . . . . . . . . . . . 2 Faculty News . . . . . . . . . . . . . . . . . . . 3 New Faculty . . . . . . . . . . . . . . . . . . . . 5 Student Spotlights . . . . . . . . . . . . . 6 Alumni Spotlights . . . . . . . . . . . . . . 7 Participating Faculty . . . . . . . . . . . 8

“Cardiac cells are natural oscillators, ... they beat spontaneously and, when coupled, they can synchronize to a locked, steady frequency.”

Zorlutuna Expands Research on Cardiac Cells Pinar Zorlutuna, associate professor of aerospace and mechanical engineering, directs the Tissue Engineering Laboratory where she explores biomimetic environments in order to understand and control cell behavior in conjunction with researchers in the College of Engineering, the Center for Stem Cells and Regenerative Medicine, and the Mike and Josie Harper Cancer Research Institute. The co-owner of two patents related to biomaterials and tissue engineering, she has received a number

of awards, including a 2017 National Science Foundation Early Career Development Award (NSF CAREER) for her project titled “Tissue-engineering an Aging Heart: The Effect of Aged Cell Microenvironment in Myocardial Infarction” and the 2016 Rising Star Award from the Biomedical Engineering Society.

Most recently, she has been leading a study of cardiac cells as an avenue to create a more nearly optimal computer network for solving complex problems. “Cardiac cells are natural oscillators,” says Zorlutuna. “They beat spontaneously and, when coupled, they

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can synchronize to a locked, steady frequency. What we want to find out is if we create a network using these bio-oscillators, will their natural spatiotemporal dynamics be able to solve complex problems optimally, in less time and using less energy than siliconbased digital computing hardware?”

Zorlutuna is also studying tumor growth and metastasis of cancer cells in stiffer breast tissue and how cancer cells interact with connective tissue to affect surrounding cells.

More information on her work in bioengineering can be found at tissueeng.nd.edu.

From the Director When we established the Bioengineering Graduate Program at Notre Dame in 2007, our vision was to provide a tailored educational experience for graduate students working at the interfaces of engineering, biology, and medicine that would lead to better student recruitment and retention. In 2011, we graduated our first students. Now, completing our 10th year, we are making a noticeable impact in research and education at Notre Dame and in the biomedical research community.

Both the number of students and the number of participating faculty have continued to expand. The program currently has 21 Ph.D. students who are advised by ten engineering faculty members across three departments. Several students are co-advised by engineering and science faculty. Four Ph.D. and one Master’s degree were awarded in the 2017-18 academic year, bringing our total number of Ph.D. graduates to 19.

The research portfolio of the program has also grown over the past decade from its original focus on orthopaedics to include tissue engineering, lab-on-a-chip, organ-on-a-chip, developmental and synthetic biology, immune therapies, imaging, and molecular development. These new and exciting research areas have been driven by new assistant professor-level hires in the electrical, chemical and biomolecular, and aerospace and mechanical engineering departments. The opening of the Harper Cancer Research Institute in 2011 resulted in a number of important collaborations with biologists and biochemists eager to apply new engineering approaches to basic and translational research studies.

In a challenging environment, participating faculty have successfully garnered research funding from a range of federal government, foundation, and industrial sources. Notably, Pinar Zorlutuna received a prestigious NSF CAREER award and Jeremiah Zartman was awarded an NIH MIRA grant. Recently, members of the program were selected to lead a stem cell manufacturing effort by the Advanced Regenerative Manufacturing Institute in collaboration with Louisiana State University and the University of Texas at Arlington. We are also excited to welcome Sangpil Yoon to our group, who comes with an NIH K99/R00 Pathway to Independence Award related to acoustic transfection. (See New Faculty on p.5) Starting our second decade, the Notre Dame Bioengineering Graduate Program is looking forward to continuing our momentum to develop a rich atmosphere where we can make an impact on the global biomedical and bioengineering community. We are also excited to play a central role in expanding both research and education on the Notre Dame campus.

