Fall 2022 Magazine | Wallace H. Coulter Department of Biomedical Engineering

FALL 2022 MAGAZINE

MEET OUR NEW CHAIR

Creativity's Spark Building on RADx A BREATH OF HOPE

COULTER BME AT A GLANCE

Coulter BME by the Numbers #2 #1 1,162 377

#2

undergraduate BME program in the nation U.S. News & World Report, 2023 Best Colleges

… in the nation in BME degrees awarded to women … in the nation in BME degrees awarded to students from underrepresented backgrounds

undergrad students

graduate students

59% women

50% women

graduate BME program in the nation U.S. News & World Report, 2023 Best Colleges

$41M

50+

Annual Research Awards (FY22)

25%

underrepresented minorities

27%

underrepresented minorities

Patents issued to faculty since 2015

nearly

3/4

of BME undergrads engage in research

After graduating,

51% of BME PhDs go into academia 42% take industry or government positions

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Wallace H. Coulter Department of Biomedical Engineering

COULTER BME AT A GLANCE

Degree Programs

Leadership

B.S. in Biomedical Engineering Georgia Tech

ALYSSA PANITCH Wallace H. Coulter Department Chair

M.S. in Biomedical Engineering Georgia Tech

ESSY BEHRAVESH Director of Student Services

Master of Biomedical Innovation and Development Georgia Tech

PAUL J. BENKESER Senior Associate Chair

M.S. in Biomedical Innovation and Development – Advanced Therapeutics Emory University coming soon Ph.D. in Biomedical Engineering Emory University & Georgia Tech Ph.D. in Biomedical Engineering Emory University, Georgia Tech, & Peking University M.D. / Ph.D. Emory University & Georgia Tech Interdisciplinary Ph.D. programs Georgia Tech • • • • •

Bioengineering Bioinformatics Computational Science and Engineering Machine Learning Robotics

LAKSHMI “PRASAD” DASI Associate Chair for Undergraduate Studies SCOTT HOLLISTER Associate Chair for Translational Research HANJOONG JO Associate Chair for Emory JOE LE DOUX Executive Director of Training and Learning MACHELLE T. PARDUE Associate Chair for Faculty Development Interim Department Chair 2021-22 MANU PLATT Associate Chair for Graduate Studies CHENG ZHU Executive Director for International Programs LUKE O’CONNELL Director of Development, Georgia Tech SHAWN STERN Director of Development, Emory

The Wallace H. Coulter Department of Biomedical Engineering (Coulter BME) is a true success story in risk-taking and innovation — a visionary partnership between a leading public engineering school and a highly respected private medical school.

Fall 2022 Magazine

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FROM THE CHAIR

T

he fall semester is in its early weeks as you read this, and I so enjoy the fresh starts and new opportunities the beginning of an academic year heralds.

Our campuses are just brimming with possibility and energy. This fall marks a beginning for me, too, as the new leader of the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University. I joined the Coulter BME family this summer, and I am grateful for and humbled by the opportunity to lead this unique, powerful Department.

I am still very much in a phase of listening and learning, but I can confidently tell you that the students, staff, and faculty in our Department are every bit as impressive as our reputation suggests.

In these pages, I am pleased to share a small window into their work, as well as a deeper conversation about my work and my early thoughts on the opportunities for us. You’ll meet students who have turned ideas and projects into real-world solutions for surgeons, physical therapists, patients with spinal cord injuries, and much more. Some of these innovations have ended up in academic journals, and others are serving their fellow undergraduates by filling a need on campus.

Other stories detail new advances in a powerful cancer treatment using CAR T cells and in understanding a mostly untreatable form of prostate cancer. Researchers in neuroengineering are devising a potentially revolutionary new kind of universal brain-machine interface that uses artificial intelligence to decode brain signals in real-time. They are finding new connections between cognition and balance and new ways to understand the brain using AI (then using that understanding to inspire designs for artificial neural networks). A powerful partnership between two of our researchers is unlocking the potential of mRNA therapies and finding the most effective ways to get them to target cells. Our teams are advancing soft robotics, 3D imaging of live cells, understanding of aging, and so much more.

What I see in our magazine — and what I hope you will, too — is an impactful, energetic organization. I’m thrilled to be part of the 25-year story of Coulter BME and to work with our entire community to build the next phase of our journey.

Just over the horizon, for example, we have exciting developments, including the new Health Sciences Research Building II at Emory and a forthcoming Emory master’s degree in advanced therapeutics.

All that we do is the result of partnership; it is the core of our Department. It’s my honor to be the newest partner alongside our staff, faculty, students, alumni, friends, colleagues around the world — and you. Thank you for continued support and for helping us share our message.

Warmly, Alyssa Panitch, Ph.D. Wallace H. Coulter Department Chair Professor

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Wallace H. Coulter Department of Biomedical Engineering

TABLE OF CONTENTS

Inside COULTER BME FALL 2022 MAGAZINE FEATURES

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Our Next Chapter A conversation with new Chair Alyssa Panitch

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Creativity's Spark From surgical tools to virtual medicine, student innovators are leading the way on improving lives

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A Breath of Hope Custom 3D-printed airway splint is giving one little girl a chance at life

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Building on the RADx Experience What’s next for the research team credited with the wide availability of at-home Covid tests

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DEPARTMENTS 5

Our Research

43

Our Community

61

Biolocity

25

37

Fall 2022 Magazine

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Our RESEARCH Biomaterials and Regenerative Technologies • Biomedical Imaging and Instrumentation Biomedical Informatics and Systems Modeling • Biomedical Robotics Cancer Technologies • Cardiovascular Engineering • Engineering Education Immunoengineering • Neuroengineering

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Wallace H. Coulter Department of Biomedical Engineering

OUR RESEARCH

Heat-Controllable CAR T Cells Destroy Tumors, Prevent Relapse CAR T-cell therapy has emerged as a viable cure for some cancers. Now bioengineers are expanding the precision and effectiveness of this revolutionary immunotherapy, which involves engineering a patient’s T cells in a lab. Then a chimeric antigen receptor (CAR) is added, and these customized immune cells are returned to the patient’s body, where they seek and destroy cancer cells.

That’s how it works, when it works.

“These therapies have proven remarkably effective for patients with liquid tumors — so, tumors that are circulating in the blood, such as leukemia,” said Gabe Kwong, associate professor in Coulter BME. “Unfortunately, for solid tumors — sarcomas, carcinomas — they don’t work well. There are many different reasons why. One huge problem is that the CAR T cells are immunosuppressed by the tumor microenvironment.”

To enhance the way CAR T cells fight cancer, Kwong and his collaborators are changing that microenvironment and making some cell modifications of their own. They’ve added a genetic on-off switch to the cells and developed a remote-control system that sends the modified T cells on a precision invasion of the tumor microenvironment, where they kill the tumor and prevent a relapse. They explained it all in the journal Nature Biomedical Engineering.

The latest study builds on the lab’s body of work exploring remotely

Gabe Kwong (standing) and Ph.D. student Ali Zamat added a genetic on-off switch to CAR T cells and developed a heat-activation system to enhance how the cells attack tumors. (PHOTO: JERRY GRILLO)

controlled cell therapies. Researchers can precisely target tumors, wherever they are in the body, with a local deposition of heat. “This heat basically activates the CAR T cells inside the tumors, overcoming the problems of immunosuppression,” Kwong said.

The real novelty, Kwong said, was in genetically engineering clinical-grade CAR T cells, something the team worked on for the past three years. Now, in addition to a switch that responds to heat, the researchers have added a few upgrades to the T cells, rewiring them to produce engineered proteins to stimulate the immune system.

“These cancer-fighting proteins are really good at stimulating CAR T cells,

but they are too toxic to be used outside of tumors,” Kwong said. “They are too toxic to be delivered systemically. But with our approach we can localize these proteins safely. We get all the benefits without the drawbacks.”

The latest study shows the system cured cancer in mice, shrinking tumors and preventing relapse — critical for long-term survival. Further studies will delve into additional tailoring of T cells, as well as how heat will be deposited at the tumor site for human studies.

“We’ll use focused ultrasound, which is completely noninvasive and can target any site in the body,” Kwong said. ‣ JERRY GRILLO

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OUR RESEARCH

Standardizing Spheroid Data to Solve the Reproducibility Puzzle A key part of scientific research is the ability for other scientists or labs to recreate the results produced by a research team.

For powerful Takayama 3D cellular models called spheroids, that hasn’t always been the case. There’s just been too much variability in how each research team grows and uses the cells.

A globe-spanning consortium of labs is hoping to change that with a new database cataloging the details of more than 3,000 experiments involving these spheroid models, creating a resource with standardized details that could help other teams reproduce

experiments and achieve the same results. Their work was published in November in the journal Nature Methods.

“This paper is partly a call to the research community to help solve this puzzle of reproducibility by having everyone contribute information so people can think about it and analyze it,” said Shuichi Takayama, professor and Price Gilbert Jr. Chair in the Coulter Department.

Spheroids are three-dimensional cell cultures that form nearly spherical shapes. They’re often better at mimicking how cells behave in the body than traditional cell cultures in a dish since they more accurately reflect cells’ arrangement in all three dimensions.

The 3D cell models are powerful tools for studying disease mechanisms or testing cell responses to potential drugs.

But the field is relatively young, and there is no one-size-fits-all approach to experiments using spheroids. Without

detailed data about experimental setups, and even how the cell cultures were grown in the first place, results are difficult to analyze or reproduce.

“There are myriad factors that can affect experiments — how long you grow cells, how new they are. The cells that you grow in an incubator on day one could be different than how they are on day 30,” said Ph.D. student Tasdiq Ahmed, a member of the research team. “The paper includes a meta-analysis of every breast cancer spheroid paper there is, and it’s kind of shocking how many papers don’t report a lot of experimental parameters.”

In developing the new knowledgebase, the researchers aim to fill those gaps.

They settled on four key pieces of data to include about each spheroid experiment.

Their ultimate goal is to establish minimum information guidelines like those for experiments in other biological and biomedical fields. ‣ JOSHUA STEWART

Probing ‘Zombie’ Cells to Understand the Aging Process Sometimes, cells permanently stop dividing but remain active — you could say they are undead. Scientists have appropriately nicknamed them “zombie” cells, which is a much more colorful description than the biological term, senescence.

Resistant to the natural process of cell death, or apoptosis, they no longer contribute to tissue repair or homeostasis and instead are known to release harmful substances, causing inflammation and damage to cells nearby and in distant organs.

So-called zombie cells increase as we age, and they are thought to be a central cause of age-related diseases and frailty. That’s why Denis Tsygankov and his collaborators are trying to dig up the underlying workings of senescence with the help of a new two-year National Institutes of Health grant.

“This project will build the first mathematical model to characterize senescence in the entire human organism, unveiling its regulation and dynamics, and its role in the physiological or pathological processes during human aging,” said

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Tsygankov, an expert in computational biology and mathematical modeling.

With collaborators at the University of North Carolina, Tsygankov’s project focuses on a central biomarker of senescence called p16, which has been identified as a trustworthy biomarker of aging.

“Our top goal in this project is to develop quantitative, mechanistic models of p16 dynamics at the cellular and whole organism scales, and determine if the p16 measured in T cells actually reflects the overall senescence load at the systems level,” Tysgankov said.

The team is working under the broad theme that aging may not be reversed, but it can be slowed down. A quantitative understanding of p16’s role as a biomarker of senescence, and the ability to control it, could guide clinical decisions and improve health care.

“Treatment plans such as chemotherapy can be dependent on a patient’s age,” Tsygankov said. “But chronological age and molecular or biological age are different things. We all age differently.” ‣ JERRY GRILLO

Wallace H. Coulter Department of Biomedical Engineering

Tsygankov

Study Links Poor Cognitive Focus Shifting to Poor Balance Recovery, Even in Healthy Adults Researchers at Emory University and Georgia Tech have documented a connection between a higher-level brain function and balance control that may one day offer an early warning for older adults that they’re at risk of developing balance problems or falling down.

In essence, healthy adults with stiffer cognitive behaviors also have stiffer motor behaviors, as lead author and former Ph.D. student Aiden Payne has described it. Led by Lina Ting, the team published their findings in the journal Frontiers in Aging Neuroscience. Ting said the study subjects had no clinically diagnosed balance disorders, and the connection holds even accounting for natural differences in cognitive and balance capability between individuals. “[This relationship] may be a way to kind of have an early indicator of people who may be at risk for falls but wouldn't get picked up on any type of clinical test,” said Ting, McCamish Foundation Distinguished Chair in Coulter BME. “So, if we want to do healthy aging and prevention of falling, then now would be the time to intervene to help these people maintain their faculties.”

Ting said people typically aren’t diagnosed with balance disorders until they’ve already fallen. Earlier warnings could allow time for interventions like exercise to help people maintain their motor and cognitive function.

In the study, the team tested individuals’ cognitive set-shifting skills, an executive function of the brain that allows us to change behavior between contexts. Then they put subjects on a moving platform and disrupted their balance.

They found people with poorer set-shifting ability also responded more aggressively to the loss of balance.

Above: Researchers in Lena Ting’s lab use this shifting floor to study balance and brain activity. Inset: Lena Ting.

(PHOTOS: ROB FELT)

“This may be a way to kind of have an early indicator of people who may be at risk for falls but wouldn't get picked up on any type of clinical test.”

— LENA TING

Instead of only activating specific muscles to counter the platform’s shift and restore balance, these people activated opposing muscle groups, and their brain activity was more pronounced than those with better set-shifting skills.

“Their muscle activity is less specific; they're not responding in a way that's specific to the task,” Ting said. With lots of muscles moving, including groups that counteract each other, the participants

stiffened their body overall instead of reacting only to the direction of the movement.

“They're doing this behavior that helps them not have to guess or not have to actually figure out what's going on,” Ting said, “but ultimately, it's not good for your balance.”

In other words, their brains struggled to shift contexts with motor functions just as they showed reduced ability to shift contexts in thinking tasks.

Scientists have long observed a connection between declining cognitive function and an increased risk of falling down, though the specifics of the link remain foggy. Ting’s lab has published previous papers showing that impaired set shifting is associated with how frequently people have fallen in the past, but this is the first time they’ve linked it to the potential for balance problems.

‣ JOSHUA STEWART

Fall 2022 Magazine

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OUR RESEARCH

Artificial Intelligence Could Unlock Faster, Universal Brain-Machine Interfaces for Paralyzed Patients The seemingly simple act of reaching for a cup isn’t really simple at all. In truth, our brains issue hundreds, maybe thousands of instructions to make that happen: positioning your body just right, maybe leaning forward a bit, actually lifting your arm and reaching out, grasping the cup with your fingers, and a whole host of tiny movements and adjustments along the way.

Scientists can record all of the neural activity related to the movement, but it’s complicated and messy. “Seemingly random and noisy,” is the way Assistant Professor Chethan Pandarinath describes it. So how do you pick out the signal from the noise, to identify the activity that controls all those movements and says to the body, “pick up the cup”?

Pandarinath thinks he has a way, using new artificial intelligence tools and our growing understanding of neuroscience at a system-wide level. It’s an approach he’s been building toward for years, and he’s after a goal that could be nothing short of revolutionary: creating brain-machine interfaces that can decode in just milliseconds, and with unprecedented accuracy, what the brain is telling the body to do. The hope is to reconnect the brain and the body for patients who are paralyzed from strokes, spinal cord injuries, or ALS — amyotrophic lateral sclerosis, or Lou Gehrig’s disease.

The National Institutes of Health has recognized the creativity of Pandarinath’s approach — and its transformative potential — with a 2021 Director’s New Innovator Award, the agency’s most prestigious program for early career researchers. With that support, the team — including Emory neurosurgeons Nicholas Au Yong and Robert Gross and neurologist Jonathan Glass, who’s also director of the Emory ALS Center — has launched a multi-site clinical trial with ALS patients.

“To move this toward a clinical trial, that really is a collaboration between BME and Neurosurgery and Neurology. That's pretty exciting.

That's the only way we can make clinical impact,” Pandarinath said.

Ideally, the AI-powered brain-machine interfaces Pandarinath proposes

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Pandarinath (PHOTO: JACK KEARSE)

Pandarinath is after a goal that could be nothing short of revolutionary: creating brain-machine interfaces that can decode in just milliseconds, and with unprecedented accuracy, what the brain is telling the body to do.

would work almost “out of the box” for any patient, without significant calibration. His team’s approach hinges on a concept in machine learning called “unsupervised” or “self-supervised” learning. Rather than starting with a movement and trying to map it to specific brain activity, Pandarinath’s algorithms start with the brain data.

“We don't worry about what the person was trying to do. If we just focus on that, we're going to miss a lot of the structure of the activity. If we can just understand the data better first, without biasing it by what we think the pattern meant, it ends up leading to better what we call ‘decoding,’” he said.

These artificial intelligence tools have

Wallace H. Coulter Department of Biomedical Engineering

been reshaping other fields — for example, computer vision for autonomous vehicles, where AI has to understand the surrounding environment, or teaching computers to play chess or complicated video games. Pandarinath has been working to apply unsupervised learning techniques to neuroscience and uncover what the brain is doing.

“That's not something that other people have done before — at least not like what we're doing. That's kind of our secret sauce,” he said. “We know these tools are changing the game in so many other AI applications. We're showing how they can apply in brain-machine interfaces and impact people's health.”

‣ JOSHUA STEWART

OUR RESEARCH

Tracing Neural Circuits to Chemotherapy's Constellation of Side Effects Severe and persistent disability often undermines the life-saving benefits of cancer treatment. Pain and fatigue — together with sensory, motor, and cognitive disorders — are chief among the side effects that occur with the platinum-based agents used widely in chemotherapy treatments.

A study by researchers in the lab of Coulter BME’s Timothy C. Cope has found a novel pathway for understanding why these debilitating conditions happen for cancer patients and why scientists should focus on all of the possible neural processes that deliver sensory or motor problems to a patient’s brain — including the central nervous system — and not just the “peripheral degeneration of sensory neurons” that occurs away from the center of the body.

The findings are published in the Proceedings of the National Academy of Sciences and could impact development of effective treatments that are not yet available for restoring a patient’s normal abilities to receive and process sensory input as part of post cancer treatment, in particular.

