Fall 2023 Magazine | Wallace H. Coulter Department of Biomedical Engineering

FALL 2023 MAGAZINE

COULTER BME ON TOP

Industry-Focused Curriculum and Research Innovation Elevate Graduate Programs To Highest Ranking EXPLORING GENOME’S DARK REGIONS

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DIGGING DEEP INTO COMPUTATIONAL NEUROSCIENCE

COULTER BME AT A GLANCE

Coulter BME by the Numbers #1 #1

#1

BME undergraduate program in the nation U.S. News & World Report, 2024 Best Colleges

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

1,224

undergrad students

423

graduate students

60% women

50% women

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

$53M+

59+

Annual Research Awards (FY23)

27%

underrepresented minorities

24%

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 Master of Biomedical Innovation and Development Georgia Tech M.S. in Biomedical Innovation and Development – Advanced Therapeutics Emory University Ph.D. in Biomedical Engineering Emory University & Georgia Tech Ph.D. in Biomedical Engineering Emory University, Georgia Tech, & Peking University

ESSY BEHRAVESH Director of Student Services PAUL J. BENKESER Senior Associate Chair MICHAEL DAVIS Associate Chair for Graduate Studies JAYDEV DESAI Associate Chair for Undergraduate Studies SCOTT HOLLISTER Associate Chair for Translational Research HANJOONG JO Associate Chair for Emory

M.D. / Ph.D. Emory University & Georgia Tech

MICHELLE LAPLACA Associate Chair for Faculty Development

Interdisciplinary Ph.D. programs Georgia Tech

JOE LE DOUX Executive Director of Training and Learning

• • • • •

Bioengineering Bioinformatics Computational Science and Engineering Machine Learning Robotics

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 2023 Magazine

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FROM THE CHAIR

Dear BME Community,

T

his fall marked the beginning of a new era for Coulter BME: It was the start of our first academic year as the No. 1 graduate and undergraduate program in the nation (as judged

by U.S. News & World Report)!

These No. 1 rankings reflect the hard work and dedication to excellence from our entire community — faculty, staff, and students. It is an indication of their never-ending quest for knowledge, and their commitment to improve human health through education, research, and innovation.

The fall semester has come to a close, but the opportunities for the academic year still feel fresh and vibrant, even as winter approaches; opportunities for our brilliant new students to begin the next exciting phase of their lives, opportunities for our returning students to step back into the momentum of their challenging academic careers, opportunities for our expansive (and expanding) research enterprise.

This year’s magazine offers a glimpse into some of the impressive work and accomplishments of the people who comprise our Coulter community. You’ll

see how they have turned opportunity into real-world solutions to some of the world’s pressing biomedical challenges.

You’ll read about the collaborative effort to address cancer disparities in people of African descent. You’ll meet researchers who are developing better mRNA therapies for a wide range of pulmonary diseases.

You’ll discover a growing community of investigators who are connecting the dots in brain architecture and function to create better treatments for disease and addiction, advanced robotics, and more human-centered artificial intelligence.

Some are using AI to battle cancer. Some are developing wearable technology to help farmworkers avoid heat stroke. And others are taking creative approaches in addressing Parkinson’s and Alzheimer’s.

All of this just scratches the surface.

We can’t possibly fit everything into one magazine. These are just some of our highlights, some of what thrills me as we continue building the next phase of our journey on two extraordinary campuses. I hope that this publication — these stories, these numbers, our energy — whets your appetite, and inspires you the way that I’m inspired. I could not be prouder of my community!

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 2023 MAGAZINE FEATURES

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Exploring Genome's Dark Regions TAsst. Prof. Karmella Haynes is leading a multi million dollar BSF grant to discover how the "dark matter" of the genome controls living systems.

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Digging Deep Into Computational Neuroscience Mathematical modeling and computer simiulations may be key to discovering the complexities of the human brain to find better treatment for disease and addiction.

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Coulter BME On Top With a first-time no. 1 ranking for grad programs in the nation, the Coulter Department is forging a path to develop the next leaders in the biotech industry.

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DEPARTMENTS 5

Our Research

31

Our Community

45

Commercialization

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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

Bacteria Can Discard Damage to Survive Antibiotic Treatment It’s the quiet bacteria that you’ve got to watch out for, the bacteria that can survive antibiotic treatments by forming dormant, drug-tolerant “persisters.” These persister bacteria can wake up after treatment and that’s when they make trouble, causing infections.

Persisters were first described about 80 years ago in some of the first studies of the antibiotic penicillin.

Later, it was discovered that these bacteria didn’t have genetic resistance to antibiotics — they basically go dormant, hibernating, essentially hiding from the treatment that has been designed to kill them.

How they wake up again has remained a mystery. But a team of Coulter BME researchers are working to solve it.

Along the way they’ve developed a better understanding of how bacteria can resist the therapeutic power of antibiotics, which could lead to more effective treatments down the road.

“These persisters don’t have the genes that can inactivate an antibiotic, but they still survive treatment,” said Kyle Allison whose lab published its work in the journal Molecular Systems Biology. “Persisters are thought to play a role in a lot of different kinds of chronic infections. We approached them like an engineering problem. Rather than trying to invent or discover a brand-new antibiotic, perhaps all we need to do is understand why these bacteria survive.”

Most studies of persisters focus on figuring out how they form. But Allison reasoned that the therapeutically interesting question is: How do they wake up or resuscitate from their dormant state?

“It’s a challenge to study this because these are rare cells, and bacterial cells are very small, so they’re hard to track and it’s hard to monitor their behaviors,” said Allison.

“So, we developed methods that can look at thousands of cells at high magnification over long periods of time. That enabled us to study resuscitation – the waking-up moment for these persister cells in a statistically rigorous way.”

Allison — whose partner in the study was lead author Xin Fang, a postdoc in his lab — said they expected the bacterial cells to wake up randomly, which would be consistent with past studies into the phenomenon. But the activity of individual persister bacteria cells had never

been verified. Through their close inspection, using single-cell time-lapse microscopy, Allison and Fang noticed that persisters wake up at an accelerated rate after antibiotic treatment.

“This led to some interesting questions,” Allison said. “Was the antibiotic having an effect on the dormant persisters? They were thought to hibernate, to be oblivious to the antibiotic. But we saw that the antibiotic does have an effect — the more antibiotic they get during treatment, the slower they are to wake back up. We were even able to show that there is some damage in the persisters from the antibiotic treatment, and many persisters actually appear to discard that damage.”