Glen L. Niebur Professor, Aerospace and Mechanical Engineering Bioengineering Graduate Program Director Phone: 574.631.3327 Email: gniebur@nd.edu

About the ND Bioengineering Graduate Program The Bioengineering Graduate Program at Notre Dame is an interdisciplinary Ph.D. program based in the College of Engineering. It encompasses faculty from across the University with expertise in biomaterials, cancer, computational and systems biology, drug delivery and therapeutics, environmental science, genomics/DNA/RNA, health robotics and technology, imaging, mechanobiology and physical effects on cells, orthopaedics, regenerative medicine, rehabilitation and motor control, and sensors and diagnostics.

For information about the Notre Dame Bioengineering Program, visit: bme.nd.edu.

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Faculty News Zartman Receives NIH MIRA Award Jeremiah J. Zartman, associate professor of chemical and biomolecular engineering, was awarded a competitive Maximizing Investigators’ Research Award (MIRA, R35) grant from the National Institutes of Health.

The five-year grant titled “Regulation and Function of Multicellular Calcium Signaling in Epithelial Growth and Regeneration” is supporting the study of impaired cellular calcium signaling, which is prevalent in many diseases including skin disorders, Alzheimer’s, and metastatic cancer. When functioning properly, a cell’s internal “computer” uses calcium ions as messengers to help calculate its response to environmental stimuli. This requires regulation of calcium ion concentrations in cells to coordinate cellular processes.

However, much remains unknown about the functions of time-varying calcium signals in developing or regenerating organs.

Zartman’s work seeks to discover the biochemical and mechanical basis of integrative cell communication mediated by calcium signaling. A long-term goal of his research is to learn how to manipulate calcium signaling to control cell growth, motility, death, or function. This knowledge could shed light on new ways to target and destroy cancer cells or stop metastatic cells from spreading. The work could also inspire methods to regulate cell differentiation for stem cell engineering applications.

Zartman and Brandon Ashfeld, associate professor of chemistry and biochemistry at Notre Dame, have also recently received a Discovery Fund Award from Notre Dame’s Advanced Diagnostics and Therapeutics to design and develop a new therapeutic for trisomy 21 phenotypes, the most common form of Down syndrome.

Details on these projects and Zartman’s work in morphogenesis, growth, and regeneration, sites.nd.edu/zartmanlab.

Howard Leading Study on Super-resolution Microscopy in Living Tissue Scott S. Howard, associate professor of electrical engineering, is in the middle of his five-year NSF CAREER grant to study, develop, characterize, and evaluate a new method for super-resolution molecular imaging inside living organisms. The goal of the project, “Three-dimensional, Super-resolution, and Super-sensitivity Quantitative Multiphoton Microscopy in Living Tissue,” was to develop the first three-dimensional super-resolution microscopic imaging device that could be used to see molecules inside of living cells in vivid detail while also measuring the chemical concentrations within those cells. He and his team have accomplished this part of the project, called fluorescence lifetime imaging

microscopy (FLIM). While working on FLIM, they developed an additional super-resolution technique — stepwise optical saturation (SOS) microscopy — that can be accessed using a conventional fluorescence microscope.

The team has also created an app through which researchers can utilize the SOS method.

For more information, visit the Howard Research Group at ee.nd.edu/research-lab-websites/howardresearchgroup.

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Faculty News continued

NIH Collaboration between Notre Dame and Ohio State Yields Results … One Step at a Time

James Schmiedeler, professor of aerospace and mechanical engineering, and Kevin O’Brien, a Ph.D. student in the University’s Bioengineering Graduate Program, are collaborating with researchers in the NeuroRecovery Network at The Ohio State University to address the common walking challenges that both individuals who have experienced spinal cord injuries and biped robots face. O’Brien has completed a preliminary analysis of walking data comparing 13 individuals with

incomplete spinal cord injury (iSCI) to healthy control subjects, matched for age, body mass, and overground walking speed. Early results have identified persistent deficits in muscle control during the critical early portion of the “stance phase” of walking among the iSCI subjects. The results have also shown that after 12 weeks of downhill treadmill training [physical therapy] most of the iSCI subjects exhibit biomechanics via joint angles and power in that “stance phase” more similar to those of the healthy control group.