“Chemotherapy undoubtedly negatively influences the peripheral nervous

system, which is often viewed as the main culprit of neurologic disorders during cancer treatment,” said Stephen N. (Nick) Housley, a postdoctoral researcher in the School of Biological Sciences and the lead author. However, he said, for the nervous system to operate normally, both the peripheral and central nervous system must cooperate.

“This occurs through synaptic communication between neurons. Through an elegant series of studies, we show that those hubs of communication in the central nervous system are also vulnerable to cancer treatment’s adverse effects,” Housley said. He added that the findings force “recognition of the numerous places throughout the nervous system that we have to treat if we ever want to fix the neurological consequences of cancer treatment — because correcting

Cope

Housley

any one may not be enough to improve human function and quality of life.”

“These disabilities remain clinically unmitigated and empirically unexplained as research concentrates on peripheral degeneration of sensory neurons,” the research team explained in the study, “while understating the possible involvement of neural processes within the central nervous system. The present findings demonstrate functional defects in the fundamental properties of information processing localized within the central nervous system.

“Long-lasting sensorimotor and possibly other disabilities induced by cancer treatment result from independent neural defects compounded across both peripheral and central nervous systems.” ‣ RENAY SAN MIGUEL

“The findings force recognition of the numerous places throughout the nervous system that we have to treat if we ever want to fix the neurological consequences of cancer treatment — because correcting any one may not be enough to improve human function and quality of life.”

— NICK HOUSLEY

Fall 2022 Magazine

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OUR RESEARCH

Prostate Cancer Organoids Open Path to Precision Oncology Androgen receptor pathway inhibitors can prolong survival for patients with advanced prostate cancer. But about 20% of patients develop more advanced-stage neuroendocrine prostate cancer in response to this type of hormone therapy, and so far, researchers haven’t had effective ways to study that progression.

“These patients lose their dependency on hormone-driven processes, and conventional treatments don’t work for them,” said Coulter BME Associate Professor Ankur Singh.

“There are no targeted therapies, so there is a clear clinical need.”

No models exist to effectively study this kind of cancer — a major challenge.

That’s why Singh and a multi-institution team developed a prostate cancer organoid that can model the patientspecific microenvironment. It could offer an important step forward in precision medicine. They described the work in the journal Advanced Materials.

Organoids are tiny, three-dimensional tissue cultures grown from a patient’s cells. They can be engineered to replicate different organs of the human body or to model diseases. Produced entirely in vitro, organoids are valuable tools for researchers, who can explore targeted treatments in authentic human microanatomies without harming a patient.

Scientists grow organoids in a gel that acts as the extracellular matrix — the protein-rich molecular network that surrounds and supports cells in the body, helping them attach to and communicate with one another and playing a key role in multiple cell functions.

Singh’s collaborators on this study had previously developed organoid models of neuroendocrine prostate cancer grown in Matrigel, a naturally derived solution from mouse tumor cells. Using these organoids, the researchers had discovered a new therapeutic target called EZH2, a histone-modifying protein that promotes tumor growth.

Using an EZH2 inhibitor, they were able to slow tumor growth but not always eliminate the tumors altogether.

Reasoning that the EZH2 inhibitor would reach full potential in the right kind of tumor microenvironment, they analyzed 111 patient biopsies using a multi-omics approach and microscopy techniques to thoroughly profile these aggressive tumors.

Their findings helped them design and develop a synthetic hydrogel that accurately mimics the extracellular matrix of a patient-specific tumor.

Using these organoids, the researchers were able to study the impact of the matrix on tumor development — particularly the changes associated with transforming a treatable prostate cancer tumor into an untreatable one.

With the new organoids, they discovered that extracellular matrix regulates EZH2 activity and the efficacy

Singh (PHOTO: JERRY GRILLO)

of EZH2 inhibitors, a previously less understood phenomenon. They also discovered a potential new therapeutic target, a molecule called DRD2.

Currently, DRD2 inhibitors are being tested in clinical trials for gliomas, but they have never been tested in neuroendocrine prostate tumors.

Singh’s team found that certain extracellular matrices found in patients could render neuroendocrine tumors resistant to DRD2 inhibitors, but the resistance could be overcome with a combination therapy: first, an EZH2 inhibitor to reprogram the cells and make them more susceptible to a follow-up DRD2 inhibitor.

“Not every patient’s tumor microenvironment is the same,” Singh said. “We could take a biopsy sample, profile the patient’s microenvironment, take that specific information and create an organoid model that you can treat with drugs and develop a personalized treatment regime. Tailoring this towards precision oncology would be pretty huge for us. That is the ultimate goal.” ‣ JERRY GRILLO

Two organoids: A Matrigel-based organoid is at top. Ankur Singh's team developed a new, improved synthetic hydrogel organoid (bottom) as a prostate cancer model. (PHOTOS COURTESY: ANKUR SINGH) 11

Wallace H. Coulter Department of Biomedical Engineering

OUR RESEARCH

Flowing Toward a Potential Atherosclerosis Therapeutic It’s not a blockbuster cardiovascular drug — yet. But the pathway from bench to bedside is easy to see.

In a January eLife paper, Hanjoong Jo’s lab characterizes a “flow-kine”: a protein produced by endothelial cells in response to healthy blood flow patterns.

Unlike other atherosclerosis-linked factors previously identified by Jo’s team, this one — called KLK10 — is secreted. That means that the KLK10 protein could morph into a therapeutic.

KLK10 can be compared to PCSK9 inhibitors, which lower LDL cholesterol and have a proven ability to prevent cardiovascular events. KLK10 acts in a different way, not affecting cholesterol, but instead inhibiting inflammation in endothelial cells, and it can protect against atherosclerosis in animal models when delivered by injection.

“The most important clinical implication is that we were able to see that human atherosclerotic plaques have a low level of KLK10,” said Jo,

Wallace H. Coulter Distinguished Faculty Chair. “In a healthy heart, the expression level is OK.” Jo sees similarities between KLK10 and myokines, exercise-induced proteins secreted by skeletal muscle cells. Looking ahead, his lab has begun experiments testing how exercise affects KLK10 and other protective factors.

Using a workhorse model of disturbed blood flow in atherosclerosis, Jo’s team has steadily identified a stream of genes involved in the disease process. KLK10 is one of several downregulated by disturbed blood flow.

Jo cites the transcription factor KLF2 as another good example of a protective protein identified by his team’s approach.

KLF2 has a similar protective function, but it is expressed inside endothelial cells and stays inside the cell. KLK10 is secreted into the circulation, giving it more obvious therapeutic potential.

Exactly how KLK10 works in the context of cardiovascular health is still

Helmsley Trust Supports Qiu’s Long-Term Crohn’s Disease Study Crohn’s disease can affect any part of the gastrointestinal tract, its severity waxing and waning through the years.

The precise cause of this devastating inflammatory bowel disease is still unknown. A Crohn’s diagnosis means a lifetime of treatment — drugs can stabilize the disease, helping to regulate an overactive immune system. But for some patients, Crohn’s disease will continue on its destructive path, causing progressive damage.

“That’s because the disease location and behavior can vary over time for each person,” said Peng Qiu, associate professor in Coulter BME. “Yet most research in Crohn’s disease is still being carried out by investigating one single biopsy from a single time point.”

This snapshot-in-time approach just isn’t cutting it. So Qiu is Qiu leading a team of researchers on a deeper dive into the assessment and tracking of Crohn’s with a $2.8 million grant from The Leona M. and Harry B. Helmsley Charitable Trust.

With collaborators Subra Kugathasan at Emory and Children’s Healthcare of Atlanta and Greg Gibson in Georgia Tech’s School of Biological Sciences, Qiu wants to expand Crohn’s research beyond that single time point. The team is working under the hypothesis that an evaluation of 50 newly diagnosed pediatric patients

Jo

unclear. Since it is a serine protease — an enzyme that snips other proteins — we might assume that its job is to cut something. But preliminary experiments suggest that KLK10 is instead binding another protein to regulate inflammation. Jo is eager to publish more on that story next. ‣ QUINN EASTMAN

who have never undergone treatment for their illness, across several time points, will lead to a fuller picture of the Crohn’s disease landscape.

They plan a quantitative analysis of each patient, generating single-cell RNA-sequencing data — first, to set a baseline at initial diagnosis, then again once or twice over three years.

They’ll also compare the baseline data with down-the-road treatment outcomes, searching for specialized cell populations and gene expression signals that can predict how a patient responds to treatment.

“Longitudinal studies at such a single-cell level will provide deeper understanding and lead to new ideas for disease prevention and treatments,” Qiu said. “If we’re successful, those cell populations and genes will be useful for developing hypotheses for personalized treatment, and ultimately, improving patients’ qualify of life.” ‣ JERRY GRILLO

Fall 2022 Magazine

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Eva Dyer is an emerging leader in the growing field of computational neuroscience. (PHOTO: GARY MEEK)

Using AI to Understand the Brain — and the Brain to Build Better AI When someone asks Assistant Professor Eva Dyer what she does for a living, she has a short and simple answer: “I try to teach machines how to understand the brain.”

As the principal investigator of the Neural Data Science Lab — or NerDS Lab — she leads a diverse team of researchers in developing machine learning approaches to analyze and interpret massive, complex neural datasets. At the same time, they are designing better machines, inspired by the organization and function of biological brains.

In other words, they’re moving knowledge back and forth, from machine learning to neuroscience and from neuroscience to machine learning, and their work is drawing national attention, acclaim, and support.

In the summer of 2020, Dyer was one of three researchers in the U.S. to secure a McKnight Technological Innovations in Neuroscience Award.

Then she won a BRAIN Award — Brain Research through Advancing Innovative Neurotechnologies — from the National Institutes of Health (NIH). She’s also been busy publishing and presenting work at major conferences, including NeurIPS in late 2021, the conference on Neural Information Processing Systems.

The work her lab presented — about 13

a new set of tools in self-supervised learning, a method of machine learning that more closely imitates how humans classify objects — is the team’s latest contribution in addressing one of the biggest challenges in neuroscience: finding simplified representations of neural activity that allow for greater insights into the link between the brain and behavior.

As neural datasets continue to grow in size and complexity, Dyer’s work is driving scientific understanding of the brain. Calling herself a computational neuroscientist, Dyer blends multiple disciplines, including electrical engineering, computer science, and physics, using mathematical tools and theories to understand how brains process information. That’s the simple version. Probing a single neuronal circuit means probing a collection of hundreds of thousands of neurons of many different cell types, because brains are heterogenous.

“An active area of research in my lab is trying to uncover the functional properties of individual cell types, to ultimately build AI systems of the future,” said Dyer, who envisions artificial neural networks that will more closely resemble the workings of biological brains. “We think that heterogeneity will have an important use in AI. But we still haven’t figured out what that is.”

Wallace H. Coulter Department of Biomedical Engineering

The main goal of her lab’s vigilance in studying all of that brain data, in comparing all of those numbers, is to figure out how the coordinated activity of large collections of neurons change in the presence of something like disease or addiction.

“We think these tools we’re developing will give us the ability to suss that out,” Dyer said.

Along the way, she also is considering the large environmental footprint of artificial intelligence, specifically the energy required to keep it all going. “AI and computation consume a lot of global energy right now; it’s a real problem.”

Unlike biological neurons, artificial neural networks are basically talking all of the time, wasting energy. It’s an area where she sees promise in her work translating the structure and behavior of the brain to artificial neural networks.

“Neurons in the brain only fire when they have something to say — they’re saying nothing, then they spike. It’s sort of a binary event,” Dyer said. “What if we build spiking neural networks, where artificial neurons only fire when they have to? That would be a way forward. We could create a next-generation, energyefficient computer infrastructure using brain-inspired principles.” ‣ JERRY GRILLO

OUR RESEARCH

Researchers Create ‘Biohybrid’ Fish Powered by Human Heart Cells To learn how to make an artificial heart, Harvard, Emory, and Georgia Tech researchers have made artificial fish.

The fish are made from human cardiac muscle cells, painstakingly grown on laboratory tape coated with gelatin. The “biohybrid” fish swim by recreating the muscle contractions of a pumping heart, bringing engineers closer to creating more complex artificial pumps and providing a platform to study human diseases, such as cardiac arrhythmias.

Biomedical engineer Sung Jin Park began working on biohybrid fish as a postdoc in Kit Parker’s lab at Harvard University. Park is co-first author of a paper in Science describing their approach.

“Our major achievement in this paper is that we can build a living muscle that can self-control and self-pace its movement without any additional control mechanism,” said Park, now an assistant professor in the Coulter Department.

Park said his team’s research could be applied to design “biological pacemakers,” a potential alternative to electronic cardiac pacemakers. As part of a long-term implant, biological pacemakers could grow along with a pediatric patient.

“Our ultimate goal is to build an artificial heart to replace a malformed heart in a child,” said Park, senior author of the Science paper. “Rather than using heart imaging as a blueprint, we are identifying the key biophysical principles that make the heart work, using them as design criteria, and replicating them in a system — a living, swimming fish — where it is much easier to see if we are successful.”

The fish has two layers of muscle cells, one on each side of the tail fin. When one side contracts, the other stretches.

The stretch triggers the opening of an ion channel sensitive to mechanical movement, leading to an influx of charged ions and a contraction on that side.

The researchers also engineered an “autonomous pacing node” to control the frequency and rhythm of the spontaneous contractions, acting like a pacemaker. Together, the two layers of muscle and the autonomous pacing node enable the generation of continuous, spontaneous, and coordinated, back-andforth fin movements. The system can propel the fish for more than 100 days.

The human cardiac muscle cells used in this research are commercially available. They come from induced pluripotent stem cells, which are originally derived from skin cells. ‣ QUINN EASTMAN

The research could be applied to design “biological pacemakers,” a potential alternative to electronic cardiac pacemakers. As part of a long-term implant, biological pacemakers could grow along with a pediatric patient.

PHOTO: MICHAEL ROSNACH, KEEL YONG LEE, SUNG-JIN PARK, KEVIN KIT PARKER

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OUR RESEARCH

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Jia Building Next-Gen 3D Imaging for Live Cells

Georgia Tech Selected as NIH Cell Characterization Hub

Biomedical engineer Shu Jia has been building a research program focused on advancing microscope technology and creating innovative approaches to imaging in biology, helping clinicians and researchers take better pictures of the cells and tissues they’re studying.

Now he’s taking the next big step. The Coulter Department assistant professor is building a next-generation platform for fluorescence microscopes that could reshape how we see live cells, capturing ultrafast 3D images of single cells. His new system would vastly improve the resolution of conventional microscopes, and it would amp up a technique called microfluidics imaging to achieve detailed and clear 3D images of cells in flow in one snapshot.

“You can bring any types of cells, any biological questions to this platform for imaging,” Jia said, “so it would have a broad impact.”

The National Science Foundation (NSF) agreed with the potential for Jia’s work to make a real difference in the search for answers to difficult questions in health and biology. He has received a Faculty Early Career Development Award from the agency, a five-year grant designed to help promising researchers establish a foundation for a lifetime of leadership in their field. Known as CAREER awards, the grants are NSF’s most prestigious funding for untenured assistant professors.

“This award is a very important step for our lab,” Jia said. “We work to build biophotonic tools at the systems level; that means we build hardware, software, algorithms, data science, and applications —

Krishnendu Roy will lead a new in-depth characterization platform hub for a National Institutes of Health program that aims to develop transformative therapies based on adult stem cells.

The University of Maryland, Baltimore is leading the cell-characterization activities under the Regenerative Medicine Innovation Project (RMIP) and selected Georgia Tech and Roy’s team. The hub will provide in-depth cell characterization of human adult source stem cells used in RMIP studies, as well as stem cell products that RMIP awardees develop for clinical application.

“Our analysis will provide researchers a deeper understanding of the cell products in these various clinical and pre-clinical trials — the characteristics that contribute to their safety and efficacy, for example,” said Roy, the Robert A. Milton Endowed Chair in Coulter BME. Through this kind of in-depth analysis of every cell therapy that is manufactured or used in an RMIP project, researchers will create what Roy and others call a “cell fingerprint.”

“When we have created a large enough database, scientists will be able to correlate the cell fingerprint with the outcomes of a particular disease in a particular patient and gain insights into the critical quality attributes of the cells that make them most effective for a specific patient,” Roy said. ‣ JERRY GRILLO

Jia

a whole pipeline. In the long term, we hope to establish and advance our leadership in this area, especially at the interface between imaging and the life sciences.”

Jia calls his advanced imaging platform “multiplexing light-field instrumentation and methods,” which speaks to his whole-pipeline approach to light-based biological imaging. The idea is to simplify and speed up how researchers and doctors study cells while limiting cell damage from extended exposure to light during the imaging process.

His proposed platform includes three modules: one uses an array of tiny lenses to collect reflected light and the angle of that light to reconstruct 3D images; the second would provide nanometers of resolution, far greater than currently possible for conventional microscopes; and the third advances microfluidics imaging, collecting 3D images of lots of individual cells in a single snapshot.

‣ JOSHUA STEWART

Wallace H. Coulter Department of Biomedical Engineering

Roy

New System Speeds Screening of Drug-Delivering Nanoparticles Long before the Covid-19 pandemic put a global spotlight on mRNA-based vaccines, two researchers in the Coulter Department were combining their distinct skillsets to leverage the clinical potential of mRNA. Some of their latest work could clear the way to making therapeutic discoveries even faster.

Therapeutics made from mRNA or DNA hold promise in addressing lots of diseases, but they have to be delivered to the right place in the body to work.

Several years ago, Associate Professor James Dahlman and collaborators developed a technique called “DNA barcoding,” which allows for the rapid, simultaneous screening of many of his custom-made delivery vehicles — what are called lipid nanoparticles, or LNPs. Scientists insert unique snippets of DNA into different LNPs, which are injected into mice. Genetic sequencing is then used to determine which barcodes have reached which cells.

Now Dahlman and Coulter BME’s Philip Santangelo are taking the screening process a step further, and they explained how in Nature Nanotechnology.

“We’re reporting an improved barcoding system that would make animal pre-clinical nanoparticle studies more predictive, speeding up the development of RNA therapies,” Dahlman said.