Basically, it looked as if some persisters were actually sacrificing themselves, allowing the group to wake up and develop colonies. The persisters seemed to be enabling their own survival by partitioning — allowing some to die off so the rest can survive.

And the researchers saw this behavior when they studied multiple, different pathogens (escherichia coli, salmonella enterica, pseudomonas aeruginosa, and klebsiella pneumoniae) that cause completely different types of infection and have different mechanisms for tolerating antibiotics.

“The fact that they all have this cellular partitioning when they wake up after antibiotic treatment was pretty surprising,” Allison said. “It indicates the possibility that this non-genetic mechanism allows bacteria to survive in patients.”

Allison has been interested in the subject of antibiotic resistance since he was in graduate school. While he can’t claim that this resuscitation phenomenon is widespread in patients, the fact that the researchers observed it happening in lab samples, and randomly chosen patient samples, “is probably pretty significant,” he said. “It hints strongly that this may be an important mechanism underlying treatment failure in bacteria that lack genetic resistance.”

The exploratory and unique nature of the research was made possible by an NIH Director’s Early Independence Award, which grants flexibility to junior scientists like Allison pursuing high-risk research. ‣ JERRY GRILLO

Allison

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OUR RESEARCH

Blue Sky Grants Break With Tradition “Blue Sky” seed grants from the McCamish Parkinson’s Disease Innovation Program, as in the past, support research teams at Georgia Tech and Emory University who take a technology-driven approach in addressing the devastating brain disorder. But the 2022-2023 cohort of researchers is breaking with tradition.

“We’re starting to see more proposed projects from teams who have not traditionally worked in Parkinson’s disease,” said Garrett Stanley, professor and founding director of the McCamish program in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory.

“This is one of the goals of the McCamish Program, to help scientists and engineers who have worked in other areas bring their ideas and talent to understanding, treating, and one day curing Parkinson’s disease,” Stanley added.

The five new research teams bring a broad range of expertise for projects focused on robotics, wearables, assistive communication technology, and advanced personalized therapeutics. Grants were awarded in two categories: $40,000 for two teams engaged in earlier-stage research and $125,000 for three teams.

A team led by Coulter BME Associate Professor is using a $125,000 award to combine the concepts of fun and utility.

They’re developing a therapeutic robotic game system to increase and enhance the patient exercise experience, while reducing the demands on therapists. The goal is a future where people with Parkinson’s disease can play therapeutic games at home with interactive robots, giving therapists more time to provide individualized guidance.

Meanwhile, robotics researcher Yue Chen has a completely different aim in mind. He’s leading a team of engineers, scientists, and clinicians in developing, “a safer and more accurate approach for deep brain stimulation electrode placement during Parkinson’s disease treatment,” he said. Chen, an assistant professor in Coulter BME, is leading a team that received one of the larger grants.

“The Blue Sky grant will allow us to develop collaborations with the surgeons, identify the critical gap, and collect the preliminary data for future external grant applications,” Chen said.

Emory’s Amanda Gillespie, director of Speech Pathology in the Emory Voice Center, is leading a team that received a $125,000 grant to design the Speech-Assisting Multi-Microphone System (SAMMS) — wearable technology that can isolate, monitor, and

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Wallace H. Coulter Department of Biomedical Engineering

“We’re starting to see more proposed projects from teams who have not traditionally worked in Parkinson’s disease. This is one of the goals of the McCamish Program, to help scientists and engineers who have worked in other areas bring their ideas and talent to understanding, treating, and one day curing Parkinson’s disease.”

— GARRETT STANLEY

analyze vocal loudness and provide biofeedback to the wearer when minimum loudness targets aren’t met.

Minoru Shinohara, associate professor in Georgia Tech’s School of Biological Sciences, is leading a $40,000 early effort in wearable tech. Shinohara’s project aims to treat motor symptoms — like tremors, rigidity, and poor balance — with an on-skin, wireless system that automatically assesses dance therapy motions, with the aim of improving lower-limb motor control.

“Long term, we’d like to apply this approach to various rehabilitation exercises and clinical populations,” Shinohara said.

And Michael Borich, who runs the Neural Plasticity Research Lab at Emory, is leading a team leveraging its $40,000 award to begin preliminary work on improving mobility and reducing falls in Parkinson’s patients.

“The long-term goal of our project is to develop personalized, non-invasive brain stimulation techniques targeting abnormal cognitive-motor interactions,” Borich said.

The Blue Sky seed grant program, made possible by a gift from the McCamish Foundation, launched last year to identify and support engineers and scientists at Georgia Tech and Emory who can bring innovative approaches to Parkinson’s research.

“We are building a community of researchers across Georgia Tech and Emory that expands on what was already a strong effort in the Atlanta area,” Stanley said. “In future years, our goal will be to work towards narrowing the scope to focus on a coordinated effort across multiple teams, which is really unique and exciting.” ‣ JERRY GRILLO

OUR RESEARCH

Neural Clock May Synchronize Visual Behavior About half of the brain is devoted in some way to vision.

Our eyes observe the visual field, and that information is sent to the back of the brain, where it is processed. Then, almost instantaneously, we recognize the objects in front us. And we can shake the hand of an approaching friend, or we can move out of the way of oncoming traffic.

It’s lot to take in. All that precise recognition in a single glance takes an enormous amount of computation and synchronization. Driving this activity are neurons firing and communicating across the vast space between our ears so we can focus quickly and reliably on the right features. How all this complicated collaboration comes together is not entirely understood.

But a team of Georgia Tech researchers working to solve the mystery has discovered an internal “clock” that timestamps and synchronizes visual computation across different areas of the brain. The results of their studies help explain the remarkable precision of visual processing in a healthy brain.

Their findings also suggest new ways to think about brain activity when visual perception is neurologically impaired.

“It’s like what happens in a computer chip,” said Assistant Professor Bilal Haider. “All the instructions from open apps and software have to flow in a precise sequence so messages don’t get scrambled – and so your apps don’t crash!”

Electrified silicon chips are super-fast, so in a computer, the clock stamps and runs instructions millions of times a second. Haider and his team found that the visual processing clock, made of wet, squishy neurons, does pretty good, too.