O’Brien is now generating computer simulations using the test subject data, including information from electromyo-

Notre Dame Bioengineering Faculty Awarded Advanced Regenerative Manufacturing Institute Project Currently, tissue engineered medical treatments and cell therapies rely on stem cells produced through small batch processes that are carried out by individuals in specialized facilities. The lack of scalability makes this approach untenable for real-world products. Moreover, even with the highest quality control

standards, there is considerable batch-to-batch variability.

Beginning in 2019 and under the project leadership of Richard E. Billo with ND Research, Professors Niebur, Zorlutuna, and Dervis Can Vural from the Department of Physics will lead the Notre Dame effort to characterize conditions that result in repeatable cell behavior, optimize the production rate, and allow continuous cell output.

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graphy (EMG) sensors, to replicate the overall biomechanics and known muscle activations. He has developed a novel approach to interpreting the EMG data that will make the simulations more reliable. This stage of the project is focusing exclusively on individuals in the chronic stage of iSCI. The next step in the project will focus on intervention for individuals in the acute phase, when changes in biomechanics are the most dynamic and therapies may have an even greater effect on walking.

For more information, visit amerobotics.nd.edu/projects/eccentricmodeling.html.

This is one of the first projects funded by the Advanced Regenerative Manufacturing Institute (ARMI). A Department of Defense sponsored National Network for Manufacturing Innovation institute, ARMI is headquartered in Manchester, N.H. (www.armiusa.org). The overall goal of the institute is to develop validated methodologies to manufacture cells and tissues that are applicable to regenerative medicine, thereby enhancing the ability to move these technologies from the laboratory to the marketplace.

New Faculty A faculty member since 2017, Assistant Professor Donny Hanjaya-Putra received his undergraduate degree in chemical and biomolecular engineering at Notre Dame and his Ph.D. at Johns Hopkins University. He also served as a postdoctoral research fellow in the Department of Surgery at Harvard Medical School and was recently named an “Emerging Leader in Biological Engineering” by the Journal of Biological Engineering.

Hanjaya-Putra is establishing a multidisciplinary research group in the Department of Aerospace and Mechanical Engineering to study the interface between engineering and medicine by leveraging stem cell and molecular therapies to model and treat diseases.

Research projects in his group include targeted drug delivery, stem cell engineering, and biomaterials to control stem cell morphogenesis into blood and lymphatic vasculatures.

Maria Holland is the Clare Boothe Luce Assistant Professor of Aerospace and Mechanical Engineering; she joined the University in 2017. Holland is a graduate of the University of Tulsa and also studied at Xiamen University in China. She earned her Ph.D. from Stanford University, which included time at Tsinghua University funded by the National Science Foundation.

Her work focuses on computational models of tissue growth and how the accompanying forces shape and influence tissue growth. She is currently focused on gyrification, the developmental process by which brains develop their characteristic fissures and folds.

Through theory, simulations, and analysis of medical images, she plans to explore this process in health and disease.

Sangpil Yoon joined the Notre Dame faculty this fall. In addition to his work in the Bioengineering Graduate Program, he serves as an assistant professor in the Department of Aerospace and Mechanical Engineering. Yoon completed his Ph.D. at the University of Texas at Austin and most recently served as a research associate in the Department of Biomedical Engineering at the University of Southern California, which was funded by a K99 fellowship.

Yoon’s interests are in biomedical applications of acoustics, and his lab utilizes ultrasonic transducers and microfluidic chips to develop integrated devices to engineer cells for patient-specific therapy. He has developed a novel method for transfecting cells with small molecules using acoustic waves.