“Lipid nanoparticles are usually developed in mice, but when you move them into another species, like a non-human primate — because that’s the natural progression, a primate is more like a human — they frequently don’t work as well,” Santangelo said. “When they don’t, you have to go back and make adjustments.”

But what if you could streamline the process?

Using a new testing system they’re calling Species Agnostic Nanoparticle Delivery Screening, or SANDS, the

Dahlman (left) and Santangelo

Using a new testing system they’re calling Species Agnostic Nanoparticle Delivery Screening, or SANDS, the team compared nanoparticle delivery simultaneously in mouse, primate, and living human cells — all within specially engineered mice.

team compared nanoparticle delivery simultaneously in mouse, primate, and living human cells — all within specially engineered mice.

“We can actually put the same

group of nanoparticles in all three and compare delivery across species,” Dahlman said. “We found what you might expect: delivery in the primate cells predicted really well how delivery in the human cells would go, whereas the mouse cells were less predictive.”

Unlike the previous barcoding system, which worked well in mouse cells, SANDS needed a different kind of marker for screening, a molecule called reporter mRNA. Santangelo’s lab developed one, “and it basically gets around the limitations of the old system,” he said. “Now we can screen new lipid nanoparticles in mice with primate and human cells.”

Going forward, Dahlman and Santangelo believe that deeper understanding of the different mechanisms driving delivery in mouse cells and other cells will result in a more efficient selection process for LNPs, making pre-clinical nanoparticle studies more predictive and accelerating the development of RNA therapies. ‣ JERRY GRILLO

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OUR RESEARCH

This Robot’s Gentle Grip Can Harvest Berries — and May One Day Help Remove Tumors Harvesting a field full of fragile blackberries is no easy task.

Each of those juicy berries sold in the grocery store has to be collected by hand because the fruit can be easily bruised or ruined altogether. Here in the South, the harvesting window happens right in the midst of the hot summer months. Plus, all of the berries on a single bush won’t necessarily be ripe at the same time, so it may take multiple pickings to gather all the fruit.

Biomedical engineering roboticist Yue Chen is working with collaborators at Georgia Tech and the University of Arkansas on an autonomous robotic solution to this backbreaking work.

And though it’s a tool that seems far from the traditional purview of biomedical engineering, the system could lead to innovations in minimally invasive surgery one day.

“Harvesting is a very good entry point to validate this kind of soft robotics technology in real-world applications,” said Chen, assistant professor in the Coulter Department.

“I’m a medical-device person; I’m trying to develop a device that’s very dexterous, that’s very compliant, to save patients’ lives. I deal with a lot of math, engineering, and mechanics problems, and from that perspective, taking berries from a plant is quite similar to removing a

tumor from the body,” he said. “You want to identify a target, perform the path planning, reach the target, remove the target very gently, and, most importantly, avoid damaging the surrounding tissue, like a blood vessel or a nerve.”

The researchers’ first advance is a soft robotic gripper that can gently grasp and remove blackberries from the plant — damage-free. They presented the device at the 2022 IEEE International Conference on Robotics and Automation, billed as the largest robotics research gathering in the world.

The prototype gripper resembles a bulbous three-fingered hand, which is no accident. Working with experienced blackberry researcher Renee Threlfall at the University of Arkansas, the team built a sensor glove and collected data about the force required to harvest berries and pickers’ typical technique.

“First we characterized how much force the hand is generating, how many fingers we use to grasp the berries — we actually don’t use all five fingers, we use three fingers to grasp, and we characterized all of that,” Chen said.

With the force data and the threefingers insight, Chen and the team set about designing. They used the human hand for inspiration, ultimately using soft silicone and embedded force sensors for the “fingers” and a

Researchers Successfully Use mRNA to Activate Genes

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Wallace H. Coulter Department of Biomedical Engineering

This series shows a prototype soft gripping robot grasp (top) and gently pick a blackberry from its stem (bottom) during preliminary testing. (PHOTOS COURTESY: YUE CHEN)

unique tendon system for movement.

“The human hand has tendons in the fingers that help you bend and move. So, we developed tendon wires, and when we pull the tendon wire, the gripper can bend,” Chen said.

The researchers plan to explore other types of agriculture where their innovations could be useful, including a particularly famous Georgia product.

“One of the very interesting applications is harvesting peaches,” Chen said. “We’re working to optimize our system to make sure it’s more generalized.

Blackberries are challenging, because they’re very small and the surface is very fragile. But if we’re successful with blackberries, we can extend to peaches, as well.” ‣ JOSHUA STEWART

What if we could regulate the way genes are expressed? That question has long intrigued researchers, and a new study led by Emory University and Georgia Tech scientists helps narrow the knowledge gap by showing for the first time that mRNA can be used to activate genes in animals.

The investigation was led by Coulter BME Professor Philip Santangelo in collaboration with Duke University and published in ACS Nano. The work was funded by the Defense Advanced Research Projects Agency of the Department of Defense.

OUR RESEARCH

Haider Creates a Different Kind of — Literal — Window into the Brain Bilal Haider is studying how multiple areas of the brain work together for visual perception. This could help researchers understand if neural “traffic jams” underlie all kinds of visual impairments: from running a red light when visual attention is elsewhere, or problems impacting the autism-affected brain.

To do this kind of work, researchers need a reliable “map” of all the visual brain areas with specific coordinates for each unique brain. Drawing the map requires monitoring and recording data from an active, working brain, which usually means creating a window in the skull to watch blood flow activity.

Haider’s team has developed a new kind of window that’s more stable than the current standard and allows for longer-term studies. They explained how in a paper in Scientific Reports.

To get a clear image of the brain’s visual network, Haider’s lab uses an established technique called blood flow imaging, which tracks oxygen in the blood, measuring the active and inactive areas of a mouse brain while the animal views visual stimuli. To capture a strong blood flow signal, researchers typically create a cranial window by thinning the skull or removing a piece of it altogether.

These procedures can diminish stability in the awake, pulsing brain — detrimental conditions for making delicate electrophysiological measurements later on.

Santangelo and his team discovered that messenger RNA, or mRNA, could be used to control gene expression inside mice using a “dead” version of the gene-editing tool CRISPR/Cas9 while they were working on a project to develop medical countermeasures for nerve agents. The approach uses a lifeless molecule that does not create mutations in the DNA to kill the gene, but instead recruits proteins that turn on the gene.

The Duke team, led by Charles Gersbach, contributed a novel gene activator that performed better than previous designs.

“The implications of this study are significant,” Santangelo said. “This

Haider

The team’s new cranial window system allows for high-quality blood flow imaging and stable electrical recordings for weeks or months. The secret is a surgical glue called Vetbond and a tiny glass window.

work is an important stepping stone for identifying prophylactic interventions for preventing the damage wrought by multiple chemical weapons. But there is broader application potential as well.”

Using mRNA-encoded activators to regulate genes in cells inside the body offers promise of a treatment for a host of conditions: Santangelo said it could be used to treat cancer, liver disease, and infectious diseases. It could also be used to help control how the immune system responds to pathogens.

“Fundamentally, this will help us fight disease by modulating gene expression in cells. We can regulate

“Standard windows give really good pictures of the vasculature,” Haider said. “But the downside is, if you’re working with an animal learning how to perform a sophisticated task that requires weeks of training, and you want to do neural recordings from the brain later, that area has been compromised if the skull is missing or thinned out.”

The team’s new cranial window system allows for high-quality blood flow imaging and stable electrical recordings for weeks or months. The secret is a surgical glue called Vetbond — which contains cyanoacrylate, the same compound that’s in Krazy Glue — and a tiny glass window.

Basically, a thin layer of the glue is applied to the skull with a micropipette and a curved glass coverslip is placed on top of that. The cyanoacrylate creates a “transparent skull” effect. Haider’s team developed the new window system and then vetted the accuracy of the resulting visual brain maps.

“Sometimes the simplest things work.

The glue creates a barrier allowing all of the normal physiological processes underneath to carry on, but leaving the bone transparent,” Haider said. “It’s like putting a protector on your smartphone.

The protector is over the glass surface, but everything underneath stays crystal clear and functioning.” ‣ JERRY GRILLO

how cells behave and respond to harmful agents,” Santangelo said.

The research team is the first to show results on animals that have not been engineered.

“The study shows real cause and effect: when we activated erythropoietin (a hormone), we saw a boost in the proportion of red blood cells, which are the ones that carry oxygen to various parts of the body,” Santangelo said.

The next step is to test this approach in larger animals and, possibly, humans in the not-too-distant future. ‣ RAJEE SURI

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OUR RESEARCH

Seed Grant Teams Outline Progress on New Models for Health Disparities Alopecia was front and center for Valencia Watson long before Academy Award winner Will Smith and comedian Chris Rock made it topical with the smack seen round the world.

A third-year graduate student in the Coulter Department, Watson struggles with a form of the autoimmune disease, which causes hair loss and is two to six times more prevalent in Black women, like her, than in other people.

Personal experience drove Watson to study the mechanisms underlying alopecia, and she has inspired a new project and focus area in the lab of Professor Cheng Zhu. It’s one of four early-stage projects launched by the Department last year aimed at developing new tools for studying diseases that disproportionately affect people of African descent.

Ultimately, the research teams hope to develop animal models that will more closely replicate the risk factors and social determinants of health common among Black Americans.

Each received a $25,000 seed grant, “to get us started in Botchwey applying our expertise to address a very big challenge,” said Edward Botchwey, who developed the program with fellow Coulter BME faculty member Johnna Temenoff.

“Developing these systems that can model the underlying causes of health disparities will eventually allow us to bring the different aspects of biomedical engineering to bear,” Botchwey added.

ALOPECIA AREATA Alopecia is an autoimmune disorder in which T cells mistakenly attack hair follicles, and to develop a better disease model, Zhu’s team has to figure out why. Zhu credited Watson with moving the lab in this direction.

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His lab studies how immune cells sense, respond to, and adapt in a dynamic environment while being buffeted by natural mechanical forces in Cheng Zhu, principal investigator; the body.

Loren Krueger, Emory University, “We’ve used co-investigator our approach to study T cells in tumor immunology [and] infection, but not autoimmune diseases,” said Zhu, Regents Professor and J. Erskine Love Chair. “So we think it’s a good idea to include alopecia areata, because it’s one of the most prevalent autoimmune disorders in the world.”

Their work to this point has manifested in a perspective article, with Watson and fellow grad student Makala Faniel as lead authors, discussing the potential for mechanobiology and mechanoimmunology “to contribute to alopecia research by adding new methods, new approaches, and new ways of thinking,” they wrote.

BREAST CANCER When the seed grant program was announced, Haynes’ lab was already at work developing an engineered protein to activate genes that Karmella Haynes, principal are silenced investigator; Curtis Henry, Emory in triple University, co-investigator negative breast cancer cells, and she was working with Henry’s lab on developing epigenetics experiments for another type of cancer, acute lymphoblastic leukemia.

“Dr. Henry had done some exciting work showing how obese-associated

Wallace H. Coulter Department of Biomedical Engineering

serum affected epigenetics and gene expression,” said Haynes, an assistant professor. “We started thinking about how to translate this research to triple negative breast cancer, which disproportionately kills African American women.”

Their project is investigating how the biochemistry of serum in obese patients might affect epigenetic states in breast cancer, and make the disease more aggressive and deadly.

“Once we understand this, we can artificially reprogram the epigenetic state and block cancer cell replication and the formation of new tumors in other parts of the body,” Haynes said.

Led by postdoctoral fellow Cara Shields, the Haynes lab has data showing how fat cells can actually prevent cancer cell death by silencing the genes that would otherwise prevent the cancer from spreading.

Haynes and her collaborators are applying for a major external grant and plan to publish their results. First, they want to complete their investigation of gene silencing and demonstrate how epigenetic engineering can be used to activate the affected genes.

GLAUCOMA Black people are three to four times more likely to develop glaucoma than people of Asian or European descent, and it progresses faster: People C. Ross Ethier, principal of African investigator; Michael Anderson, descent are University of Iowa, and Michael six times Hauser, Duke University, are more likely collaborators to go blind.

Cydney Wong, a Ph.D. student who has taken the lead on this research in the Ethier lab, knows this all too well.

“My grandmother, who I grew up with, has glaucoma, so I have a personal interest in this disease,” Wong said. “I’ve watched as her vision

OUR RESEARCH

gradually declined. At this point she is almost completely blind.”

Her grandmother is 90 and loves hearing about Wong’s research, which is now focused on a certain genetic risk factor associated with people of African descent all over the globe.

“Our project is investigating whether a mouse expressing this genetic risk factor exhibits glaucomatous damage in its eye,” Wong said. “However, I think the more big-picture goal would be to better understand why glaucoma tends to progress so quickly in people of African descent so that we can develop treatments to prevent vision loss in these patients.”

TRAUMATIC BRAIN INJURY LaPlaca has spent the better part of her career studying traumatic brain injury (TBI). With this project, she’s attempting to probe the risk factors that can make Michelle LaPlaca, principal TBI worse — to investigator; Levi Wood, understand Georgia Tech, co-investigator why some underrepresented groups, such as African Americans, are significantly more likely to have post-TBI complications.

LaPlaca’s team is piecing together how chronic stressors and dietary factors, which have not been applied together for the study of TBI animal models before, may influence outcomes.

“I’ve been very interested in the heterogeneous factors that contribute to traumatic brain injury complications,” said LaPlaca, who was inspired by a meeting of the National Neurotrauma Society last year. “We held a session for the first time on health disparities in TBI, in which we discussed rural-urban disparities, race disparities, and social determinants. It was very timely and re-energized my interest in this area of research.” ‣ JERRY GRILLO

Oft-Ignored ‘Non-Place’ Brain Cells Play a Crucial Role in Helping Navigate to the Right Goal Visitors to Atlanta often are confounded by the various and sundry streets, roads, avenues, and drives named Peachtree (never mind the northeast, southwest, or other directional variations). Writers and late-night comedians are sure to poke fun at the region’s affinity for the name any time there’s a big event in town — and, to be sure, it can make navigating Atlanta tricky.

A new study from researchers at Georgia Tech and Emory University is shedding light on how our brains make sure we’ve reached the right road named Peachtree. And it turns out, the neurons that help us distinguish between our navigation goal and a close-but-not-quiteright goal also are impaired in models of Alzheimer’s disease.

Published in the Proceedings of the National Academy of Sciences, the paper from Annabelle Singer’s lab explains how a group of cells in the brain called non-place cells play a vital role separating the real destination, or goal, from a false one. They work in tandem with neurons in the brain’s hippocampus called place cells that help us understand where we are in space — and these non-place cells don’t look like what neuroscientists might have expected.

“Before our paper, the view is that, during navigation, there are cells that code for place, and then there are cells that do this conjunctive coding — essentially, goal plus place — but there aren’t cells dedicated purely to coding for reaching the goal,” Singer said. “And don't you think you would want that?

“These cells [we studied] are not goal cells in the way that we might have imagined them — that they fire when

you reach the goal. Rather, they fire differently between the goal and the false goal.”

The study described for the first time these non-place neurons’ unique role in separating a real goal from something that looks like the goal. Though previous studies suggested these cells played a role in spatial orientation alongside place cells, Singer’s team showed they do something additional that place cells don’t do.

“When we do the population-level decoding of neurons and these are included, we get an accurate representation of where you are in terms of discriminating between the real and the false goal, or the real goal and the rest of the track,” said Singer, McCamish Foundation Early Career Assistant Professor in the Coulter Department. “But when you exclude the non-place cells, now we can't do that decoding anymore — we can't separate the goal and the false goal.” ‣ JOSHUA STEWART

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OUR NEXT CHAPTER

A Conversation with New Chair

Alyssa Panitch

A

lyssa Panitch became the fifth permanent leader

of our unique partnership between the Georgia Institute of

Technology and Emory University in July. An experienced researcher, educator, and administrator, Panitch most recently served as executive associate dean of engineering at the University of California, Davis.

Panitch’s research focuses on inflammation as a driver of disease, and her work over the years has resulted in dozens of patents and several technologies licensed to startup companies. In this conversation, she talks about her career, her experiences, and why the Wallace H. Coulter Department of Biomedical Engineering is the perfect next step for her.

INTERVIEW by JOSHUA STEWART PHOTOGRAPH by CRAIG BROMLEY

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Wallace H. Coulter Department of Biomedical Engineering

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What makes the Coulter Department a compelling and attractive place to continue your career?

Several things. From a research perspective, Coulter BME has strength in many critical areas, and I really love the blend of basic and translational science. But the translational piece is particularly exciting. Throughout my career, it's been really important to me to work with physicians, try to understand unmet medical needs, and then focus my research on trying to solve those unmet needs and spin them out to the community.

From an infrastructure perspective, from the people who are here, and from a philosophy perspective, the Department embodies that and does that. Then, one of the other things that I have been really impressed with, even before I applied, was the attention to diversity, equity, and inclusion; it's clear from everything that comes out from the program that that's really important.

I've spent my life in public university systems because community engagement, economic improvement, and being able to bring education to first-generation students and people who are traditionally marginalized is critically important. I really feel like the Department embodies that.

endless; the challenge is focus. Where do we want to focus our energy? There are only so many resources and so much time.

The other big challenge, I think, on the education side is that demographics are changing. In Georgia, we're probably in pretty good shape, because people are going to be wanting to leave the West, where there's no water and everything's on fire. But I think we have to be mindful of the fact that demographics are changing and there won't be as many students of traditional age coming to college. How do we serve other populations to make sure that we can maintain our vibrant community?

Thinking ahead about that is going to be critical.

“I've spent my life in public university systems because community engagement, economic improvement, and being able to bring education to first-generation students and people who are traditionally marginalized is critically important. I really feel like the Department embodies that.”

One of the topics you touched on several times in the interview process was diversity, equity, inclusion, and social justice, and weaving that throughout our research and educational enterprises. What does that look and feel like? How do you bake that in even more?