“We found that the visual system runs instructions 60 times a second and makes sure each cycle of the clock is precisely timed across multiple visual regions of the brain,” Haider said. “We suspect that desynchronizing this clock could potentially underlie all sorts of visual processing deficits, which could mean scrambled, jumbled visual messages.”

Neurons work well together when one group sends a message, and the other group stands ready to receive it. Rhythmic brain oscillations are thought to play a key role in this process of communication and computation.

EEG-based neural oscillations are often observed in neurological diseases, noted Donghoon Shin, lead author of the research, published in the journal Neuron. “The specific function of neural oscillations remains an open question,”

he said. “Our paper provides a fascinating example at the intersection of neural oscillation, cooperation between brain areas, temporal coding, and visual perception.”

Shin, who was a graduate student in the Haider lab during the research, led the examination of narrowband gamma (NBG) oscillation, focusing on the relationship between oscillation timing and visual function. Oscillations occur at different frequencies in the brain, with higher frequency gamma oscillations controlling communication between different regions of the brain.

Previous studies of the visual system have proposed that broadband gamma oscillations facilitate brain-wide signal coordination underlying visual perception.

But the broadband frequency between different brain areas varies widely and doesn’t seem to provide the precise synchronization needed for optimum neural activity. Shin, Haider, and team performed new experiments that demonstrate how NBG oscillations can propagate and synchronize throughout an awake brain’s visual system with great precision.

The consistent rate of NBG oscillations (between 55 to 65 times per second, versus 30 to 80 times for broadband gamma) makes it easier for different brain areas to sync up, Shin said.

“More broadly, NBG oscillations across brain areas might be a way to ‘pay attention’ to the right features or locations for effective visual behavior,” Haider said. “So, a next step in the research would be to test the NBG clock, to see how it might be altered in neurological conditions where visual behavior is impaired and try to figure out if we need to ‘reset’ the visual clock to help improve behavior or attention.” ‣ JERRY GRILLO

BME researchers Donghoon Shin, left, and Bilal Haider.

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OUR RESEARCH

Closing the Loop to Target Brain Glioblastomas “Closing the loop” has become one of the jargony cliches of the business world. But in the world of cancer immunotherapy, closing the loop could be an innovation that unlocks powerful therapies for hard-to-treat brain cancers called glioblastomas.

Researchers at Georgia Tech and Emory University have developed a system that uses ultrasound-induced microbubbles to help a powerful immunotherapy target brain tumors and a custom algorithm to continuously fine tune the bubbles for maximum impact.

Their closed loop controlled focused ultrasound system proved effective in boosting survival rates in mouse models, including eradicating the entire tumor in at least one case. They described their approach in the journal Science Advances.

“With closed loop focused ultrasound, we observed statistically significant improved anti-PD-1 delivery, which is the antibody that we use for our immunotherapy. We also have observed improved efficacy of the combined treatment in a survival study,” said Hohyun “Henry” Lee, a Ph.D. student in the George W. Woodruff School of Mechanical Engineering, first author of the paper. “Recent studies have shown that focused ultrasound combined with microbubbles can enhance this immunotherapy technology. We developed

an algorithm that controls the focused ultrasound to maximize the combined effect of these two technologies.”

PD-1 is a key protein on the immune system’s T cells that serves as an off-switch, preventing T cells from attacking normal, healthy cells by mistake. However, sometimes PD-1 stops T cells from targeting cancer cells.

Left unbothered by the body’s immune system, those cells then can proliferate.

Anti-PD-1 drugs block the protein from shutting down T cells, freeing them to attack tumors. They’ve become a powerful weapon, particularly against melanoma and some lung cancers, but their effectiveness against brain tumors has been disappointing — partly because delivering drugs through the blood-brain barrier is a major challenge.

The system Lee developed with Associate Professor Costas Arvanitis is designed to get the anti-PD-1 therapy across the blood-brain barrier and into the tumor microenvironment using tiny bubbles one-thousandth of a millimeter in diameter. The focused ultrasound causes the bubbles to oscillate, which forces open the blood-brain barrier so the therapeutic agent can reach the tumor.

The researchers’ key innovation in this study is an algorithm that constantly measures the echoes of the bubbles to maintain optimum force while tracking

the bubble concentration and not damaging blood vessels. That’s the closed loop: The algorithm takes in a constant flow of data about the microbubbles and adjusts accordingly. Other microbubble systems lack this level of control.

“We need to really tune this pressure or force that we apply to these bubbles with ultrasound at a very, very high level of precision, and that's what Henry did,” said Arvanitis, who is jointly appointed in the Coulter Department and the Woodruff School. “If we have a lower vibration, we will not have the desired effect. If we have a higher level, we might create damage. It's really about tuning these micro- to nanoscale changes in the bubble radius and doing it completely noninvasively.”

Researchers created a focused ultrasound system that uses microbubbles to open a pathway for an anti-PD-1 immunotherapy drug to reach brain tumors. They designed an algorithm that takes in a constant flow of data about the microbubbles and adjusts accordingly for optimal impact. Other microbubble systems lack this level of control.

The adaptiveness of the team’s system results in a greater safety profile and the ability to fine-tune therapies for any potential patient. The algorithm detected signals that indicated trouble and adjusted accordingly, sustaining just-right microbubble oscillations in a dynamic environment where the line between stability and violent bubble collapse is whisper thin.

“Closing the loop and tracking the bubble kinetics in real time is critical for this research and moving to the clinic, where every time you have a new patient and a new case,” Arvanitis said. “When we talk to our colleagues in the clinic, they tell us that you have so many constraints, and you really need to be in position to make quick decisions without compro-

A rendering of the closed loop controlled focused ultrasound system.

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Wallace H. Coulter Department of Biomedical Engineering

OUR RESEARCH

mising safety and efficacy. That's what this controller would be able to offer.”

Other contributors to the paper included Woodruff School Professor F. Levent Degertekin, Postdoctoral Fellow Yutong Guo, Postdoctoral Fellow James L. Ross in the Emory Department of Microbiology and Immunology, and Scott Schoen from Massachusetts General Hospital.

Arvanitis said though they focused on developing the algorithm-controlled approach for brain cancer immunotherapy, it holds promise for enhancing delivery of therapeutics for other kinds of brain diseases too, like Alzheimer’s or Parkinson’s.