Funding agencies:

1 National Science Foundation GRF

NIH, NSF, American Heart Association, ARMI, Craig H. Neilsen Foundation, DARPA, Juvenile Diabetes Research Foundation, Kelly Cares Foundation, Walther Cancer Foundation

2 Fulbright Fellowships 1 China Scholarship Council Fellowship 1 Science Foundation Ireland Visiting Fellowship

Commercialization:

2 Whitaker Fellowships

10 pending and awarded patents since 2007 1st Source Commercialization Award (Prof. Chang) 5 Countries

Commercialization and corporate partners:

10 Women

21 Students

Cubed Laboratories, Happe Spine LLC, IBM, Johnson & Johnson, Mars Bioimaging, Merck, Spinesmith LLC

11 Men

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3 Engineering Departments 11 Laboratories

Student Spotlights Bradley Ellis received his B.S. in 2015 from the University of Pittsburgh, where his undergraduate research focused on ascertaining the role of microvascular pericytes in ascending aortic disease. He spent his first year in the Notre Dame Bioengineering Graduate Program as a Naughton Fellow.

The Naughton Fellowship supports graduate students working on collaborative projects between Notre Dame and Irish universities. Ellis’ fellowship afforded him the opportunity to work on a collaborative project with Professor Abhay Pandit, director for the Centre for Research in Medical Devices at the National University of Ireland in Galway and a world-renowned biomaterials and biomedical engineering researcher, and Associate Professor Pinar Zorlutuna at Notre Dame. Ellis’ work during the Fellowship focused on utilizing stem cell-derived heart cells to better understand the role glycans have on cardiovascular regeneration in the context of cardiovascular disease.

inflammation during and after heart attacks through a model that mimics in vivo conditions. “I came to Notre Dame due to my interest in Professor Zorlutuna’s work on cardiovascular disease and because of the opportunities Notre Dame offers for collaborations with leaders in the biomedical field throughout the world,” Ellis said. Upon completion of his Ph.D., Ellis plans on staying in academia and hopes to one day head his own lab.

He currently works in the Zorlutuna lab designing and implementing microfluidic devices to study the effect of

to participate in University-driven research with clear translational potential was the primary reason why I was excited to attend Notre Dame. I gathered that the Notre Dame Bioengineering Graduate Program would be a unique graduate experience for me given the strong interdisciplinary influences and my advisor’s expertise, which both stem from traditional engineering departments,” she says.

The flexibility provided by additive manufacturing will be a pivotal tool in the investigation of novel materials for bearing surfaces. Characterization of material solutions processed with layer-wise forming processes has critical implications for instrument and device reliability.

Collaboration and fiscal partnership with DePuy Synthes, a Johnson & Johnson subsidiary, presents an exciting opportunity for Schiltz’s project to interface with industry and to contribute in the expansion of product offerings to better serve patients. “Currently, I am considering positions that support implementation of additive manufacturing on the path to eventually become a liaison between economics and scientific research in the industry,” says Schiltz.

Jessica Schiltz, a third-year Ph.D. student and a National Science Foundation Graduate Research Fellow, completed her undergraduate studies in biomedical engineering at Arizona State University. At Notre Dame she is studying the tribological properties of additively manufactured materials with applications to orthopaedics under the guidance of Professor Steven Schmid. “The opportunity

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Alumni Spotlights Ryan Ross, assistant professor in the Department of Cell & Molecular Medicine at Rush University Medical Center, considers Chicago his adopted hometown. But it wasn’t that long ago when he lived in South Bend and was part of the Bioengineering Graduate Program here on campus.

As a graduate student, his primary responsibilities were as a member of Professor Ryan Roeder’s research group, where he developed and tested gold nanoparticle-based X-ray contrast agents for the targeted detection of microdamage in bone tissue. He was also part of the larger group of bioengineering graduate students and faculty and helped organize weekly seminar series for the graduate students and faculty working in the Multidisciplinary Research Building. Upon receiving his doctorate from the University in 2011, he joined Rush as a postdoctoral fellow and instructor. In 2012, he was appointed research coordinator of the micro-computed tomography core

A native of Dundalk, Md., Thomas A. Metzger joined The Johns Hopkins Applied Physics Laboratory in Laurel, Md., in 2016 after receiving his doctorate in bioengineering from the University of Notre Dame. He serves as the section supervisor in the Human Computational Modeling Section of the Human Performance and Biomechanics Group. Metzger’s work focuses on understanding human biomechanics, specifically injury science, human dynamics and modeling, and warfighter protection. During his time as a graduate student at Notre Dame, he was a member of the Tissue Mechanics Laboratory, which is led by Professor Glen L. Niebur. Metzger also received a Fulbright Scholarship and Whitaker International Fellowship to study abroad at the National University of Ireland Galway.