We talk often about global engineering and the fact that we need low-cost diagnostics for places that don't have electricity or running water or the kinds of infrastructure that we think of in the United States. Well, we have communities in the United What are the challenges States that don't have running and opportunities facing us water and electricity. So, we in the years ahead — both need to bring that philosophy as an educational and back into the United States research organization and into some of the things Alyssa Panitch as a field more broadly? that we do and think about Biomedical engineering low-cost healthcare, low-cost has huge opportunities, as diagnostics, low-cost medical we've learned through devices and therapeutics. the pandemic. How do we make sure that we're positioned In other words, how do we serve all communities? It will be properly to go after the next big thing? Covid just showed us very important to have that discussion often. It's crucial. that we need to be prepared to rapidly understand how you We need to be teaching this to our students, graduate develop and deliver new vaccines and that we need sensitive students, postdocs and other researchers, too. I could rattle off techniques for testing to see if someone's positive with a dozen examples where we didn't have diverse engineering emerging diseases. Also, we need cures. For example, we know teams and so we have flawed devices. There are soap dispenslong Covid is a thing, but why is it a thing? And what can we ers that don't recognize dark skin. There are self-driving cars do to treat new diseases like this? We're well positioned for all that don't recognize African Americans as human. Really? of that, and there are huge opportunities there. We have this What went wrong there? We have to make sure we have tremendous partnership with Emory that’s hardwired in, but diverse perspectives and are really thinking about things; how do we build that more? I think that's a huge opportunity, otherwise, we're going to engineer flawed devices. And beyond to really further bring the two institutions together — and that, there's research going on that shows that cells from not just physicians, but blending basic science at Emory with females and cells from males don't respond the same way in other schools at Georgia Tech. The opportunities are almost culture. And most certainly, cells from people with different

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Wallace H. Coulter Department of Biomedical Engineering

genetic backgrounds don't respond the same way either.

Remembering these kinds of things as you're developing medical technologies is important, and making sure that we carry that through our classes and training activities will be important. I know that work is underway, and it must be deliberate, continuous work.

Let’s talk a bit about you. In recent years, your research has focused on inflammation as a driver of disease. Tell us about the work you’ve been doing in that area.

Sort of tongue-in-cheek, I would say that for the past 10-15 years, our research has been focused on changing the way pharma thinks about drugs. Most drugs are either small molecules that we deliver to cells to change signaling function in the cell or antibodies that we deliver to block cell receptors and change the function of the cell. The perspective of my lab is that if we change the environment in which the cell lives, then the cell will adapt to that environment and change its function. Rather than acting directly on the cell, we act on the cell environment — what we call the extracellular matrix. We design macromolecular drugs, long-chain polymers or biological polymers that we can target to disease tissue to change the cell’s environment and thereby change the way the cell is functioning to try to influence healthy tissue healing.

One example is when you have a diseased blood vessel and you need to put in a stent. The physician goes in with a balloon catheter, they inflate the balloon to push open the blood vessel, and then they place a stent. When they push really hard on the inside of the blood vessel to open it up, they damage the inside of the blood vessel. And when that happens, the body sees damaged tissue and tries to repair it. It's going to cause an inflammatory response, because we need some sort of inflammatory response for repair. But that isn't normal inside a blood vessel. Instead, what if we deliver a biological polymer that binds right to where that damage is and looks like the native inside of the blood vessel — will that then make the cells respond like it's healthy and facilitate healing of the blood vessel?

We've done some clinical trials in Australia and New Zealand on that, and it looks really good. There's a company pushing that forward to see if we can bring it into use.

We've also worked a lot in the cartilage and osteoarthritis space as well as wound healing for burns and diabetes.

You’ve been involved in several startups and have something like 30 patents in the U.S. Why is that kind of innovation and startup activity crucial to what we do?

As biomedical engineers, we’re trying to improve human health. I learned from my postdoc advisor that if you really want to improve human health, you have to patent new ideas, because companies won't develop something if they don't think they can make a profit. There are very few exceptions to that. So, if you really do want to improve human health from a therapeutic perspective, patenting is a critically important piece of what we do. And I learned very early on that if you are careful about it, you can patent and publish

essentially at the same time, and we can fulfill our academic mission of furthering knowledge and sharing knowledge while also patenting.

Aside from your professional life, what should we know about you? What do you like to do when you’re not in the lab or teaching or running a department?

I do have a little bit of a work-life balance! That is really, really, really important. I do blend things in. I have sat on the side of soccer fields and put together entire tracks for conferences. I'm sort of a health nut. I like to cycle and run and do yoga. I enjoy really good food, and I love to cook. And family and friends are important to me.

I'm really excited to be in Atlanta. I’ll be able to walk to Georgia Tech, and I can get to Piedmont Park pretty quickly to go running. And the Appalachian Trail is not so far away.

I grew up on the other end of the Appalachian Trail, so I'm excited about that and to be able to get up into the mountains and hike. I've heard that Atlanta is really becoming a foodie place, and I have already experienced some great restaurants. And I’m excited just to be in a different culture. •

FOR THE LAST YEAR, the Coulter Department has continued to advance our mission under the leadership of Machelle Pardue, who served as interim Wallace H. Coulter Department Chair. Pardue remains part of the Department’s leadership team as associate chair for faculty development.

“Machelle has my deep admiration and heartfelt thanks for her talented, steady leadership over the last year,” Panitch said. “She has been a tremendous partner over the last few months, helping bring me up to speed and answering my many questions. I am grateful for all she continues to do for me and for our community.”

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CREATIVITY'S

SPARK From Surgical Tools to Virtual Medicine, Student Innovators are Leading the Way on Improving Lives

by JOSHUA STEWART, JERRY GRILLO, & JANAT BATRA

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Wallace H. Coulter Department of Biomedical Engineering

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J Below from left: Tony Wineman, Cassandra McIltrot, Marzeah Khorramabadi, and Neel Narvekar display the StrideLink device and components.

(PHOTO COURTESY: TEAM STRIDELINK)

ared Meyers was on a plane back to Atlanta when he struck up a conversation with the couple sitting next to him. One of them was a retired urologist, and after their talk, Meyers was inspired.

Before long, he had assembled a group of entrepreneurially minded friends and started talking to other urologists. They learned about catheter-associated urinary tract infections, a common problem for patients with long-term catheters, and set out to help.

They created a noninvasive, app-connected bladder sensor that alerts patients when they need to empty their bladders. Then they formed a startup company to develop the device.

Already, they’re attracting national accolades and participating in accelerator programs, and they’re just one of several student groups who are making waves with innovative ideas.

Sometimes the ideas come from unexpected conversations — Cassandra McIltrot and Marzeah

Khorramabadi have turned an afternoon chat on the porch into a new way to help physical therapists analyze gait and help patients at risk for falls.

Other times, the ideas come from senior design projects where clinicians offer a problem and the students create compelling solutions — like a stethoscope designed for telemedicine, a fetal heart monitor for low-resource countries, and a surgical tool that could help doctors more quickly access and remove a brain-killing blood clot.

What they all have in common, though, is the students’ drive to make lives better, whether in their neighborhood or halfway ‘round the world.

No-Guesswork Gait Analysis StrideLink is a shoelace-worn device created by McIltrot, who finished her biomedical engineering degree in the spring, and Khorramabadi, a now-graduated computer science student.

With a unique step recognition algorithm, the device can collect concrete data about

an individual’s walking patterns. This can help physical therapists with gait analysis, the measurement of the body’s movements, mechanics, and muscle activity.

Gait analysis is important for stroke and cerebral palsy patients, in chiropractic practices, and for other conditions. Currently, gait is measured by the naked eye as physical therapists watch their patients walk and note any patterns or errors. That can make the process highly subjective and prone to error. StrideLink replaces that subjectivity with hard data.

The device started with the nugget of an idea in the summer of 2020. McIltrot and Khorramabadi were sitting on the porch discussing McIltrot’s research related to fall risks for older adults.

“We thought to ourselves, why don't we do something about this?” McIltrot said. “We started with that small seed — why do elderly people fall all the time?

— and we now have a real product to fix that technology gap.”

Before even attempting to design a solution, the friends spent six months researching and interviewing physical therapists. They wanted to understand how they conducted gait analysis without any aiding technology and what their needs were. As the duo began to formulate a design, they recruited team members Neel Narvekar, CmpE 2021, and Tony Wineman, EE 2021, who helped them develop a prototype and a custom step-analysis algorithm.

Then they set out to test their approach, recording gait cycle time and time spent in different phases of walking. The only device they could find as a benchmark was a $40,000 gait system in a lab. When the team tested

StrideLink against that system, the margin of error was much lower than expected.

“We built this device for less than $100 in four months with a team of undergrads, and we were getting comparable results to a $40,000 system that's been the gold standard for over 20 years,” Khorramabadi said. “That’s something that you don't really expect when you're designing a device that early on.”

The team is refining their device and working with physical therapists to pilot it in real-world settings.

Above: The StrideLink device is worn on the shoelaces for gait analysis. Below: The device's custom hardware.

(PHOTOS COURTESY: TEAM STRIDELINK)

“We built this device for less than $100 in four months with a team of undergrads, and we were getting comparable results to a $40,000 system that's been the gold standard for over 20 years.”

Marzeah Khorramabadi

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Clot-Busting Via the Carotid

Top: Members of Team carSEAL hold scaled-up versions of their device at the Fall 2021 Capstone Design Expo. The device is designed to close the carotid artery after a clot-removing catheterization for stroke patients.

(PHOTO: JOSHUA STEWART)

Inset: Team carSEAL outside the Mayo Clinic in Jacksonville. The team includes, from left, Joshua Cruz, Nicholas Lima, Derek Prusener, Shovan Bhatia, and Giancarlo Riccobono.

(PHOTO COURTESY: TEAM CARSEAL)

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The carSEAL device is designed to help significantly reduce the time it takes to perform a lifesaving thrombectomy after a stroke — a procedure where a catheter is inserted through the femoral artery in the leg and snakes its way through blood vessels to remove a clot, usually in the cerebral arteries.

“It’s generally a successful procedure, but it can take about an hour to go from your leg up to your brain,” team member Joshua Cruz said. “When you’ve had a stroke, time is everything; you can lose hundreds of millions of neurons in an hour.”

Surgeons have demonstrated that inserting a catheter through the carotid artery can cut the procedure time in half, but there aren’t any approved devices to seal the critical artery afterward.

“The great thing about this device is, it not only closes the carotid artery — one of the most difficult blood vessels to close — but it’ll close any other blood vessel, which makes it

Wallace H. Coulter Department of Biomedical Engineering

an extremely competitive product,” Cruz said.

“We designed it for neurosurgeons, but we think it’ll have applications for interventional cardiologists, radiologists, and others.”

The team — Cruz, Shovan Bhatia, Nicholas Lima, Derek Prusener, and Giancarlo Riccobono — tackled the problem at the request of Mayo Clinic neurosurgeons as part of the BME Capstone Design course. Their proof of concept has been so promising, and their Mayo Clinic sponsors so enthusiastic, that the group has continued to refine the device even as the

members finished their degrees and moved on to medical school and jobs. They’re focused on moving toward the pre-clinical studies necessary for U.S. Food and Drug Administration evaluation.

Along the way, they have worked with students in Coulter BME’s Cardiovascular Fluid Mechanics Lab to test carSEAL’s effectiveness and scale down their proof-ofconcept model to the actual size for arteries.

“I am extremely proud of our team’s achievements in the short time we have worked together,” Bhatia said. “CarSEAL has gained a lot of traction already, and we are excited to see how far we can take this — hopefully bringing carSEAL to clinical practice within a few years.”

A Long-Distance Ear The creators of the AusculBand are focused on a more basic kind of problem for doctors in this new age of virtual office visits.

The five recent biomedical engineering graduates developed a long-distance stethoscope that provides real-time and pre-recorded data to physicians. The device greatly expands virtual exam capabilities, allowing a physician to listen to a patient’s heart, lungs, and abdominal sounds and provide a more comprehensive assessment during a virtual visit.

“Access to healthcare is one of the biggest problems in the field,” said co-inventor Keval Bollovaram, noting that almost 50 million Americans live more than an hour’s drive away from the nearest hospital, but 96% of those people have access to a mobile device. “We believe telemedicine is the solution to getting these people the healthcare they deserve.”

Even among people who live close to healthcare centers, telemedicine is booming, expanding the need for technology to improve the quality of virtual visits. The group’s AusculBand digital stethoscope is easy for patients to use at home, where they can record cardiac and pulmonary sounds or let the doctor listen live during a telehealth visit.

“The use of telemedicine has been catalyzed by the Covid-19 pandemic,” Bollovaram said. “While the world has suffered from the pandemic, we think that now is the perfect time to develop new solutions to address the evolving healthcare environment.”

Co-creator Sil Savla said the team tested frequency response of the device’s internal circuitry and a did a noise comparison test against devices already available. They

found the AusculBand was more than 50% clearer than the leading digital stethoscope.

The group — which also includes Ram Akella, Ahdil Gil, and Atharv Marathe — has applied for a patent, and the members already have won support for their device from the National Institutes of Health DEBUT Challenge. They’ve formed a company and are pursuing other funding through Emory startup programs and elsewhere.

The AusculBand is a long-distance stethoscope that patients can use at home to expand virtual exam capabilities. (PHOTO COURTESY: AUSCULBAND)

Almost 50 million Americans live more than an hour’s drive away from the nearest hospital, but 96% of those people have access to a mobile device.

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Frugal Fetal Monitoring A low-cost fetal heart monitor designed by biomedical engineering students for communities in Ethiopia also started as a senior project and has since won national design competitions for global health solutions.

The Heartone device aims to help doctors and midwives in Ethiopia monitor babies in the womb for potential complications during birth. Problems occur in a quarter of all births

Top: Kadidia Haidara (left) and Carina D’Angelo (right) demonstrate their device at the Capstone Design Expo.

(PHOTO: JOSHUA STEWART)

Right: A laptop displays sample fetal heart rate data alongside the prototype Heartone device at right atop a simulated womb.

(PHOTO: JOSHUA STEWART)

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Wallace H. Coulter Department of Biomedical Engineering

in Ethiopia — and low- and middle-income countries overall see 2.5 million stillbirths each year. Fetal heart monitoring is a critical tool for identifying when a baby is in distress and intervening early, but the gold-standard devices cost hundreds of dollars and are difficult to deploy in countries with limited resources.

Heartone adapts the current standard of practice in Ethiopia, which involves using a simple amplification device called a pinard horn to listen to fetal heart rates. The team — Carina D’Angelo, Lydia El-Sayegh, Kadidia Haidara, Deborah Lobaccaro, and Madeleine Tincher — combined a horn-shaped device with a microphone and built an algorithm to filter out noise and track heart rate over time.

Their initial testing found it was more than 95% accurate in calculating fetal heart rates.

“One of the essential aspects we’ve focused on has been designing our device to be as effective as possible while still being inexpensive and easily repairable in low-resource settings,” El-Sayegh said. “We’ve dedicated a lot of time working on getting the clearest signal possible into our algorithm by soundproofing, sealing, and making other modifications to the hardware.”

Along the way, they’ve also enlisted graduate students and experts in signal processing to refine their algorithm. The idea is to provide a fully functional app with the Heartone device that does all the processing and tracking of fetal heart rate

“We founded Augment Health, Inc. to commercialize this invention so we can get it into people’s hands and help them to achieve improved peace of mind and quality of life.”

Jared Meyers

trends to help users monitor the baby’s health.

The team developed their device as part of the Coulter Department’s Global Health Capstone program founded by Professor of the Practice James Stubbs. They’ve also been advised by Research Scientist Kelsey Kubelick. In the spring, they won the 2022 Rice360 Global Technologies Design Competition, earning funds and making connections with physicians and engineers around the world to help them refine their device.

Smart Sensors for Indwelling Catheters From that happenstance airplane conversation, Jared Meyers and his partner Stephen Kalinsky have become convinced they have a chance to change lives. They’ve formed a startup called Augment Health to help patients with indwelling catheters regain independence.

As they learned about catheter-associated urinary tract infections, they thought catheter valves seemed like a great option for patients with spinal cord injuries or other neurological conditions that force them to rely on long-term catheters.

But: “We realized that surprisingly few people actually use [catheter valves],” said Meyers, who finished his degree in May. “We asked ourselves, ‘Why not?’ and then we realized — because many people can’t tell when to empty their bladder.”

With Camille Díaz, who has since left the project to focus on pre-med coursework and then

medical school, Meyers and Kalinsky designed a noninvasive sensor that sits between the catheter and the catheter valve. It sends notifications to a smartphone or wearable device, like a smart watch, when the user’s bladder is full.

“We realized the magnitude of the problem when we started talking to people who live with indwelling catheters,” Meyers said. “In these conversations, we learned that urine collection bags could make people too embarrassed to go outside, unable to go in the pool, and risk accidents and leakage during physical activity.

Some wheelchair users even told us the ability to use the bathroom more normally would be a higher priority than being able to walk again.”

Established innovators believe in the pair’s idea: Augment Health won cash, mentoring, and an accelerated patent filing from the National Inventors Hall of Fame. The company also participated in a Memphis-based medical device accelerator to help them get their product through regulatory review.

“We founded Augment Health, Inc. to commercialize this invention so we can get it into people’s hands and help them to achieve improved peace of mind and quality of life,” Meyers said. •

Top: Augment Health founders Jared Meyers, left, and Stephen Kalinsky.

Bottom: The Augment Health Bladder Management Device is a sensor that fits between a catheter and catheter valve and sends notifications to a smartphone or other device when the user's bladder is full. (PHOTOS COURTESY: AUGMENT HEALTH)

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A BREATH OF

HOPE CUSTOM 3D-PRINTED AIRWAY SPLINT IS GIVING ONE LITTLE GIRL A CHANCE AT LIFE

Ramiah Martin isn’t like other little girls, and that’s perfectly fine with her mother.

“She is nothing short of a miracle,” Leanne Martin said of her daughter, who was facing long odds before her birth in December 2017.

Initially, she was diagnosed with heart problems during a prenatal ultrasound. The odds only got worse when Ramiah was born with an extremely rare developmental abnormality called tracheal agenesis — she didn’t have a trachea, or windpipe.

About one in 50,000 babies worldwide are born with the condition, which is almost always fatal.