“Because it's so safe, it gives you the opportunity to treat multiple times and do treatment over a longer period. That could be key for neurodegenerative diseases,” he said.

For now, the team has demonstrated the system in small animal models, but they said their approach is easily scaled up to work with existing clinical systems. They hope to work with collaborators to include their approach in ongoing early clinical trials where they could further test safety and efficacy for human patients.

"We will continue advancing the method and instrumentation in the coming years to make this approach more effective and potentially more broadly applicable,” Degertekin said.

‣ JOSHUA STEWART

Top: Associate Professor Costas Arvanitis and mechanical engineering Ph.D. student Hohyun "Henry" Lee with their closed-loop controlled focused ultrasound system. The system uses ultrasound-induced microbubbles to help a powerful immunotherapy target brain tumors and a custom algorithm to continuously fine tune the bubbles for maximum impact.

Researchers created a focused ultrasound system that uses microbubbles to open a pathway for an anti-PD-1 immunotherapy drug to reach brain tumors. They designed an algorithm that takes in a constant flow of data about the microbubbles and adjusts accordingly for optimal impact.

Other microbubble systems lack this level of control.

(PHOTOS: CANDLER HOBBS)

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OUR RESEARCH

Healing Breath: Researchers Dramatically Upgrade Inhalable mRNA Therapy Messenger RNA, or mRNA, has been used to immunize millions of people in just the past few years, leading the world out of a pandemic, and allowing researchers to consider other therapeutic targets for these flexible, effective drugs.

Among the most likely targets for future mRNA therapies are the lungs, given the large number of pulmonary diseases, such as the coronavirus, influenza, asthma, cystic fibrosis, and others.

Now a team of multi-disciplinary investigators from five universities, led

by Georgia Tech faculty researchers, has provided a potential path toward that future. In a study published in November 2022 in the journal Nature Materials, they describe nanoparticle formulations designed specifically for inhalable mRNA delivery, via an easy-to-use nebulizer.

“Nanoparticles made of polymers have specific strengths, and the lung happens to be a place where they are very good for delivery,” said Phil Santangelo, Coulter BME professor.

In previous work, Santangelo’s lab also has developed mRNA payloads transported by lipid nanoparticles. But polymeric nanoparticles which are designed to carry drugs to their destinations have a higher loading capacity and are compatible with many compounds.

“In the lung, they’re just flat out better,” Santangelo added. “And we can use them with a wider range of nebulizers. That may not be as important for testing in rodents, but it is when you’re talking about getting this into a person.”

Polymers are large molecules comprised of small, repeating molecular building blocks called monomers. For this study, the researchers focused on synthetic, biodegradable polymers called PBAEs. In an earlier study, Santangelo’s team demonstrated the strength of PBAE formulations in delivering mRNA that can express the CRISPR Cas13a protein in lung tissue, where it was effective in stopping SARS-CoV-2 (coronavirus).

For the Nature Materials study, the researchers used a process called combinatorial synthesis — a method for preparing large numbers of chemical compounds — to screen 166 different PBAE formulations. One of these, P76, emerged as the best candidate for protein expression, that is, delivering the therapeutic goods efficiently into the lungs of animals, from mice to non-human primates.

That makes P76 species agnostic.

Turns out, the polymer is also compatible with a variety and combination of cargos, which is not typically the case in the delivery of RNAs.

But P76 has demonstrated its ability to transport disparate RNAs. So, in addition to being species agnostic, the polymer is mostly cargo agnostic, too.

“With this new polymer, compared to the old one from our previous work, we get much better protein expression,” Santangelo said. “We can actually decrease dosage by a factor of four, or 400%, and have the same therapeutic effectiveness.

That is a striking improvement.”

Santangelo’s lab collaborated with two Georgia Tech faculty members from the School of Chemistry and Biochemistry – Professor M.G. Finn and Associate Professor James Gumbart. The University of Georgia, University of Louisiana-Lafayette, and Mississippi State University were also part of the study, which involved more than 25 authors.

Their work in Nature Materials was published on the heels of another nebulizer-based study from the Santangelo team that was published in the journal Advanced Science. That work detailed the development of a more efficient, inhalable mRNA medicine to prevent respiratory virus infections like the coronavirus.

In both papers, which were supported by the Defense Advanced Research Projects Agency (DARPA), the researchers demonstrated the utility of polymeric formulations for delivering the potent cargo into the lungs.

“With these studies we basically wanted to make people aware of new versions of a class of molecules that have lots of advantages over the old ones,” Santangelo said. “And the reality is, I think, for the nebulization and delivery to the lung, they have big advantages.

These polymers make a lot of sense.”

And potentially, a lot of cents, too, with the global mRNA therapeutics market expected to exceed $26 billion by 2028. ‣ JERRY GRILLO

Researchers Daryll Vanover and Phil Santangelo.

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Wallace H. Coulter Department of Biomedical Engineering

$2.46 Million to Develop Intelligent Tools for Assessing Heat Exposure Effects The National Institute of Environmental Health Sciences awarded a $2.46 million grant to Emory University and Georgia Institute of Technology researchers to develop a multi-sensor biopatch for farmworkers that can predict symptoms of heat-related illness, dehydration, and acute kidney injury.

The four-year grant allows the team to develop a wearable wireless unit for farmworkers with sensors that can integrate key physiological signals, predict adverse heat-related medical events, and generate warnings about them in real time.

“When you think about people who work outside all day, and that includes construction workers and landscapers as well as farm workers and others, they are exposing themselves to potentially dangerous heat-related conditions,” said W. Hong Yeo, an associate professor in mechanical and biomedical engineering at Georgia Tech. He is leading development of the biopatch.

The findings of the project will lead to an intervention study in which data are sent from the biopatch to an Android device. The team will develop artificial intelligence (AI) tools for predicting study outcomes. In future research, the team envisions that data sent to the Android from the biopatch will be processed with these tools. After processing, warnings may be sent to workers from the Android device as necessary, which will help determine if the technology can reduce morbidity associated with occupational heat exposure.

Escalating trends of increasing environmental temperatures place

The stretchable electronics make the biopatch more reliable than conventional wearable devices. (PHOTO COURTESY: W. HONG YEO)

marginalized populations, such as agricultural workers who have routine occupational exposure to hot, humid environments, at increased risk for the acute health effects of heat exposure, according to Vicki Hertzberg, lead principal investigator on the project and a professor at the Emory University Nell Hodgson Woodruff School of Nursing.