“My time in Ireland was a life-changing experience. I was able to immerse myself in Irish culture and expand my technical

facility, a position he still holds, providing training, offering experimental design assistance, maintaining instruments, and managing the core billing. In 2016, he was promoted to assistant professor. His research focuses on bone diseases, such as osteoporosis, including their interactions with other diseases of aging, such as cognitive impairment. In addition to his duties at Rush, Ross is an active member of the Orthopaedic Research Society and the American Society for Bone and Mineral Research.

“I chose chemical engineering as an undergraduate at the University of California at Riverside because it allowed me to combine several of my interests into a single major,” he explains. “But I decided to pursue bioengineering at Notre Dame due to a particular interest in working on applied solutions to healthcare issues.” Ross stresses that the five years he spent working closely with Professor Roeder strengthened his choice and provided him with a clearer understanding of what a career in academic research entailed. “Without that training and mentorship, I would not be where I am now.”

skills to include cell culture, immunohistochemistry, and confocal microscopy,” he says. In addition to technical skills, Metzger developed his early mentorship skills while at Notre Dame. He worked closely with two undergraduate students, one of whom went on to earn a Ph.D. at the Georgia Institute of Technology and another who will be entering medical school next year.

Metzger served as a volunteer at the St. Vincent DePaul food shelter, and he took advantage of the opportunities Notre Dame students have to participate in intramural sports.

He says, “I chose engineering because of a lifelong passion for critical thinking and problem solving. My time as an undergraduate at the University of Maryland and as a graduate student at the University of Notre Dame not only helped me hone my technical skills but also provided a number of opportunities to grow in leadership. The communication and teamwork skills I learned and refined during my time at Notre Dame continue to be used at the Johns Hopkins Applied Physics Laboratory.”

Alumni news spotlights We love to hear from our alumni. Please send information about new positions, honors, awards, and more to Professor Glen Niebur at gniebur@nd.edu.

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Bioengineering Graduate Program University of Notre Dame 153 Multidisciplinary Research Building Notre Dame, IN 46556-4634 bme.nd.edu

Participating Faculty Biomaterials Donny Hanjaya-Putra Maria Holland Ryan Roeder Tim Ovaert Joshua Shrout Matthew Webber

Cancer Sharon Stack Sangpil Yoon

Computational and Systems Biology Greg Madey Tijana Milenkovic

Drug Delivery/Therapeutics Basar Bilgicer Hsueh Chia Chang Donny Hanjaya-Putra Ryan Roeder Matthew Webber Sangpil Yoon

Environmental Science Joshua Shrout Robert Nerenburg

Genomics, DNA, RNA Gregory Timp

Health Robotics and Technology James Schmiedeler Patrick Wensing

Imaging Paul Bohn Danny Chen Scott Howard Thomas O’Sullivan Ryan Roeder Bradley Smith Sangpil Yoon

Mechanobiology and Physical Effects on Cells Donny Hanjaya-Putra Maria Holland Glen Niebur Sangpil Yoon Pinar Zorlutuna

Orthopaedics Glen Niebur Tim Ovaert Matt Ravosa Ryan Roeder Steven Schmid Joshua Shrout

Regenerative Medicine Donny Hanjaya-Putra Glen Niebur Gregory Timp Matthew Webber Sangpil Yoon Jeremiah Zartman Pinar Zorlutuna

Rehabilitation and Motor Control James Schmiedeler Patrick Wensing

Sensors and Diagnostics Basar Bilgicer Paul Bohn Hsueh Chia Chang David Go Joshua Shrout Thomas O’Sullivan Bradley Smith Sangpil Yoon