But in December 2021, Ramiah and her family celebrated her fourth birthday thanks to the work of physicians at Penn State Health Children’s Hospital and a 3D-printed tracheal replacement splint developed by researchers in the lab of Scott Hollister in the Coulter Department.

“We know that children with this condition have not survived past the age of eight or 10,” said Hollister, professor and the Patsy and Alan Dorris Chair in Pediatric Technology. “Our fingers

are crossed that this case will be different.”

This case is indeed different. It is the first time such a device has been used to treat tracheal agenesis, and Hollister is part of the team of researchers who authored a clinical case study published in the journal JTCVS Techniques.

The splint — known as the Airway Support Device — already had a strong track record, having been used in the successful treatment of other pediatric patients.

In those cases, the split treated tracheabronchomalacia, a collapse of the windpipe, which causes severe, life-threatening airway obstruction.

While a professor at the University of Michigan, Hollister collaborated with colleague Glenn Green to develop the first version of a 3D-printed, patientspecific airway splint that is bioresorbable — it can be naturally and safely absorbed by the body. The small device is a lifesaving scaffold that opens a child’s windpipe, allowing them to breathe.

But Ramiah’s case presented a new, daunting challenge. She didn’t really have a windpipe to work with. Her esophagus was her windpipe.

by JERRY GRILLO

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Because of its previous success, and because there were no other options, doctors got permission to use the 3D-printed splint under the “expanded access” rule — sometimes called “compassionate use” — which allows fast access to medical devices for life-threatening cases like Ramiah’s.

“Tracheal agenesis is a very unusual clinical case with few positive solutions,” said the study’s lead author, Dr. Anthony Tsai, Ramiah’s surgeon and co-director of the Surgical Innovation Group at Penn State Health Milton S. Hershey Medical Center. “I knew about the work Scott and Glenn had been doing, and I’d seen their success in using the device for airway issues that are not as dire. But similar principles are in play, and that’s what we needed.”

They needed the support of a splint to keep her airway open, but this time with an added wrinkle: Ramiah’s surgical team needed a splint that would help her esophagus do the work of an airway.

A Lifesaving Procedure Ramiah needed surgery almost immediately after being born. Essentially, the surgical team disconnected her lower esophagus, which feeds the stomach, from her upper esophageal airway — she could take nutrition directly into her stomach through a G-tube. And then they had to turn the upper portion of her esophagus into a trachea, creating a pseudo-tracheostomy, a surgical opening in the neck to provide a direct route for air to reach the lungs.

“That isn’t a long-term solution,” Tsai said. “We prevented air from getting into the stomach and created a pathway to push it into the lungs, but it isn’t sustainable.

When you take a deep breath, the esophagus collapses, so then you can’t get enough air into the lungs.”

With Ramiah sedated, ventilated, momentarily stabilized, and just a few days old, Tsai and his colleagues discussed more permanent options for her airway reconstruction.

That led them to Hollister and his 3D-printed splint composed of polycaprolactone, a biodegradable polyester.

Because of its previous success, and because there were no other options, Tsai and his team got permission to use the device from the U.S. Food and Drug Administration under the “expanded access” rule — sometimes called “compassionate use” — which allows fast access to medical devices for life-threatening cases like Ramiah’s.

Hollister’s team re-engineered the Airway Support Device, adding some curvature to accommodate the stoma in Ramiah’s neck. The device was ready and installed during airway reconstruction surgery when Ramiah was just 20 weeks old.

She gradually progressed and went home when she was a year old, still needing mechanical ventilation. Further tests and imaging showed that her airway was improving, and when Ramiah was two years old, she started breathing on her own in the daytime, resting easily at night on a ventilator for safety.

Later, doctors used tissue from her colon to rebuild Ramiah’s lower esophagus, which should eventually allow her to take in food through her mouth. Though she is developmentally delayed, Ramiah is crawling and pushing a walker around, learning to communicate through sign language, going to preschool, and playing with her sisters.

“We’re very low key about celebrating holidays,” Leanne Martin said. “But we recognize the gift of each

Preschool is a typical part of Ramiah Martin's busy day. (PHOTO COURTESY: LEANNE MARTIN)

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Wallace H. Coulter Department of Biomedical Engineering

Scott Hollister (above) and his colleagues have designed a lifesaving 3D-printed airway splint that has been used to successfully treat a previously untreatable condition in newborns. The Airway Support Device (inset) is made of biodegradable material that is naturally and safely absorbed in the body. (PHOTOS: ALLISON CARTER)

year, and we always thank God for that. We knew that Ramiah was leading us into uncharted territory.”

Ramiah may need another 3D device as she gets older to stabilize her reconstructed airway, Martin said.

But right now, she is thrilled that Ramiah has started taking steps on her own — no walker required.

“That is the kind of outcome we all hope for,” said Hollister, whose Coulter BME collaborators Sarah Jo Crotts and Harsha Ramaraju were major contributors to the work.

“We’re excited, because we think this is the beginning of a new paradigm for children with this rare condition.” •

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Wallace H. Coulter Department of Biomedical Engineering

What’s next for the research team credited with the wide availability of at-home Covid tests

by JERRY GRILLO

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T

oday, at-home diagnostic tests for Covid-19 are available in every drugstore. But two years ago, in the early stages of the pandemic, it was a much different story.

We can all thank a group of researchers at Georgia Tech, the Emory School of Medicine, and Children’s Healthcare of Atlanta for the now-routine access to these tests. They answered a call from the National Institutes of Health Rapid Acceleration of Diagnostics program (RADx) and led a national effort to validate these point-of-care tests for the deadly virus.

With more than $60 million, the consortium was charged with selecting and testing the most promising Covid diagnostic tools and guiding them quickly through the development and commercialization pipeline. Along the way, that initial mission expanded, including testing diagnostics for the different Covid variants that have emerged.

“It’s almost like that movie Groundhog Day — every time a new variant pops up, we validate every test again to make sure they work against the variant,” said Wilbur Lam, professor in the Coulter Department of Biomedical Engineering and one of the project leaders. “We report our data straight to the FDA and they act on that. Our center

here in Atlanta is directly affecting national health policy, which makes this an exciting place to be.”

And there’s plenty more going on and coming up for the Atlanta RADx team.

In the fall, Lam and his colleagues published a study in the Journal of the American Medical Association showing that school-aged children can successfully use a nasal swab on themselves for Covid testing. The research should have immediate implications, as it provides data supporting recommendations for schools and other settings where children regularly undergo Covid-19 testing.

“Kids as young as four years old can swab them selves adequately,” said Lam, who is a pediatric hematologist and oncologist at the Aflac Cancer and Blood Disorders Center of Children’s and professor in Emory’s School of Medicine.

Typically, a health care worker collects samples for children’s respiratory tract issues, a challenging scenario when repeat testing is required in school and group settings because there simply aren’t enough clinically trained staff to do the job. Student self-swabbing can safely reduce the staff workload. The idea for the study grew out of discussions between RADx and U.S. Food and Drug Administration researchers, according to Lam. “The FDA is now actually changing its policies so that any technology and diagnostic company that has an authorized Covid-19 test out there can basically just say, ‘Because of the Atlanta group’s research, we now will change our indications to include kids,’” Lam said. “This has huge implications for all of us who have children.”

Left: An elementary school child swabs his own nose for a Covid-19 test. The RADx team has published findings in the Journal of the American Medical Association that school-age children can effectively use a nasal swab on themselves for testing. (PHOTO: ISTOCK) Opposite: A drive-through testing site in Brookhaven, Georgia, (bottom) is an independent testing site for the RADx program where participants are helping assess new rapid Covid tests. Inside (top left), Lauren Finley and Delatria Palacios record testing data. Scientists Leda Bassit and Nils Schoof (top right) work in the Biosafety Level 3 laboratory at Emory, where they can use live SARS-CoV-2 samples to test the effectiveness of Covid-19 tests.

(PHOTOS COURTESY: ACME POCT & RADX ATLANTA TEAM)

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Wallace H. Coulter Department of Biomedical Engineering

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“We will be forming a new diagnostic center to accelerate the invention, development, and translation of point-of-care diagnostic tests of all types.

We’ll take the best of everything we’ve been doing with RADx and apply it to new technologies.”

Wilbur Lam

New App for the Old Model There wouldn’t be an Atlanta RADx team without ACME POCT, the Atlanta Center for Microsystems Engineered Point-of-Care Technologies. Funded by the NIH and established in 2018, ACME POCT is one of four centers in the country focused on advancing point-of-care technologies — that is, diagnostic testing that is done conveniently at home or at the bedside rather than in lab.

“When we pivoted for RADx during the Covid pandemic, we already were doing device evaluation and working with inventors, investigators, and small companies who were developing new diagnostics.

We would provide funds and income support and the resources to help them,” said Greg Martin, a

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Wallace H. Coulter Department of Biomedical Engineering

RADx project leader and one of the principal investigators of ACME POCT along with Lam and Georgia Tech microsystems engineer Oliver Brand.

“We’ve expanded our capabilities quite a bit through RADx. We expanded our abilities around regulatory strategies and pathways to help companies move their technologies through the process and to reach the public,” added Martin, professor in Emory’s Department of Medicine.

“Also, we’ve focused more on usability, particularly for consumers using over-the-counter tests,” Martin said. “Not everyone has the same visual acuity. Not everyone has the same physical or manual dexterity. There are a lot of important issues related to usability and accessibility.”

Among them: user bias. With the FDA’s support, the RADx team is looking deeper into how users are reading their test results — for example, how does a mildly positive test result affect a person’s decision to go on vacation or go to work?

These studies bring the diagnostics scientists and engineers together with researchers at Georgia Tech’s HomeLab in the Ivan Allen College of Liberal Arts.

HomeLab’s multidisciplinary team of researchers generally focus their work on older adults living at home. But their work in evaluating the safety, efficacy, usability, and accessibility of products translates well to the RADx and ACME POCT mission.

Expanding the Mission ACME POCT, with or without the RADx designation going forward, enters a post-pandemic era equipped for an expanded mission, according to Lam and Martin: “The NIH is asking us to submit a bid to be the test verification center for new diagnostics beyond Covid-19,” Lam said.

Even if that isn’t in the cards, he added, “the leadership at Emory and Georgia Tech are asking what’s next. So, we will be forming a new diagnostic center to accelerate the invention, development, and translation of point-of-care diagnostic tests of all types. We’ll take the best of everything we’ve been doing with RADx and apply it to new technologies.”

The idea is to focus on patients and end users as well as local and regional inventors developing the technologies, including faculty and student researchers at Emory and Georgia Tech.

“We can serve as an independent assessor for diagnostics in other areas of need in our community, our world,” Martin said.

He identified one area particularly relevant in Georgia and the South: “The NIH has identified maternal health as a key area of need, because we in the U.S. simply don’t perform as well in maternal

health as other developed countries. This is a huge opportunity for making improvements.”

For example, there are opportunities to vastly improve infection surveillance and screening in a timely and safe way for the mother and the unborn child and to screen for other potential problems, such as postpartum hemorrhage — is the mother at clinical risk for excessive bleeding during delivery?

“We can build better point-of-care diagnostic tools for doing these assessments in the home or the clinic,” Martin said.

ACME POCT’s mission always has been a bit more wide-angled, he said. Covid-19 added a tightened focus in a global emergency.

“We do things around cardiovascular diseases, cancer, lung diseases, and infectious diseases,” Martin said. “But the NIH has identified other areas of significant need, and we can now apply the expertise we developed in RADx and bring that into ACME POCT ecosystem.”

As they develop an expanded diagnostics research center, Lam said health equity has been a significant part of the discussion — another lesson learned from the Covid experience.

“These tests that we’ve evaluated, unfortunately, always help people with access and resources first.

Ironically, the people that need them most often can’t afford them or don’t have access,” Lam said. “How do we move forward and develop new technologies but at the same time ensure equity? As these diagnostics become more decentralized, what does that mean for us as a society? How do we set policy, and who owns this data from these tests we’re using in the home?

“There are a lot of interesting questions and implications, and we intend to study all of that.” •

Top: One of the first devices the Atlanta RADx team evaluated was the Accula, a 30-minute point of care test developed by MesaBiotech, now Thermo Fisher Scientific.

Bottom: A collection of SARS-CoV-2 variant samples prepared by the team for evaluating rapid Covid-19 tests. The work became a bit like the movie Groundhog Day as the team reevaluated tests when new variants of the coronavirus emerged. (PHOTOS COURTESY: ACME POCT & RADX ATLANTA TEAM)

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OUR COMMUNITY

Our Community Cassie Mitchell Wins Silver in Tokyo Paralympics with Record Club Throw

(PHOTO: MARK REIS/U.S. PARALYMPICS TRACK & FIELD)

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Cassie Mitchell overcame a cancer diagnosis and a yearlong pandemic delay to reach the Paralympic Games podium again.

The biomedical engineering assistant professor has added another silver to her collection of Paralympic medals, placing second in the F51 club throw in Tokyo at the 2021 Games.

In fact, it took a Paralympic record to beat Mitchell, who herself threw a Paralympic-record 24.18 meters before world-record holder Zoia Ovsii from Ukraine topped her. Still, Mitchell’s throw was a personal best and will go in the history books as an American record for F51 throwers.

As a result, Mitchell got a portion of what she went to Tokyo to achieve: “I want to see the American flag raised; I want to hear our national anthem. It's the process and what it means to ‘never, never, never give up’ to reach the top, and to compete with honor for the USA,” Mitchell said before the Games. “I'm sentimental and very patriotic when it comes to competing for Team USA.” The Tokyo Games were the third consecutive Paralympics for Mitchell.

Before leaving for Japan, Mitchell said

Wallace H. Coulter Department of Biomedical Engineering

she felt an exceptional competitive fire this year. It paid off with world No. 1 rankings in both discus and club throw in the F51 classification. She finished fourth in discus, where she faced athletes with greater function in their limbs.

Paralympians are grouped into classifications according to their disability. Mitchell is classified as a 51 athlete; they are the most severely disabled athletes who have impairments in all four limbs (the "F" refers to field athletes). Several classifications were combined for her discus event.

That was just the latest shift in Mitchell’s long athletic career. She has shifted sports over the years as the landscape of Paralympic sports changed for quadriplegic athletes with Mitchell’s level of disability. Her events have also changed because of a medical condition: Before the Rio Games in 2016, she was diagnosed with leukemia, a condition for which she is still being treated.

No matter. Before boarding a plane for Tokyo, Mitchell said she had a feeling she’d be strong in club throw.

Turns out, she was right.

‣ JOSHUA STEWART

OUR COMMUNITY DAVID BAT, BME 2021 One thing I have learned through BME at Georgia Tech is how to work collaboratively with others. With so many courses that implement problem-based learning and group work, I have learned to work in groups of all sizes — with both friends and strangers (who later become friends) and who all have different skills and backgrounds.

It has definitely prepared me to enter the medical device industry following graduation.

Ellerbe Wins PeproTech’s Inaugural Diversity Scholarship Lela Ellerbe says she knew from a very young age that she wanted to change the world.

Now the company PeproTech is joining her in that journey, selecting the third-year biomedical engineering student for its first Diversity Scholarship. The award includes mentoring and professional development opportunities in addition to covering Ellerbe’s tuition and room and board. And she said it has freed her to focus on achieving her dreams.

“College is very expensive, especially as an out-of-state student, and finding a way to pay for it is not something you can push to the bottom of your to-do list,” Ellerbe said. “Winning this schol-

arship alleviated some of that worry. I am now able to focus on getting good grades, volunteering more, and being more mindful of my college experiences.”

In practical terms, that has meant devoting time to seminars, conferences, and other networking and development opportunities, Ellerbe said, including some that have come with PeproTech’s own professionals.

Ellerbe has participated in virtual lunches with company managers and learned about the cytokine products PeproTech produces for research labs.

She also traveled to the company’s New Jersey headquarters for a tour and meeting with their president.

‣ JOSHUA STEWART

Song Honored as One of Georgia Tech’s Faces of Inclusive Excellence Biomedical engineering Research Scientist Hannah Song was selected as one of Georgia Tech’s Faces of Inclusive Excellence for 2021.

Song was cited for her leadership and work mentoring a diverse team of undergraduate researchers focused on sickle cell disease in Manu Platt’s Lab. “I have worked with students from so many backgrounds and countries. All of them bring different perspectives on science and engineering,” Song said. “Their background might be different, what’s driving them might

be different, but we all bring different flavors to the same goal. And I always tell them, ‘I will teach you as much as you would like to learn, no matter where you are from. And in the end, you will teach me something new as well.’”

Each year, Georgia Tech honors students, researchers, faculty, and staff across campus who embody the Institute’s work to expand access and lead by example in building a more inclusive community. Song was one of 64 people recognized for 2021. ‣ JOSHUA STEWART

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OUR COMMUNITY

Using Advanced 3D Printing, Undergrads Design Adjustable Golf Putter Above: From left, Georgia Tech alumnus Reagan Cink, undergraduate researchers Caroline Means and Brittan Pero, and pro golfer and Tech alumnus Stewart Cink at Bobby Jones Golf Course in Atlanta. The elder Cink helped consult on the putter design by Means and Pero, along with the pros at Bobby Jones Golf Course.

(PHOTO: CANDLER HOBBS)

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A Coulter BME undergraduate spent the first year or so of the pandemic working on a project that could make it easier for golfers and equipment makers to experiment with putter characteristics.

The project’s goal is to allow golfers to adjust parts of their club to find a better stroke, rather than having to buy a new club. It also could help equipment manufacturers reimagine their prototyping and design process.

Caroline Means designed a unique putter using an advanced metal-depositing 3D printer that is typically used to make aircraft parts. Working with Jud Ready, principal research engineer at the Georgia Tech Research Institute, the idea was to be able to adjust the putter’s key characteristics, toe hang and loft, and explore new kinds of face materials.

“We wanted to design a club that was able to be customized to a golfer in those three areas without having to get a new

Wallace H. Coulter Department of Biomedical Engineering

club or go to a professional and have them bend your club, and without significantly and permanently altering the structure or composition of the club,” said Means, who pursued the idea as part of a President’s Undergraduate Research Award at Tech. “There hasn't been as much innovation in the area of putter heads, so we decided to take on that challenge.”