“Heat-related illness and dehydration are particularly insidious, as they can quickly progress from moderate discomfort to confusion and impaired judgment, thereby diminishing the affected worker’s ability to seek necessary medical attention,” she said. “A hand-held device with clear information about heat illness will help farmworkers know when to seek help.”

Joining Hertzberg and Yeo as a principal investigator is Li Xiong, a Samuel Candler Dobbs professor in the Emory Department of Computer Science.

“We know that once we can get continuous physiological data in real time, then we can prevent this problem,”

said Yeo, a Woodruff Faculty Fellow who also is director of the Georgia Tech IEN Center for Human-Centric Interfaces and Engineering. “Currently, it’s very hard to measure real-time events because of the limitations of existing sensor or device technology.”

Conventional wearable devices tend to be rigid, heavy, and bulky – not useful for workers who spend a lot of time moving around.

“All of that motion means we’re losing data, so we’re creating a reliable solution,” said Yeo, whose lab specializes in the development of soft, wearable health monitors that use stretchable electronics.

Emory School of Nursing assistant professor Roxana Chicas leads the field team assessing the use of the biopatch on outdoor workers, and Jeff Sands, professor in the Emory Department of Medicine, will provide renal expertise. Completing the team is Nezahualcoyotl Xiuhtecutli, executive director of the Farmworker Association of Florida. ‣ MELANIE KIEVE Fall 2023 Magazine

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OUR RESEARCH

Hollister Lab Develops Blueprint for 3D Medical Devices There are young children today who are celebrating birthdays and holidays with their families because of the work going on in the lab of Coulter BME researcher Scott Hollister. His Tissue Engineering and Mechanics Lab, in collaboration in with the Global Center for Medical Innovation at Georgia Tech, is helping to lead a medical device revolution with the development of 3D-printed, implantable patient-specific devices.

These tracheal and bronchial splints have been used to treat children born with rare conditions, such as tracheobronchomalacia (airway collapse) or tracheal agenesis (a completely absent airway). Collaborating with clinicians who receive emergency clearance from the U.S. Food and Drug Administration (FDA) to use these devices, Hollister’s team is creating life-saving options for little patients who typically don’t have any.

Breakthroughs in 3D printing technology have enabled cutting edge academic research enterprises, like Hollister’s lab as well as traditional medical device companies and others to develop highly personalized devices.

All of which raises an important question: How do you guarantee safety and quality control, especially for patient-specific devices produced in small custom batches?

The Hollister lab has an answer for that, too, and it was

BME researchers Sriharsha Ramaraju and Scott Hollister. (PHOTO: ADAM VERGA)

More than a how-to guide, the Hollister team has created a how-to-do-it-properly script for developing medical devices through 3D printing, which is known as additive manufacturing — the process uses computer-assisted design and 3D object scanners, which direct hardware to deposit material, layer upon layer, to rapidly create a prototype or product.

It’s still an emerging technology in the medical device world, so the rules and regulations are evolving with the use of the technology. In 2017, the FDA released its guidance of the device manufacturing process.

“There is a lot of interest in additive manufacturing, and in regulating how devices manufactured through 3D printing could have the same kind of quality verification process as traditional medical devices,” said Harsha Ramaraju, lead architect of the framework and lead author of the Biomaterials paper. “So, we’ve developed a kind of reference manual, a generalized framework for creating custom devices.”

Since the FDA guidance was released in 2017, this is the first publication to describe the implementation of Good Manufacturing Practice (GMP) methodology for the 3D printing of custom patient specific devices. This framework was used to create devices for a 2018 patient case at Children’s Healthcare of Atlanta and the paper describes how devices were designed, manufactured, verified, and validated.

The Hollister lab focuses its attention on a process known as laser “We see this work as becoming a template sintering — laser is used as the heat for groups that want to create devices source on powdered material, binding it together to create a solid structure. for individual patients — ensuring safety “The unique aspect of this work is that and quality for devices that are not mass it can be adapted for a lot of other types of produced or tested on a large scale.” additive manufacturing,” Ramaraju said.

The steps Hollister’s team followed — SCOTT HOLLISTER in developing its devices — acquiring patient data, design verification, materials verification, parts manufacturing, device published in the October edition of the journal Biomaterials. evaluation — are the same general steps any other team “We see this work as becoming a template for groups that would need to take in high-quality 3D printed devices. want to create devices for individual patients — ensuring “Adhering to FDA guidance and implementing a GMP safety and quality for devices that are not mass produced process can only improve the overall quality of a device,” or tested on a large scale,” said Hollister, professor Ramaraju said. “And going forward, it creates avenues in the Wallace H. Coulter Department of Biomedical for broader use following more traditional pathways Engineering at Georgia Tech and Emory University. for medical devices in the future.” ‣ JERRY GRILLO

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Wallace H. Coulter Department of Biomedical Engineering

OUR RESEARCH

BME Researchers Partner with Morehouse School of Medicine to Probe Kidney Disease About 15% of the U.S. population — some 37 million people — in other areas as well, where apical access is required.” live with chronic kidney disease. But most of them don’t know There haven’t been many organoid-based studies they have it until the disease progresses to a later, serious of proteinuria, “because you need apical access,” stage. That’s because early on, there are few, if any, symptoms.

Parigoris said. “That’s where the uptake of protein “Another big challenge is, even though kidney disease happens, and that’s what we want to study.” is so prevalent, it remains an understudied problem,” said Tubuloids are specifically organoids for studying the kidney. biomedical engineer Eric Parigoris, a former Georgia Grown from donor kidney cells, tubuloids are made from cells Tech Ph.D. student who is working to change that. that compose the nephron. Each kidney is made up of about A primary factor of kidney disease is proteinuria, or high a million multicellular filtering units called nephrons, and levels of protein in the urine. It can be caused by temporary every nephron contains a long tubule. Hence, tubuloids. conditions like dehydration, intense exercise, or more These inside-out organoids come with a bonus — long serious problems, like diabetes, hypertension, chronic kidney life. That is, the tubuloids are produced and maintained disease, or a kidney disorder called nephrotic syndrome. in hanging drop cultures for more than 90 days, which Parigoris and his colleagues in the lab of BME Professor allows researchers to closely observe a chronic condition, Shuichi Takayama, in collaboration with the Morehouse Parigoris said. “The idea is, we would be able to expose School of Medicine, have developed a new 3D model for the organoid to, say, a high protein level for 90 days, or a studying proteinuric kidney disease: geometrically inverted particular drug for 90 days, and study what happens.” proximal tubule organoids. These ‘tubuloids’ are an improveGoing forward, Parigoris sees great potential for ment on current in vitro methods while avoiding the cost the organoid technology developed in Takayama’s and ethical concerns associated with animal studies. lab. For example, he said, these inside-out tubuloids Organoids are artificially grown, simplified, mini versions could be very useful in nephrotoxicity testing. of an organ produced in vitro, typically from donor stem “We know that certain antibiotics and chemotherapy drugs cells. These complex, self-organized collections of cells are known to be toxic to the kidneys,” said Parigoris, who used can recapitulate the processes of a patient’s own tissues, to volunteer at the Winship Cancer Institute of Emory, assisting making organoids powerful tools for studying drug interpatients undergoing chemotherapy. “Some of these drugs have action as well as tissue function and development. They been implicated with apical uptake. So that is a likely future represent a novel approach to personalized medicine. direction for these inside-out tubuloid studies.” ‣ JERRY GRILLO Previously, Parigoris and his collaborators developed geometrically inverted organoids for studying breast cancer That is, they made inside out organoids — the basolateral (exterior) and apical (interior) sides are reversed.

“The side of the cells that is exposed to proteins typically is on the interior of the organoid, the apical side, and you can’t access it,” said Parigoris. “So, when we flip these organoids, turn them inside out, that opens up the receptor that takes up protein, making it possible for us to study that process.”

Studying and modeling proteinuric kidney disease meant finding new collaborators. The Takayama team found theirs at the Morehouse School of Medicine in collaboration with Xueying Zhao. Much of her research has focused on the molecular mechanisms at play when hypertension and diabetes cause kidney damage.

“This project was a great way to foster a new interdisciplinary collaboration, because we’re biomedical engineers, and she’s a kidney physiologist,” Parigoris said.

Zhao added, “I was grateful that the Takayama lab reached out — this is a great opportunity for my lab. We’re interested in what we can learn from studying This proximal tubule kidney organoids, which let us observe organoid is 30 days old, and natural functions very closely. I see this will survive at least another 60 as a powerful new tool for further invesdays. The 90-days is a record tigations, not only in kidney disease, but for a drop culture of any kind.

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OUR RESEARCH

Looking Deep Within Stem Cells Organelles — the bits and pieces of RNA and protein within a cell — play important roles in human health and disease, such as maintaining homeostasis, regulating growth and aging, and generating energy.

Organelle diversity in cells not only exists between cell types but also within individual cells. Studying these differences helps researchers better understand cell function, leading to improved therapeutics to treat various diseases.

Two studies from the lab of Ahmet F. Coskun, a Bernie Marcus Early Career professor in Coulter BME, examined a specific type of stem cell with an intracellular toolkit to determine which cells are most likely to create effective cell therapies.

“We are studying the placement of organelles within cells and how they communicate to help better treat disease,” said Coskun. “Our recent work proposes the use of an intracellular toolkit to map organelle bio-geography in stem cells that could lead to more precise therapies.”

The first study, published in Scientific Reports, a Nature portfolio journal — looked at mesenchymal stem cells (MSCs) that have historically offered promising treatments for repairing defective cells or modulating the immune response in patients. In a series of experiments, the researchers created a data-driven, single-cell approach through rapid subcellular proteomic imaging that enabled personalized stem cell therapeutics.

The researchers then implemented a rapid multiplexed immunofluorescence technique in which they used antibodies designed to target specific organelles.

By fluorescing antibodies, they tracked wavelengths and signals to compile images of many different cells, creating maps. These maps then enabled researchers to see the spatial organization of organelle contacts and geographical spread in similar cells to determine which cell types would best treat various diseases.

“Usually, the stem cells are used to repair defective cells or treat immune diseases, but our micro-study of these specific cells showed just how different they can be from one another,” said Coskun. “This proved that patient treatment population and customized isolation of the stem cells identities and their bioenergetic organelle function should be considered when selecting the tissue source. In other words, in treating a specific disease, it might be better to harvest the same type of cell from different locations depending on the patient’s needs.”

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Wallace H. Coulter Department of Biomedical Engineering

In the second study, published in Cell Reports Methods, the researchers took the toolkit a step further, studying the spatial organization of multiple neighboring RNA molecules in single cells, which are important to cellular function. They evolved the tool by combining machine learning and spatial transcriptomics. They found that analyzing the variations of gene proximity for classification of cell types was more accurate that analyzing gene expression only.

“The physical interactions between molecules create life; therefore, the physical locations and proximity of these molecules play Coskun important roles,” said Coskun. “We created an intracellular toolkit of subcellular gene neighborhood networks in each cell's different geographical parts to take a closer look at this.”

The experiment consisted of two parts: the development of computational methods and experiments at the lab bench. The researchers examined published datasets and an algorithm to group RNA molecules based on their physical location. This “nearest neighbor” algorithm helped determine gene groupings. On the bench, researchers then labeled RNA molecules with fluorescents to easily locate them in single cells. They then uncovered many features from the distribution of RNA molecules, such as how genes are likely to be in similar subcellular locations.

Cell therapy requires many cells with highly similar phenotypes, and if there are subtypes of unknown cells in therapeutic cells, researchers cannot predict the behavior of these cells once injected into patients. With these tools, more cells of the same type can be identified, and distinct stem cell subsets with uncommon gene programs can be isolated.

“We are expanding the toolkit for the subcellular spatial organization of molecules — a ‘Swiss Army Knife’ for the subcellular spatial omics field, if you will,” said Coskun. “The goal is to measure, quantify, and model multiple independent but also interrelated molecular events in each cell with multiple functionalities. The end purpose is to define a cell’s function that can achieve high energy, Lego-like modular gene neighborhood networks and diverse cellular decisions.” ‣ GEORGIA PARMELEE

Tech-Emory Collaboration on Cancer Disparity Gets NIH Boost Diffuse large B-cell lymphoma (DLBCL) is a fast-growing, aggressive, and all-too-common form of non-Hodgkin lymphoma. And even though white people in the U.S. are more likely to develop it, people of African descent are diagnosed 10 years earlier, on average, and their 5-year survival outcome is much worse.