The team’s prototype putter is made from stainless steel (eventually they’ll explore a multi-material composition), with an innovative shaft attachment method that allows for continuous adjustment of the toe hang. Its face inserts are made of either metal or a polymer created by Carbon, a California-based 3D-printing company. The inserts come in a variety of angles to adjust the club’s loft. They can be combined or stacked and easily removed via a unique attachment system Means and Ready created.

“The 3D printing gives us an advantage

OUR COMMUNITY to create structures that could not be machined through traditional methods,” Means said. “That means that after it's been manufactured, a golfer can pick what face surface material they want for the putter. They can decide how many degrees of loft is best for the green conditions that day. As their swing

the face during their swing. Changing the toe hang can help the putter and the golfer’s swing work together for improved directional control of the ball.

Loft is the angle of the putter face when it rests on the green — usually just a degree or two. Too little loft, and the ball is pushed into

The project’s goal is to allow golfers to adjust parts of their club to find a better stroke, rather than having to buy a new club. It also could help equipment manufacturers reimagine their prototyping and design process.

changes and improves, they are able to adjust the toe hang of the golf club.”

Perhaps it’s worth pausing for a quick putter primer: Toe hang is a measure of the center of gravity of the putter, which affects how the clubhead moves during a stroke. The idea is to hit the ball with the putter’s face squared up, but every golfer’s stroke is different, and most rotate

the green when the putter hits it, slowing it down; too much, and the ball may hop at contact instead of rolling.

All of that affects whether the ball reaches its intended target: the bottom of the cup.

To create their patent-pending design, Means and Ready contacted the golf pros at Atlanta’s historic Bobby Jones Golf Course. They also enlisted a pretty famous Georgia Tech alumnus who knows a thing or two about golf clubs.

“I come from a unique perspective on things like product development and innovation,” said Stewart Cink, a former Tech golfer and eight-time winner on the PGA Tour. “I've got the on-course experience and knowledge, and I've been through a lot of product innovation with companies that I've worked with in the past. Jud had no way of knowing that it would be something that I would like really like, but this is part of my job that I really enjoy doing.”

So how does a biomedical engineering student end up elbowsdeep in golf putter design?

Means met Ready when she took two of his courses, including Materials Science and Engineering of Sports. In

SEE THE PUTTER DESIGN IN ACTION https://bit.ly/3D-putter

Above: The adjustable golf putter created using an advanced metal-depositing 3D printer. (PHOTO: CANDLER HOBBS) Below left: Reagan Cink takes a few test putts at the Bobby Jones Golf Course Bandy Instructional Center. (PHOTO: JOSHUA STEWART)

the class, they visited Georgia Tech’s Advanced Manufacturing Pilot Facility, where they learned about a specialized 3D printer that uses metal powder and lasers to build metal objects. Before long, Ready and Means were thinking about golf clubs and how they might be able to innovate while exploring the potential of the machine.

“My background in biomedical engineering really came in strong. We spend a lot a lot of time focused on learning how to put users at the center of the design process,” Means said. “I talked to professionals at Bobby Jones Golf Course to learn what makes a person come back to a putter. Our team wanted to know what kind of things they have to account for when they're fitting a club to someone, and how we can make this something that is unique and that people will want to use.” ‣ JOSHUA STEWART

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Former PhD Student Douglas-Green Returns to Coulter BME as a Faculty Member A year into her postdoctoral work, Simone Douglas-Green has accepted an offer to join the Coulter BME faculty starting in early 2024 — a long lead, but a reflection of her talent and part of an effort by the Department to welcome back promising young scholars who earned a doctorate in the joint Emory University-Georgia Tech program.

“I want to solve complex problems, and the BME program at Georgia Tech and Emory is the supportive environment where I can pursue my research vision and take risks,” said Douglas-Green, now a postdoc at the Massachusetts Institute of Technology who finished her Ph.D. in 2020. “Coulter BME has a reputation for recruiting and training fantastic students, and it’s great to see the Department welcoming back former trainees as faculty. I think it’s a testament to the strength of the education and research program.”

Interim Wallace H. Coulter Department Chair Machelle Pardue said making the early mutual commitment helps build the future

of the Department — and the field.

“We’re proud to welcome Simone to our faculty in the coming years, because we are confident about the impact she will have,” Pardue said.

“This early commitment allows us to invest in talented scholars and build

our next generation of innovative and impactful researchers.”

Douglas-Green’s dissertation research with Professor Manu Platt focused on cysteine cathepsins’ role in making or breaking fibrin, an essential blood-clotting protein and a biomaterial commonly used in tissue engineering. Her work examined both the abnormal blood clotting in sickle cell disease and remodeling engineered microvascular networks.

In her postdoctoral work, DouglasGreen is focused on drug-delivery via nanocarriers. She’s working to understand protein “coronas” — collections of proteins and other molecules in the body that can attach and become a thin film on the surface of nanoparticles when they come in contact with biological fluids.

Even before she returns to Coulter BME, Douglas-Green will have a team of mentors from the Department helping ensure her success and guiding her along the path to becoming an independent researcher. ‣ JOSHUA STEWART

Ting Appointed to McCamish Distinguished Chair Professor Lena Ting has been named the inaugural McCamish Foundation Distinguished Chair at Emory University, an endowed faculty position supported by a partnership between the Coulter Department and the McCamish Foundation.

The new endowed chair recognizes high-performing faculty members in Coulter BME working in areas related to Parkinson’s disease and whose work has great potential to impact treatment of the condition. It’s one of four endowed positions created through a transformational gift from the foundation in late 2020 that also established the McCamish Parkinson’s Disease Innovation Program.

“I am honored to be able to recognize Lena Ting as our inaugural McCamish Chair at Emory,” said Machelle Pardue, who served as interim Wallace H. Coulter Department Chair in 2021-22. “Her work on the neuromechanics of human balance and gait presents many exciting opportunities to transform our understanding 47

of how Parkinson’s impairs movement, and she will be an important part of our work with the foundation to develop revolutionary approaches to the disease.”

Appointment as the distinguished chair comes with discretionary funds to support student researchers, explore uncharted areas of research that could prompt external grants, and cultivate relationships with industry and research community leaders.

“The funding from the McCamish Foundation Distinguished Chair will allow us to more rapidly pursue novel approaches to probing and understanding brain-body interactions in healthy and impaired movement, including Parkinson’s disease,” Ting said. “With these resources, we can undertake impactful collaborative research fueled by our best students and postdocs being trained at the interface of neuroscience, biomechanics, engineering, and clinical research.” ‣ JOSHUA STEWART

Wallace H. Coulter Department of Biomedical Engineering

LEARN MORE ABOUT THE MCCAMISH PARKINSON'S DISEASE INNOVATION PROGRAM: parkinsons.gatech.edu

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FDA Clears the Way for Surgical Device Developed in MBID Program Eight years ago, a team of students in the Master of Biomedical Innovation and Development program tried to address a pressing need in sports medicine: how to treat millions of patients with chronic soft tissue injuries that would not respond to physical therapy.

Their solution was a microinvasive surgical tool called the Ocelot, developed during the one-year master’s program known as MBID in the Coulter Department. Soon, the Ocelot could be in the hands of physicians treating patients with chronic tendon pain.

TendoNova, the company the four former BME students started to commercialize their idea, announced in March 2022 that its Ocelot tool received U.S. Food and Drug Administration 510(k) clearance, allowing the company to begin marketing and selling the device.

“The MBID program played a pivotal role in our journey by providing us with the fundamental tools and frameworks to translate an unmet need into a viable commercial idea,” said Luka Grujic, TendoNova co-founder alongside fellow MBID grads Shawna Khouri, Brett Rogers, and Jonathan Shaw.

The Ocelot device is a handheld tool to perform mechanical fragmentation and debridement of targeted tissues, a common procedure for athletes and others suffering from tendon pain disorders like tennis elbow, plantar fasciitis, and jumper’s knee. More than 30 million people in the U.S. suffer from chronic tendon pain, and half of them have little or no relief. The fragmentation and debridement procedure encourages growth of healthy tendon to replace the painful tissue.

“The MBID program played a pivotal role in our journey by providing us with the fundamental tools and frameworks to translate an unmet need into a viable commercial idea.”

– LUKA GRUJIC

The first prototype of their device was basically a beefed-up tattoo gun.

Except, instead of an oscillating needle penetrating the top layer of skin with ink, this model went beneath the skin to reach the pathological tissue.

“We used inspiration from the tattoo gun’s human factor design to make the Ocelot usable with a single hand and a pencil grip, since both the tattoo gun and our device require precision and accuracy when being used,” Grujic said.

The team made modifications, such as adding a cannula around the oscillating component to protect surrounding tissue, making the device more tube-shaped for easier maneuverability inside the body, and lowering the noise with different hardware to reduce patient anxiety.

At the end of the MBID program, the team had a prototype that represented a vision of what the Ocelot device and TendoNova could become. MBID Program Director Sathya Gourisankar wasn’t surprised by the team’s rapid progress.

“They displayed enormous aptitude for innovation from the outset and made tremendous progress on identifying the relevant unmet clinical need, followed by concept phase development, and finalizing it to a viable bench to bedside prototype — all within three semesters of the MBID program,” Gourisankar said. ‣ JERRY GRILLO

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From Capstone Design to Published Research Intended as the “capstone” to students’ time in the Coulter Department, senior design projects often become presentations to outside groups, posters at professional conferences, or even fledgling startups.

Now, they’re also resulting in published research papers in academic journals.

Three Coulter BME Capstone Design teams published academic papers this year, a first for the program and the result of strong partnerships with clinicians and researchers at outside organizations.

THE CUMULATIVE EFFECTS OF LOW-LEVEL BLASTS The initial charge to Jessica McElrath, Brady Muñoz (née Bove), Jordyn Sak, Grace Trimpe, and Julia Woodall was broad: mitigate mild traumatic brain

injury (TBI) among Army Rangers. It wasn’t until they dug in and started talking to Rangers with TBI symptoms that they zeroed in on mortarmen.

“There are so many mortarmen who are talking about having headaches, memory issues, and all these different symptoms related to concussion and mild traumatic brain injury, yet there are very few who are actually diagnosed, let alone treated,” Sak said. “They don't have a blast event to account for those symptoms. And it became clear it's not one big blast event — they're exposed to hundreds of small blast events repeatedly over time, and that's contributing to a problem.”

The team combined data about symptoms reported by mortarmen with their pupils’ reflexive response to light, a recognized measure of changes in brain function. They also measured the actual pressure produced by firing the mortars.

Their findings, published in Military Medicine, suggested “a concerning health risk for mortarmen” and recommended “[b]ehavioral changes like ducking and standing farther from the mortar when firing” as well as daily safety thresholds and firing limits during training.

McElrath said one of the officers they worked with suggested their data could be useful in justifying changes to

training, such as switching to expensive mortar simulators that don’t produce the harmful blast overpressure. Sak suggested their data could help establish treatment options through the Veterans Administration health system for former mortarmen.

“There are a few other papers out there, not with mortar systems, but others that are starting to credit how cumulative blast exposure is really detrimental to brain health,” Woodall said. “We think this is adding to the wave of those papers that are really going to make a paradigm shift, hopefully, in how the military views preventative measures as a way to safeguard mortarmen and military service members’ health.”

PRACTICING BRAIN SURGERY OUTSIDE THE OR Brain function also was core to the work of Faith Colaguori, Rebecca Forry, Maité Marin-Mera, and Megan McDonnell.

Working with the Mayo Clinic, their charge was to develop a training device to help residents and trainees practice brain surgery techniques outside of the operating room. They 3D-printed a mold to create a patient-specific, anatomically accurate, and electrically

“There are a few other papers out there ... starting to credit how cumulative blast exposure is really detrimental to brain health. We think this is adding to the wave of those papers that are really going to make a paradigm shift in how the military views preventative measures as a way to safeguard mortarmen and military service members’ health.”

— JULIA WOODALL Five Coulter BME students worked with the 3rd Battalion, 75th Ranger Regiment at Fort Benning in Columbus, Georgia, to measure the effects of low-level blast exposures. (PHOTO COURTESY: PROJECT HALO) 49

Wallace H. Coulter Department of Biomedical Engineering

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From left: Faith Colaguori, Maité Marin-Mera, and Megan McDonnell of Team Brainy Bunch with their brain model.

(PHOTOS COURTESY: TEAM BRAINY BUNCH)

responsive brain model that simulates the mapping that surgeons do to identify functional brain areas during surgery.

In a study published in Operative Neurosurgery, the team and their co-authors called the model “the first of its kind as a functional anatomic model that allows stimulation of brain tracts not available in even the best cadaveric specimens.”

Though the idea was to help with training, it quickly became clear the tool could be useful for experienced neurosurgeons too, McDonnell said.

“As we went through the project, it also took on this role as a preoperative planning tool that could be used by neurosurgeons of any skill level,” she said. “The doctor could basically print out a version of the case that they're about to perform and use it as a practicing tool before they're operating on the live patient.”

The team built their proof-of-concept model using anonymized patient brain scans, and they embedded wires to simulate the electrical properties of brain tissue. As the team developed their model, they tested it with nearly three dozen surgeons, who told them it was key for the model to accurately mimic brain anatomy as well as the tactile and electrical stimulation feedback of surgery.

Nearly all of them found the model to be useful for training.

SEMIAUTOMATED SPINAL MEASUREMENTS MID-SURGERY For Yoel Alperin, Parth Gami, Sindhu Kannappan, and Kelly Qiu, helping with surgery was also a driving force. They created a way to quickly and accurately measure spinal alignment during surgery to correct scoliosis, without using radiation to collect images.

Instead, their device uses computer vision and a kind of machine learning known as deep learning to calculate two critical measurements, and they’ve documented the feasibility of their approach in the Journal of Neurosurgery: Spine with mentors from Mayo Clinic in Jacksonville.

The idea is to quickly and accurately give surgeons data on how well they have corrected the curvature of the patient’s spine without traditional radiographic tools. Usually that information would come via X-ray or CT scan in the operating room, with doctors pausing the procedure to acquire key metrics, like the Cobb angle and plumb line.

“There's currently not a convenient way to measure, intraoperatively, the alignment of the spine during scoliosis surgery,” said Kelly Qiu, a member of the team. “The current methods are radiographic; however, they take a long time, and

it also exposes the patient as well as the staff in the OR to a lot of radiation.”

The team’s system relies on custom 3D-printed markers placed at key locations on the spine during surgery.

An off-the-shelf camera captures an image, and a custom deep learning algorithm spots the markers and makes quick calculations for surgeons. Deep learning builds layers of algorithms in networks modeled on the human brain.

The team validated the system using a cadaver with scoliosis and reported the automated approach produced data well within clinically accepted parameters.

The study also noted the prototype device could cut time for intraoperative measurement from 15 minutes for a typical radiographic approach to roughly one minute. ‣ JOSHUA STEWART

Right: A prototype device built to quickly and accurately measure spinal alignment during surgery to correct scoliosis without using radiographic approaches. (PHOTO COURTESY: YOEL ALPERIN, PARTH GAMI, SINDHU KANNAPPAN, AND KELLY QIU)

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Krish Roy, Rafael Andino Take Top Georgia Bio Honors for Impact on Lifesciences Industry The Coulter Department was well represented at life sciences trade association Georgia Bio’s 2022 Golden Helix Awards.

The highest honor — the 2022 Industry Growth Award — went to Professor Krishnendu Roy and Rafael Andino, a member of the Coulter BME Advisory Board and instructor in the Master of Biomedical Innovation and Development program. The award recognizes two people each year who have made extraordinary contributions to the growth of the life sciences industry in Georgia.

Associate Professor James Dahlman also represented Coulter BME at the event, where Beam Therapeutics’ acquisition of his startup Guide Therapeutics was one of the Deals of the Year.

For Andino, who is Clearside Biomedical’s vice president of engineering and manufacturing and earned his undergraduate degree in mechanical engineering at Georgia Tech, the award is recognition of a career that began on the ground floor of a growing industry.

“I was probably one of the first graduate biomedical engineers that went to work in the biomedical industry in the late 1980s, and there’s been unlimited growth opportunity for the past 35 years,” Andino said.

He also found time to serve as an officer in the Air Force Reserve for the past 20 years, while helping to develop and launch dozens of medical products, technologies, and drugs that have benefitted patients around the world.

“To do it from right here in Atlanta has been unbelievable,” said Andino, who

Top to bottom: Roy, Andino, and Dahlman.

RACHEL EPPERSON, BME 2022 Statistically, Georgia Tech is a stellar choice, but it is much more than a school with a ranking or certification. BME at Georgia Tech is about the people. They are the most outstanding, well-rounded staff and students I have ever had the pleasure of interacting with. I chose BME for this exact reason: because it feels like home! My experience has far surpassed what I could’ve ever hoped or imagined.

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Wallace H. Coulter Department of Biomedical Engineering

also has worked in leadership positions for Bard Medical, and founded and led a company called Biofisica that developed technology to speed wound healing and regeneration of connective tissue.

In addition to his faculty role in Coulter BME and running a busy lab, Roy is director of the National Science Foundation Engineering Research Center for Cell Manufacturing Technologies (CMaT) and the Marcus Center for Cell-Therapy Characterization and Manufacturing (MC3M).

“I’m deeply humbled to receive this highest honor from Georgia Bio,” said Roy, Robert A. Milton Chair in Biomedical Engineering. “I think we’ve made tremendous progress in growing the biotech industry infrastructure in the state, and Georgia Bio’s leadership in transforming the biotech landscape has been instrumental.”

So has Roy’s. Through his leadership of both CMaT and the Marcus Center, he’s helped forge a strong industry-academia network, which he said has helped put Georgia “on the advanced therapies map for industry.

“We’ll continue to work to bring more biotech companies to Georgia and collaborate closely to accelerate research, development, and workforce training in partnership with Georgia Bio and other stakeholders,” he added.

Dahlman cofounded Guide Therapeutics in 2018 based on barcoding technology developed in his lab. The idea is to develop the tools for guiding gene therapies, using lipid nanoparticles. It’s a good enough idea that Beam Therapeutics paid $120 million up-front in an all-stock deal announced in February 2021. ‣ JERRY GRILLO

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Mitchell Lab Intern Publishes Study to Help Improve Alzheimer’s Clinical Trials Velda Wang started looking for opportunities to dig into the human brain the summer after her sophomore year at Parkview High School.

While taking an Advanced Placement biology class, she’d become interested in Alzheimer’s disease, discovered there wasn’t a cure or known cause, and decided she wanted to help change that.

She soon found her chance in the lab of Coulter BME Assistant Professor Cassie Mitchell.

“I wanted to get involved in research, delve deeper than I could in high school, and see if I could make an impact, even in a small way,” Wang said. And she did — Wang was co-lead author of a peer-reviewed academic paper published in the journal Brain Sciences,

the result of her work as a high-school intern in Mitchell’s research group.

In part, the paper describes how Wang designed an algorithm that could give researchers new avenues to pursue when probing why certain drugs or supplements give a person risk or resilience to Alzheimer’s.

Wang shared the lead author role for the study with fellow researcher Jayant Prakash. He graduated with his master’s degree in computer science while they were working on the study, leaving Wang to guide the project to completion alongside undergraduate research assistant Robert Quinn, the paper’s other co-author with Mitchell.

The research aimed to tackle a key issue with Alzheimer’s disease: Patients have vastly different attributes (like genetic backgrounds, lifestyles, or pre-existing conditions), onset age and symptoms, and progression patterns.

Those differences mean potential drugs might help specific sub-groups of patients but never make it through clinical trials because the effects

are diluted in the broad population of disease patients, Mitchell said.

The researchers used machine learning to “cluster” patient subpopulations. Prakash led that part of the project. Then they used a type of machine learning called association rule mining, or ARM, which examined the impact of drugs and supplements on different sub-populations. That was Wang’s part.

“She made the ARM algorithm for drug mining, then she had to map those drug patterns back to the subpopulation clusters Jayant found with his algorithms,” Mitchell said.

It’s exciting work, she said, because the sub-population clusters they identified will generalize to other Alzheimer’s patient populations, “and their attributes will help future trials have some guidance on how Alzheimer’s patients could be segregated to help find drugs that work for a least a portion of patients.”

‣ JERRY GRILLO

Paige Receives 2021 Staff Culture Champion Award For Kim Paige, the culture of the Coulter Department is at the root of everything.

Culture impacts the Department’s most critical asset — people — as well as the organization’s productivity, progress, and service.

In fact, she likens it to an ecosystem: a delicately balanced, intricately interconnected network grounded in a community of people working together toward a common goal. As she put it, “Respectful engagement across our diverse and unique contributions, collaboration, and connecting values, beliefs, and attitudes fuel our culture.”

If those relationships and contributions are fuel, then Paige is one of the catalysts that helps those elements ignite to form one of the nation’s most-respected biomedical engineering programs —

perhaps a key reason she won a 2021 Culture Champion Award from the Georgia Tech College of Engineering.

Paige, who works as the Department’s educational outreach manager and retention advisor, won the Culture Champion Award on the strength of nominations from colleagues. They highlighted her efforts to engage and connect staff and faculty members as well as her vision for uniting the entire Coulter Department.

“She has tirelessly worked to help create a departmental culture that is welcoming to, and supportive of, our diverse student body,” one nominator wrote.

“This takes a village to accomplish, [and] Kim has proactively engaged both faculty and staff to help with that mission.”

Kim Paige (right) with interim Chair Machelle Pardue.

‣ JOSHUA STEWART

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NSF Awards Prized Graduate Fellowships to 8 Coulter BME Students Applying for graduate fellowships from the National Science Foundation is a highstakes affair. Students only get one shot at one of the most sought-after grants for American graduate students. This year, the work paid off for seven Coulter BME graduate students and an undergrad about to embark on her Ph.D. studies.

They’re working to manufacture cells for the revolutionary CAR T cell cancer immunotherapy, developing synthetic immune organs in a dish or on a chip to understand and treat immune-related diseases, engineering stem cell therapies for patients with Duchenne muscular dystrophy, and much more. ‣ JOSHUA STEWART

ANJANA DISSANAYAKA

First-year Ph.D. student Advisor: David Myers

Research: “In working to engineer a solution for cerebrospinal fluid leakage detection, I have uncovered a new paradigm of hybrid polymer-paper based microfluidics. This innovative combination leverages the strengths of each modality (paper or polymer) and provides synergy as capillary wicking generated by paper devices can drive the polymer fluidic movement, which is superior at complex sample preparation. As a first application of this paradigm, I will create a device that can accurately identify CSF leaks using this novel polymer-paper approach.”

MARY KATE GALE

Fourth-year undergraduate Pursuing a Ph.D. in Bioengineering at Stanford University

neuroscience. I am interested in considering the brain in terms of its complex circuitry, and what patterns of neurons firing — either as individuals or synchronized groups — can tell us about how the brain operates. I don't know what particular brain region or application I want to apply that to, but left- versus right-handedness is a pet interest of mine.”

SHAYLYN GRIER

First-year Ph.D. student Advisor: Krishnendu Roy

Research: “The primary focus of my work pertains to the manufacturing of T cells for CAR T cell therapy. I primarily focus on optimizing the T cell activation and expansion process by identifying ways to increase the expansion yield and T cell persistence. I aim to influence these characteristics using metabolic programming and bioreactor design.

Ultimately, advancement in these areas will further improve the application of CAR T cell therapy so that it may be of benefit to a greater number of patients.”

Research: “I am pursuing computational

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Wallace H. Coulter Department of Biomedical Engineering

KENDREZE HOLLAND

Second-year Ph.D. student (Bioengineering) Advisor: John Blazeck

Research: “I engineer Cheerio-shaped DNA plasmids to guide inactivated Cas9 proteins to genes of interest in the model organism Saccharomyces cerevisiae with the goal of increasing and/or decreasing mRNA expression.”

VALERIA MONTSERRAT JUAREZ

Second-year Ph.D. student Advisor: Ankur Singh

Research: “My work focuses on bioengineering synthetic immune organs in a dish or on a chip. By developing these mini organs, I intend to study response to vaccines, infections, as well as changes to the gut microbiome. I hope this innovative research will lead to better understanding and treatment options for conditions influenced by altered immunity, such as inflammatory bowel diseases, aging, and infectious disease.”

C. ALESSANDRA LUNA

First-year Ph.D. student Advisor: David Myers

Research: “I am working on designing an ultrasound-based

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implantable pressure sensor for patients that rely on shunts to regulate their intracranial pressure (ICP). Diagnosing patients with shunt dysfunction is difficult because symptoms are non-specific — headache, nausea, or fatigue — and existing tests are costly, slow, or require invasive surgery.

Therefore, my role is to develop an ultrasound-based implanted sensor that can detect shunt failure by continuously and non-invasively measuring a patient's ICP and produces a quick, accurate, easily readable signal.”

NIA MYRIE

Second-year Ph.D. student Advisor: Andrés García

Research: “My research is motivated by a muscular disorder known as Duchenne muscular dystrophy (DMD). Muscle cells in DMD patients are missing a crucial protein called dystrophin. Without it, their muscles degenerate and become weak, and patients suffer from ambulatory disability and cardiorespiratory failure. My work involves engineering hydrogels to deliver healthy muscle stem cells to dystrophic diaphragm muscle. As a result, these cells can restore dystrophin, contribute to muscle regeneration, and improve function in the recipient’s muscle. With success, my work would support further research to optimize this platform for stem cell delivery to DMD patients suffering from respiratory failure.”

COREY ZHENG

First-year Ph.D. student Advisor: Shu Jia

Research: “Improving the capability of imaging systems through the development of new and unique kinds of lenses.”

Mira Mutnick Wins Goldwater Scholarship Third-year biomedical engineering student Mira Mutnick has been named a Goldwater Scholar for 2022, one of the nation’s most prestigious honors for undergraduates in science, math, and engineering.

Mutnick has been part of Coulter BME since she was a high school senior and worked as an intern in Cassie Mitchell’s lab. That was the beginning of a long line of research experiences that took Mutnick to other labs at Tech as well as the University of Houston and Tel Aviv University in Israel.

“I have had a lot of research experience as I narrowed down my particular field of interest, and I am so grateful for every opportunity I have had the honor of pursuing,” said Mutnick, whose work has included co-authoring a study published in 2021. She has worked in data science, tested wheelchair cushion performance, and helped develop customizable 3D-printed hand splints for children with cerebral palsy. Now she’s looking at doctorate programs, where being a Goldwater Scholar will help set her apart, she said.

The Barry Goldwater Scholarship and Excellence in Education Foundation selects scholars based on their potential to become the nation’s next generation of research

leaders. Mutnick wants to pursue a Ph.D. and a faculty position at a research university, driven by a desire to both represent and help people with disabilities.

Mutnick has a brittle-bone condition that means she uses crutches or a wheelchair sometimes to get around. After spending significant time in doctors’ offices as a child, she said, “I knew I wanted to help people in my disabled community, and that I loved math and science. I thought, ‘How cool would it be to make prosthetics?’ and that is when I discovered biomedical engineering.

“Oftentimes disabled people are the ‘patient’ or the ‘subject,’ not the engineer or the research partner.

While this lack of representation is a little discouraging, I recognize the role I can play by pursuing this field,” Mutnick said. “I can serve as a voice for the disabled community in accessible design and assistive technology, and as disability representation in STEM for others in my community — just as Dr. Mitchell was for me.”

Mutnick is the fifth Coulter Department student to win a Goldwater Scholarship since 2019.

‣ JOSHUA STEWART

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Student-Built PairMe Research Job Site Expands to All of Georgia Tech About a year after it debuted in Coulter BME, a platform to help undergraduate students find research opportunities and research mentors has expanded across Georgia Tech to students in all majors.

Undergraduate student Amy Liu created the site, called PairMe, in Fall 2021. Now she’s partnered with Tech’s Undergraduate Research Opportunities Program and the Undergraduate Research Ambassadors to broaden access. Which, truth be told, was what she had in mind all along.

“I quickly realized it would be a lot more feasible to start with a smaller group to conduct a pilot run and refine the process before expanding,” said Liu, who finished her bachelor’s degree in the spring. “It made perfect sense for me to start with my own

major, since BME has the highest undergraduate research participation rate across majors and we had the additional need for our researchers at Emory to recruit Georgia Tech students to their labs.”

PairMe connects students interested in a research experience with labs that have work and want to mentor undergraduates. Mentors post opportunities; students can apply for positions directly through the platform.

Liu knows the value of undergraduate research. Since her first year, she has worked on several projects in Coulter BME Professor Shu Takayama’s lab. Though she connected with Takayama’s research group fairly quickly, she saw the search didn’t always go as smoothly for some of her fellow students. She also found in talking to researchers that they were interested in ways to more actively recruit students.

“This expansion also opens up the potential for students to apply to labs outside their major, which is a key benefit for interdisciplinary projects that would otherwise be unable to reach a specific target audience,” Liu said.

“Sometimes what a BME project needs is a computer science student who will be able to complete a machine learning genetics project, for example.” ‣ JOSHUA STEWART

Grazia Marsico Selected for Curie Postdoc Fellowship Georgia Tech postdoctoral fellow Grazia Marsico has received a global fellowship from the Marie Skłodowska-Curie Actions, the European Commission’s flagship program for supporting top postdoctoral researchers.

Marsico has been working in Associate Professor Ankur Singh’s lab for about a year and a half. The Curie Postdoctoral Fellowship will allow her to continue her training in the Coulter Department for two years and support an additional year of study at the University of Tübingen in Germany.

“The Marie Curie Actions are the most prestigious research funding, and this fellowship gives me the opportunity to continue working in world-leading labs, with cutting-edge projects, and to unlock the path to an academic position,” said Marsico, who hails from Italy and earned her Ph.D. at National University of Ireland, Galway.

The postdoctoral fellows program supports excellent researchers working on an original research project, according to the European Commission, helping them develop their careers through international, interdisciplinary advanced training and experiences.

In Singh’s lab, Marsico has been focused on engineering lymphoma organoids that will mimic the tumor microenvironment and serve as a tool to design therapeutic strategies. After her postdoc studies, she said she hopes to return to Italy as a university faculty member and researcher.

‣ JOSHUA STEWART

OUR COMMUNITY

Nakatani Program Gives Japanese Students the Tech Experience Minori Murachi is a biomedical engineering student from Japan who dreams of helping humankind explore and colonize Mars.

But first she has to build a resumé of research here on Earth, and her recent involvement in the Nakatani Research and International Experience for Students in Coulter BME is helping give her a head start.

The Nakatani-Coulter BME partnership gave her a taste of in-depth, collaborative research with international partners, culminating with a symposium and competitive poster session. It also exposed her to new cultural experiences and valuable networking opportunities, inspiring her to think even more deeply about a career in space exploration.

“Presently, we can get to Mars in a month or two, but the stress on the human body on the return from Mars is a problem, because the gravity environment is different from that of the Earth, and the human body is damaged by the effects of radiation and muscle atrophy,” Murachi said. “This is just one exciting area that I could help find solutions for with like-minded people I’ve met through the Nakatani program.

There is a golden opportunity to explore myriad scenarios in cooperation with international engineers and scientists.”

Murachi is a first-year grad student at Doshisha University in Kyoto, where she’s studying materials science in

a biomechanics lab. She was one of 11 students from Japan in the Nakatani program in Spring 2022.

Launched in Fall 2019 as a student exchange, the Nakatani program was put on hold along with almost everything else during the Covid-19 pandemic.

So far, Japan has sent students to Georgia Tech, and Tech students soon will engage in research in Japan.

The program is designed as a research experience for undergraduates, but it’s also much more than that, according to Coulter BME Professor Shuichi Takayama, director of the Nakatani program at Georgia Tech: “The emphasis also is on creating some cultural experiences for these students visiting the U.S., and on making connections and collaborating.”

That’s where Nakatani mentors come in. They’re expected to fill multiple roles over the five- to six-week student exchange experience. In addition to teaching and fostering basic research skills, they also act as hosts and cultural tour guides, taking the students to family dinners, or barbecues at Stone Mountain, or hikes in Northeast Georgia.

For Luna Nguyen, a grad student in the School of Chemistry and Biochemistry, the challenge was balancing her role as a mentor to three different students: Nakatani participant Naka Ida plus two full-time Georgia Tech undergraduate students.

“I wanted to give my Nakatani student the best possible experience, to nurture her interests in science, so I invested a lot of my time discussing how to do research with the hope that she would see the beauty of logical thinking,” said Nguyen, who is originally from Hanoi, Vietnam, and remembered what it was like being an exchange student in the U.S. and Canada during her undergraduate years — including how she sometimes felt excluded.

“I encouraged Naka to ask questions, and I encouraged my other two Georgia Tech undergrads to share their knowledge with her,” Nguyen said.

It left a lasting impression on Ida, who came to Georgia Tech specifically hoping to make those kinds of connections.

“I wanted not only to study and absorb as much knowledge and as many skills as possible, but also to learn the philosophies of Georgia Tech researchers,” said Ida, who was finishing her bachelor’s degree when she was accepted to the program before the pandemic and now is a second-year grad student in organic chemistry at Japan’s Hokkaido University.

“I hoped to establish friendships with other Nakatani participants and other Georgia Tech students, to talk about our majors, our future dreams, our life plans — to build long lasting relationships that might lead to future collaborative research.” ‣ JERRY GRILLO

Right: Naka Ida (left) won the Nakatani poster competition, with help from her mentor, Luna Nguyen.

Far right: Minori Murachi works on an experiment with assistance from her mentor, PJ Jarquin.

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OUR COMMUNITY

Pediatric Technology Center Names Desai an Inaugural Peterson Professor Professor Jaydev Desai has been appointed to one of the new Peterson Professorships from the Children’s Healthcare of Atlanta Pediatric Technology Center at Georgia Tech.

Supported by the G.P. “Bud” Peterson and Valerie H. Peterson Faculty Endowment Fund, the professorships are designed to engage and empower leading researchers in a diverse range of disciplines and support pediatric research that interfaces with Children’s.

The Peterson name is no doubt familiar to many at Tech. During his decade as president of Georgia Tech, Bud Peterson helped facilitate and build the research partnership with the pediatric hospital.

“The progress we’ve seen working collaboratively across disciplines has been one of the most rewarding experiences of my life as an administrator,” said Peterson, who remains a Georgia Tech faculty member. “The clinicians at Children’s encounter a host of different healthcare needs and problems. We develop solutions.

These professorships help us map our solutions to their problems.”

Desai is professor and Carol Ann and David D. Flanagan Distinguished Faculty

Fellow in Coulter BME and an expert in medical robotics. He said the professorship is a great honor, recognizing his existing close collaborations with Children’s physicians. It’s also encouragement to tackle a range of challenges in pediatric robotics, an under-explored research area.

“We are actively working on developing a steerable robotic system for minimally invasive pediatric neurosurgery as well as a voice-activated robotic hand exoskeleton customized for patients with spinal cord injury,” said Desai, who is director of the Georgia Center for Medical Robotics and associate director of the Institute for Robotics and Intelligent Machines, both at Georgia Tech.

Desai said the resources from the Peterson Professorship will help support those projects and others — in interventional cardiology and cancer diagnosis, for example.

“This is a humbling honor for me.

One of the great motivators for my move to Georgia Tech a few years back was to work in pediatric robotics with Children’s,” Desai said. “It is also an exciting investment that will lead to more opportunities and potentially tangible results at the end of the day.” ‣ JERRY GRILLO

“We are actively working on developing a steerable robotic system for minimally invasive pediatric neurosurgery as well as a voice-activated robotic hand exoskeleton customized for patients with spinal cord injury.”

— JAYDEV DESAI

ISHA DIAMBOU, BME 2022 Being a first-generation college student, I have faced many challenges and sometimes felt out of place at Georgia Tech, but that has allowed me to become comfortable with the uncomfortable. Through the BME Department, I've been able to participate in undergraduate research, build medical device prototypes, intern with Boston Scientific, and so much more. It has been a long journey, but because of all the great experiences I’ve had, I have so much flexibility with the opportunities and career path I want to take after graduation.