Researchers Ankur Singh and Jean Koff want to find out why and the National Cancer Institute is supporting their efforts with a $2.76 million, five-year R01 grant.

Using advanced sequencing and spatial-omics analysis, together with novel patient-derived organoids developed in Singh’s lab, the researchers plan to study the interactions between patient-level factors, tumor genetics, and the tumor microenvironment as features that contribute to racial disparities in diagnosis, survival, and treatment.

“Once we identify factors that differ in African American patients, my lab will immune engineer lymph node-mimicking technologies to study these tumors and discover new therapies,” said Singh, associate professor in the Coulter Department and the George W. Woodruff School of Mechanical Engineering at Georgia Tech. “The project is a true collaboration between a bioengineer and an oncologist.”

Koff, a clinical expert in B-cell lymphoma, leads the non-interventional research team in lymphoma at Emory's Winship Cancer Institute, where she focuses on defining the immunologic and genetic factors impacting survival and response to treatment in lymphoma patients. Her team has established a specialized research tissue collection system at Winship.

“Our findings that African American patients are diagnosed at a younger age and exhibit specific tumor

genetic abnormalities strongly suggest a biologic component to this disparity, but how race-specific differences in tumor immune microenvironment affect lymphoma outcomes has not been well defined,” said Koff.

Singh’s pioneering work developing and deploying modifiable organoids and on-chip systems to model benign and malignant lymphoid tissue, she added, “is an outstanding resource for investigating unanswered questions about how tumor microenvironmental factors influence response or resistance to certain therapies.”

Singh and Koff, co-principal investigators on the project, are joined by Coulter Department Assistant Professor Ahmet Coskun, who specializes in multiplex imaging.

“Collectively, our team will investigate the difference between African American patients versus other ancestries, leading to innovative technologies that will answer questions related to racial disparities in this type of cancer,” said Singh.

Ultimately, they want to apply what they learn to the development of targeted treatments aimed at reducing disparities and improving outcomes for patients. It’s the big target in a collaboration that began before Singh arrived in Atlanta.

“Ankur and I have really enjoyed working together since we first learned he was relocating from Cornell to Georgia Tech,” Koff noted. “We quickly realized that our research interests and areas of expertise complement each other very well. I think our ongoing close collaboration truly exemplifies a winning Emory-Georgia Tech partnership.” ‣ JERRY GRILLO

Ankur Singh (top) and Jean Koff.

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OUR RESEARCH

Exploring the Mechanisms Behind Flicker Annabelle Singer was a postdoctoral researcher at the Massachusetts Institute of Technology when she helped develop a light and sound therapeutic system that opened the door to a hopeful future of non-invasive treatments for neurodegenerative diseases.

Singer, now a biomedical engineer at Georgia Tech, has since demonstrated dramatic success in treating mouse models of Alzheimer’s disease with flickering lights and buzzing sounds. Two years ago she and her team completed the first human feasibility study of this “flicker” treatment, delivered to patients via goggles and headphones.

“And there’s a long list of clinical trials going on right now using flicker stimulation — people are using the technology in a variety of different contexts,” said Singer, an assistant professor in Coulter BME. “But the mechanism underlying all of this is a major mystery. As scientists, we want to nail down the one key question: What is actually happening?”

She’s been piecing the flicker mystery together for years, along the way building a novel way to manipulate the neuroimmune system and prevent Alzheimer’s damage.

Her prior work focused on using flickering light and sound set to a frequency of 40 Hertz (40 times per second) to stimulate gamma waves, which play a main role in functions such as perception and memory, and which are deficient in Alzheimer’s disease. Singer’s flicker treatment set neurons on a rhythmic dance that recruit microglia, the brain’s primary immune cells, which engulf pathogens and secrete cytokines — small proteins that alert other immune cells to the cause.

Now Singer and a team of multidisciplinary researchers from Georgia Tech and Emory have provided answers to that one key question.

W. Woodruff School of Mechanical Engineering at Georgia Tech, and Dieter Jaeger (professor in Emory’s Department of Biology). Both also have appointments in the Coulter Department. The lead authors are Ashley Prichard, postdoctoral researcher in Singer’s lab and Kristie Garza, former graduate researcher in the lab.

And for this research, they took a slightly different, healthier approach from past studies.

“In the past, our focus was on the diseased state. It was important for this research that we focus on brain rhythms in the healthy brain, to see the effects of sensory stimulation outside the context of Alzheimer’s pathology,” Singer said.

Also, this time the team used flicker

STUDYING RHYTHM IN A HEALTHY BRAIN Singer’s collaborators include fellow faculty researchers Levi Wood, associate professor in the George

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Wallace H. Coulter Department of Biomedical Engineering

stimulation to induce electrical activity at two different frequencies in mice: 40Hz, corresponding to gamma brain waves; and 20Hz, corresponding to beta waves. “We compared different frequencies, so we’d have a better idea of the effects on the rhythmic activity of neurons,” said Singer.

“That’s important because different frequencies of activity have distinct effects on microglia and cytokines.”

Previously, the team noted the effects of different frequencies on cytokine protein expression — for example, 20Hz flicker could induce neural activity, but led to lower cytokine expression, which can be a good thing. Cytokines are necessary for a healthy immune system, but in the right amounts – cytokines run

OUR RESEARCH

Faculty researchers Annabelle Singer, left, and Levi Wood are probing the mechanisms underlying the flicker technology. (PHOTOS: ALLISON CARTER)

amok can lead to harmful inflammation.

Also, it turns out that these important little proteins are not limited to immune cells like microglia. According to Wood, “We thought the cytokines might come from other kinds of cells, too. So, we isolated the nuclei from different cells in the brain and looked at the genes affected by forty Hertz flicker.”

And they found that 40Hz will stimulate immune genes in those neurons. “We also found changed genes in microglia, but they were mainly involved in controlling cell shape or morphology,” Wood said.

Indeed, the team saw the effects that different frequencies can have on the microglia, dramatically altering its morphology — its shape and function.

“Forty Hertz and twenty Hertz were both different from no stimulation at all, and in opposite directions,” Singer said.