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OUR COMMUNITY

New Faculty KELLY J. CROSS, Ph.D. Assistant Professor

SAURABH SINHA, Ph.D. Wallace H. Coulter Distinguished Chair; Professor Research “My research is in the area of bioinformatics. We are interested in developing new techniques for analysis of genomics data, building on concepts in computer science, machine learning, statistics and physics. We work with biologists to study problems related to animal development and behavior as well as human disease. Molecular biology is rapidly transforming to a quantitative field where large and new types of data present unprecedented opportunities to learn about biological phenomena and human health, but only if the appropriate analysis methods are used. This is what excites me about my research, as I feel we can make a big difference in an important field of research.”

Research “I am a datadriven, culturally responsive engineering education practitioner, researcher, and educational leader.

Most broadly, my research focuses on driving cultural change and making diversity, equity, and inclusion a priority in engineering. I develop innovative ways to broaden participation in engineering via strategies to sustain faculty engagement in promoting inclusive teaching practices and sparking the genius of students in engineering education. My teaching philosophy focuses on student-centered approaches such as problem-based learning and culturally relevant pedagogy. My complimentary professional activities promote inclusive excellence through collaboration.”

ANANT MADABHUSHI, Ph.D. Professor Research “My research focuses on developing and applying computerized imaging and artificial intelligence (AI) tools to help detect, diagnose, prognosticate, and predict therapeutic response and benefit for diseases like cancer. These approaches have involved multimodal and multi-scale based interrogation or routinely acquired data (e.g. digitized pathology images and radiographic scans like CT and MRI) to help identify patients and groups at risk for a variety of diseases, forecast health outcomes, choose and evaluate treatment responses, and ascertain progression of a disease.

“Our team has employed novel computer-aided diagnosis, pattern recognition, and image analysis tools for identifying interpretable imaging biomarkers to facilitate diagnosis and prognosis of cancer as well as cardiovascular, kidney, and eye disease. Our group also has been developing computational image and bioinformatic algorithms to correlate radiologic and pathologic image patterns with the molecular phenotype of the disease (radiogenomics) and ways of combining disease patterns on imaging scans with genomic/ proteomic data to create better predictors of risk stratification and treatment response.”

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OUR COMMUNITY

Faculty Awards & Honors Fellow Elections

HANJOONG JO

Fellow, American Association for the Advancement of Science

KRISH ROY

Fellow, Controlled Release Society

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SHELLA KEILHOLZ

Fellow, American Institute for Medical and Biological Engineering

ANKUR SINGH

Fellow, American Institute for Medical and Biological Engineering

Wallace H. Coulter Department of Biomedical Engineering

WILBUR LAM

Fellow, American Institute for Medical and Biological Engineering

JAMES STUBBS

Senior Member, National Academy of Inventors

MANU PLATT

Fellow, Biomedical Engineering Society

MAY WANG

Fellow, IEEE

OUR COMMUNITY

Other BME Faculty Awards & Honors DANA ABOUELNASR

Student Recognition of Excellence in Teaching: Semester Honor Roll (Fall 2021), Georgia Tech Center for Teaching and Learning JULIA BABENSEE

Clemson Award for Basic Research, Society for Biomaterials LAURA CHRISTIAN

Governor’s Teaching Fellow Student Recognition of Excellence in Teaching: Semester Honor Roll (Fall 2021), Georgia Tech Center for Teaching and Learning Student Recognition of Excellence in Teaching: Semester Honor Roll (Spring 2022), Georgia Tech Center for Teaching and Learning

EVA DYER

CIFAR Azrieli Global Scholar 2022-24 RUDY GLEASON

Student Recognition of Excellence in Teaching: Semester Honor Roll (Fall 2021), Georgia Tech Center for Teaching and Learning KARMELLA HAYNES

Appointed to the National Science Advisory Board for Biosecurity, National Institutes of Health MARTIN JACOBSON

Student Recognition of Excellence in Teaching: Annual CIOS Award, Georgia Tech Center for Teaching and Learning CHARLIE KEMP

AHMET COSKUN

Student Recognition of Excellence in Teaching: Annual CIOS Award, Georgia Tech Center for Teaching and Learning Student Recognition of Excellence in Teaching: Semester Honor Roll (Spring 2022), Georgia Tech Center for Teaching and Learning JAYDEV DESAI

2022 Senior Faculty Outstanding Undergraduate Research Mentor Award, Georgia Tech

Student Recognition of Excellence in Teaching: Semester Honor Roll (Fall 2021), Georgia Tech Center for Teaching and Learning CASSIE MITCHELL

2022 Junior Faculty Outstanding Undergraduate Research Mentor Award, Georgia Tech 2022 Outstanding Achievement in Advancing Diversity, Equity, and Inclusion in Research, Georgia Tech Student Recognition of Excellence in Teaching: Semester Honor Roll (Fall 2021), Georgia Tech Center for Teaching and Learning

MAYSAM NEZAFATI

Student Recognition of Excellence in Teaching: Semester Honor Roll (Spring 2022), Georgia Tech Center for Teaching and Learning JAMES RAINS

Student Recognition of Excellence in Teaching: Semester Honor Roll (Spring 2022), Georgia Tech Center for Teaching and Learning

JAMES STUBBS

Student Recognition of Excellence in Teaching: Semester Honor Roll (Spring 2022), Georgia Tech Center for Teaching and Learning

ANNABELLE SINGER

Derek Denny-Brown Young Neurological Scholars Award, American Neurological Association Gilbreth Lectureship, National Academy of Engineering Invited to the EU-US Frontiers of Engineering Symposium CTL/BP Junior Faculty Teaching Excellence Award, Georgia Tech Center for Teaching and Learning Outstanding Faculty Achievement in Research Award (Early Career), Georgia Tech College of Engineering ANKUR SINGH

Mid-Career Award, Society for Biomaterials

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BIOLOCITY

Biolocity GUIDING MEDICAL INNOVATION TO MARKET What is Biolocity?

Biolocity grew from the successful five-year pilot of the Coulter Translational Fund. The program uses an integrated approach to accelerate the development and commercialization of promising innovations from faculty members at Emory University and Georgia Tech. Biolocity provides a combination of funding, project management, and consulting resources to technologies, diagnostics, and therapies that address unmet clinical needs and have compelling commercial appeal.

The Biolocity approach encompasses three components: • Biolocity U – educational resources focused on life-science commercialization, including consultations, workshops, internships, and legal office hours.

• Biolocity Fund – more than $1.5 million in funding available each year to Emory and Georgia Tech innovations through a multistage, competitive application process.

• Biolocity Launch – active project management and formal coordination with the life-sciences commercialization ecosystem for Biolocity Fund awardees.

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Wallace H. Coulter Department of Biomedical Engineering

Our Process

Biolocity U Consultation Meetings, Legal Office Hours, Bench2Market Talks, Internship Training

Biolocity Fund

Biolocity Launch

Application and Pitch Workshops

Focus on "Killer Experiment"

Milestone Development

Active Project Management

Project Selection

Ecosystem Integration

BIOLOCITY

Completing the Team

Biolocity-Funded Projects

by Category 2015-PRESENT

Device, 32% Therapeutics, 30% Drug Delivery, 17%

Heard

Gerard

April Heard joined Biolocity as program and operations manager in spring 2022 followed in short order by a new associate director, Harry Gerard.

Heard provides program planning and implementation of Biolocity’s funding cycle activities and tracks project budgets, progress, and metrics. She brings more than 15 years of operational management experience to the program. Already, Heard has proved adept at helping project teams refine their story and relay it in a way that resonates with their target audiences.

Gerard provides leadership, operational planning, compliance, management, and supervision of activities associated with Lab2Launch, a new coworking laboratory space to promote innovation and entrepreneurship. He serves as a navigator, mentor, and advocate for faculty-based startups. Gerard holds a master's degree in biomedical sciences and is passionate about inclusive innovation.

Software/ Health IT, 15% Diagnostics, 4% Cell Manufacturing, 2%

Our 2022-23 Cohort ATHENA | Athena is an early-stage cell therapy company developing a mesothelin-specific chimeric antigen receptor (CAR) T cell product for the treatment of mesothelioma and other mesothelin expressing solid tumors. Principal Investigator: Crystal Paulos, Ph.D., Emory University BYSTRO BY REVXON | A search engine for your lifesciences data. Principal Investigator: Thomas Wingo, M.D., Emory University DEXAPATCH | Low-swelling, steroid-releasing, implantable hydrogel platform to reduce post-operative inflammation in tight surgical spaces. Principal Investigators: Andrés Garcia, Ph.D., Georgia Tech; Adam Klein, M.D., Daniel Refai, M.D., Stephen Linderman, M.D., Ph.D., Emory University

“Biolocity was incredibly helpful. This funding allowed us to scale up our lead molecule [and] collect critical de-risking data for our projects, guiding us on the types of experiments to perform and informing us on pharma partnerships and startup considerations.”

Eric Ortlund, Ph.D. PROFESSOR, EMORY DEPARTMENT OF BIOCHEMISTRY

MAGTRACK | MagTrack is a wearable alternative controller that simplifies power wheelchair driving and the control of digital devices for people living with tetraplegia. Principal Investigators: Nordine Sebhki, Ph.D., and Omer Inan, Ph.D., Georgia Tech ORALLY BIOAVAILABLE CXCR4 ANTAGONISTS FOR THE TREATMENT OF CANCER | Best-in-class orally bioavailable CXCR4 antagonists heat up solid tumors. Principal Investigators: Dennis Liotta, Ph.D., Eric Miller, Ph.D., Haydn Kissick, Ph.D., and John Petros, M.D., Emory University PROLYMPH NANO | Drug delivery technology unlocks new market opportunities by targeting the lymphatic system.

Principal Investigator: Susan Thomas, Ph.D., Georgia Tech

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BIOLOCITY

“[Biolocity] gave us the time we needed to do market research and to grow as entrepreneurs. ...

We also did key technical work that required intense focus and time, which ultimately led to the successful fabrication workflows we are developing now. Without Biolocity, we would not be where we are. Period.”

Mason Chilmonczyk, Ph.D. CO-FOUNDER AND CEO, ANDSON BIOTECH, INC.

Success Stories The U.S. Food and Drug Administration has granted 501(k) clearance to ANGIOCLOUD to begin marketing its cloud-based software for clinicians. The company’s platform enables 3D visualization and measurement of cerebral blood vessels to help neurologists with diagnosis and preoperative planning. The company, co-founded by Frank Tong in the Emory Department of Radiology & Imaging Sciences, was part of Biolocity’s first cohort in 2015-16. The underlying technology for AngioCloud’s service was developed at Emory by Tong, Leandro Gryngarten, Marina Piccinelli, and Alessandro Veneziani.

Famed startup accelerator Y Combinator invested in ANDSON BIOTECH in January 2022 as part of its W2022 batch. Andson helps pharmaceutical companies quickly, accurately detect and measure chemicals during their drug development and quality control processes.

Spun out of Georgia Tech by postdoctoral research Mason Chilmonczyk and Professor Andrei Fedorov, the company’s technology cuts traditional mass spectrometry time from hours or days to minutes.

Biolocity portfolio companies CELLFE and AGRITHERA presented their pitches at the Coulter Investment Forum in April 2022 alongside other early stage biotech companies. CellFE, funded by Biolocity in 2016, has developed a scalable, high-throughput microfluidic device for the efficient delivery of gene-editing molecules into cells. Agrithera is developing cannabidiol (CBD) prodrugs to treat epilepsy without the typical pharmacological drawbacks. The company was part of the 2021 Biolocity cohort.

Top: Mason Chilmonczyk in the lab. (PHOTO: ROB FELT) Middle: Cerebral blood vessels.

Bottom: CellFE high-throughput microfluidic technology (PHOTO COURTESY: CELLFE) 63

Wallace H. Coulter Department of Biomedical Engineering

BIOLOCITY

Meet Our Experts in Residence Biolocity taps the expertise of consultants across a wide range of disciplines to guide funded teams on project-specific needs. The Experts in Residence actively participate in project meetings within their specialty area, offering teams strategic insights to help leverage their commercialization potential.

Our experts consult on everything from business, strategy, and product development to legal and regulatory issues.

AS OF FY21-22

Our current experts include: KEYTON WEISSINGER | For more than two decades, Keyton Weissinger has been creating and growing technology companies. He founded Hoteltools, the first cloud-based hotel property management system, selling in 2001 to Radiant Systems, which is now owned by NCR. Then he joined Dialog Medical as vice president of technical operations and became vice president of innovation at Standard Register when it acquired Dialog, leading all healthcare technology product strategy until Standard Register’s own acquisition in 2018.

Weissinger most recently co-founded Copient Health. He’s also a mentor for healthcare startups at Tulsa Innovation Labs.

MANUEL KINGSLEY | An expert in medical technology evaluation and commercialization, Manuel Kingsley has worked for McKinsey & Company in mergers and acquisition and developing growth strategies.

His experience includes leadership roles in product development, new market assessment, strategy, operations, and mergers and acquisitions at Baxter Healthcare, Edwards Life Sciences, and CR Bard.

RIFAT “RIF” PAMUKCU, M.D. | Rifat “Rif” Pamukcu is CEO of Midway Pharmaceuticals and managing partner of RxMP Therapeutics and Mobius Innovations. With more than 110 academic publications and 150+ patents, Pamukcu is regularly featured in the popular media. As founder and chief science officer of Cell Pathways, he raised more than $140 million and took the company public on the NASDAQ exchange.

Pamukcu also serves on the boards of Atrin Pharmaceuticals and Midway Animal Health.

BRIAN WALSH | Brian Walsh has built a career as a global technology and medical industry executive with expertise in general management, operations, and marketing. He has demonstrated commercialization skills in a variety of healthcare technologies and applications, including urology, surgery, orthopedics, oncology, imaging, lasers, and software.

Walsh’s insight helps firms commercialize complex solutions to address unmet business, customer, and clinical needs.

62 projects funded

16.6x ROI leverage in follow-on funding

22

startups

2

licenses to industry

5

products on the market

“This program helped us turn our idea into an actual company with legs. It gave us the confidence to believe that we could really turn this into a successful product and company.”

1

acquisition

Yogi Patel, Ph.D. CO-FOUNDER AND CEO, FOCUSED CRYO, INC.

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BIOLOCITY

Arthan Bhatt

Nada Boualam

Grayson Goss

Melissa Cadena

Keno Ogelohwohor

Jonathan Chen

Cassandra Tom

Kyle Cowdrick

Reece Williams

Internship Program Develops A New Generation of Innovators Biolocity’s internship program is designed to develop aspiring health technology professionals’ ability to conduct in-depth market diligence for early stage technologies. Interns work with the Biolocity team over a six-month period to support Biolocity’s diligence process for funding proposals.

“Working with Biolocity ignited a desire to seriously consider branching out from my original short-term career goal of medtech research and development and consider positions in venture groups within academic medical centers and global medical device firms,” said Kyle Cowdrick, a Ph.D. student in the Coulter Department. “I think my background, now enhanced

by Biolocity, uniquely positions me to add a lot of value quickly to such a group internally as well as externally to faculty and student innovators or strategic partners.”

Since 2020, Biolocity has trained 23 interns from 10 departments across three campuses. The hands-on, immersive experience teaches them to validate unmet

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Wallace H. Coulter Department of Biomedical Engineering

clinical needs, identify and formulate technology value propositions, create interview guides and conduct primary market interviews, and perform top-down and bottom-up market sizing.

Interns also learn to assess competitive landscapes, determine strategic positioning for early stage technologies, and identify key risks of commercialization. Along the way, they hone their writing skills for a scientifically literate business audience, and they get to network with and learn from seasoned professionals, including the Biolocity Oversight Committee.

“Biolocity was an engaging way to meet other students with similar interests and goals and grow my network,” said Nada Boualam, an Emory health policy and management Ph.D. student. “I particularly enjoyed the pitch meeting and hearing how the board thought about what technologies to fund. The experience gave me a small taste of what an investing or tech commercialization career would look like.”

ADVISORY BOARD

The Coulter Department

Advisory Board RAFAEL V. ANDINO Vice President, Engineering & Manufacturing Clearside Biomedical, Inc. ME 1988 (Georgia Tech)

ROBERT F. KIRSCH, PH.D. Allen H. and Constance T. Ford Professor Chairman, Department of Biomedical Engineering Case Western Reserve University

SYLVIA BARTLEY, PH.D. Senior Global Director Medtronic

XAVIER LEFEBVRE, PH.D. Global Vice President Medtronic Core Clinical Solutions Medtronic Technical Fellow Ph.D. ChBE 1992

KELLY BOLDEN, M.D., FACS Medical Director Cultura Plastic Surgery ELIZABETH COSGRIFF-HERNANDEZ, PH.D. Professor, Cullen Trust for Higher Education Endowed Professorship Department of Biomedical Engineering University of Texas at Austin RYAN DAVIS Senior Strategic Account Manager Neocis, Inc. BME 2005 HEATHER HAYES, PH.D. Product Leader PerkinElmer Ph.D. BioE (BME) 2010 CHRISTOPHER HERMANN, M.D., PH.D. Advisory Board Chair Chief Executive Officer and Founder Clean Hands – Safe Hands BME 2006, Ph.D. BME 2011, MSME 2011 (Georgia Tech) M.D. 2019 (Emory) SHAWNA KHOURI Manager, Virtual Health Tulsa Innovation Labs BME 2012, MSBME 2014

JASON LITTEN, M.D. Medical Officer Chimeric Therapeutics M.D. 2002 (Emory) BRAD MILLER Vice President, Market Development & Head of Clinical Care Carecubes NBB 2001 (Emory) ANGELA GILL NELMS Chief Executive Officer Forge Fractional BME 2007 ANN SATERBAK, PH.D. Professor of the Practice Department of Biomedical Engineering Duke University SUE VAN Emeritus Member President & CEO Wallace H. Coulter Foundation

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This artificial “biohybrid” fish is made with commercially available human heart cells and swims by recreating the muscle contractions of a pumping heart. Published in Science, the system brings engineers closer to complex artificial pumps that could grow with young patients. It also provides a new platform for studying heart rhythm problems. Page 14.

Visit us online to stay in touch all year. bme.gatech.edu | bme.emory.edu And find us on social media @CoulterBME

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