At 20Hz, microglia assumed their ramified, surveillance mode — lots of branches, or dendrites, reaching out from the cell body. At 40Hz, they look more like amoeba, an amorphous blob that eats, or DIFFERENT SHAPES, DIFFERENT FUNCTIONS engulfs, pathogens.

At 20Hz, microglia assumed their ramified, surveillance mode — lots of So, microglia do a branches, or dendrites, reaching out from different dance based the cell body. At 40Hz, they look more like amoeba, an amorphous blob that eats, on the rhythm. or engulfs, pathogens. So, microglia do a different dance based on the rhythm.

Furthermore, their research revealed an underlying mechanism allowing all of this to happen. It’s a protein complex called nuclear factor kappa

B, or NFkB. This signaling mechanism, which regulates immune function, is the pathway that links flicker stimulation to inspire the brain rhythms and the resulting immune response.

Singer, who is a mother, compared these different effects to a toddler making his way in the world. “When microglia surveil their environment, they stretch out to the things around them, like a toddler touching ever dirty thing they can get their hands on,” she said. “And when microglia enter their engulfing state, it’s like a toddler sticking everything in their mouth.”

She added, “The important thing is, in some disease contexts, you want the surveillance state — you want to turn down the immune response. In others, you want the more active, engulfing state that we see at the higher frequency.”

So, a different kind of stimulation for a different disease state? Or a new, non-invasive way to maintain an already healthy brain? Possibly both, eventually.

“The potential is, we can non-invasively manipulate the brain’s immune system in either direction, turning it up or turning it down, depending on the stimulation,” Singer said. “That has important implications for using this technology in a lot of different ways, in the presence of disease, or as way to boost this function or that function.” ‣ JERRY GRILLO

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OUR RESEARCH

Serpooshan Lab Creates New 3D-Printed Tool to Study Deadly Childhood Cancer Neuroblastoma is a terrifying word for parents of young kids. This solid tumor cancer develops in the nerve tissue, primarily affects infants, and typically comes with a grim prognosis.

“There is a very high morbidity and mortality rate for these babies,” said researcher Vahid Serpooshan, an assistant professor in Coulter BME, whose lab develops tissue engineering technologies to study pediatric cancers.

Despite advances in treatment, neuroblastoma still accounts for about 15% of all pediatric oncology deaths.

And more than half of those patients who do respond eventually relapse.

“Even with advanced treatments that have been successful, like chemoimmunotherapies, some of these babies will respond, and some won’t respond at all,” Serpooshan said. “We don’t really know exactly what is going on, and that is a huge dilemma. Part of the problem is pediatric cancer in general has not been intensively studied as a specific and distinct disease. We need to develop better research tools.”

With that in mind, Serpooshan’s lab has collaborated with Emory pediatric oncologist Kelly Goldsmith to create a new 3D printed, dynamic model of pediatric neuroblastoma tumors that could lead to improved, personalized treatments for young patients.

Serpooshan and his team focus on the neuroblastoma tumor microenvironment and its influence on tumor behavior and the tumor's response to therapy. These interactions are critical in cancer progression, metastasis, and response to therapies.

“In recent years, this has become an area of great research interest, but there is a lack of reliable and biomimetic experimental models,” said Serpooshan, whose team developed an in vitro model of neuroblastoma using a relatively new technology called 3D bioprinting.

Instead of utilizing metals and plastics to create a device or model, as in traditional 3D printing, the bioprinting technique uses materials like cells and hydrogels to create functional 3D tissues.

These materials, called bioink, mimic the composition of human tissues.

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An artist's rendering of Serpooshan's model.

Serpooshan’s lab has been a pioneer in using bioprinting in tissue engineering and regenerative medicine applications, which is the group’s primary focus. For this project, the researchers applied a hydrogel called gelMA as the bioink.

Then human-derived neuroblastoma spheroids (3D cell cultures that mimic tissues and microtumors) and human vascular endothelial cells (the cells lining blood vessels) were incorporated into the bioprinted gelMA to create a working model of the neuroblastoma tumor microenvironment.

The researchers manufactured their model and studied the processes of cancer under static and dynamic conditions — static, when nothing is really moving through the system, is the approach most often used in drug screening with in vitro applications, “which is a big limitation,” Serpooshan said.

To track the tumor under more realistic, or dynamic, conditions, researchers used a bioreactor to simulate blood flow through the vasculature.

Their analysis of the tumor environment under these conditions offered the most

Wallace H. Coulter Department of Biomedical Engineering

effective representation of what goes on between tumor cells and the vasculature, demonstrating in three dimensions how aggressively a tumor can grow, and how it may or may not respond to drugs.

“This is just a first step, but we’re very excited for having developed such a robust platform that can be adapted for a lot of future research applications,” Serpooshan said.

They’re starting with neuroblastoma, because Goldsmith’s lab has access to neuroblastoma cells from a variety of different patients and sources that now can be studied in a new way.

“Some of these patients already have shown resistance to chemoimmunotherapy,” Serpooshan said. “So we can take advantage of this clinical data and create different models, drill down to the basic cellular and molecular mechanisms at play, and potentially come up with scenarios and strategies to help those patients who are resisting the drugs. Now we can move forward and ask more meaningful and clinically relevant questions.” ‣ JERRY GRILLO

OUR RESEARCH

Karmella Haynes Leads Exploration of the Genome’s Dark Regions Karmella Haynes wants to shine some light on the “dark matter” of the genome, and the National Science Foundation (NSF) is helping her flip the switch.

Haynes, assistant professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, is leading a team of multi-disciplinary investigators who were awarded a four-year, $2.1 million grant from NSF to explore this dark matter and illuminate how the genome controls living systems in all their diversity and complexity.

It’s large space to explore. Only two percent of the human genome is known to be responsible for engineering proteins, a process essential to higher functioning life. This leaves 98 percent of the genome as a biological frontier known as dark matter — these segments do not encode for protein, like the other two percent.

“A lot of progress has been made in studying this part of the genome, but what we don’t know yet can be very useful,” said Haynes, whose lab works on the front line of synthetic biology, and is typically dedicated to protein engineering, including the investigation and design of chromatin-based systems for controlling gene expression in cancer and other cells.

For this project, funded through February 2027, Haynes is shifting her focus from protein engineering to RNA engineering, noting that some of those dark regions of the genome can produce long noncoding RNAs (lncRNAs). Usually found in very small amounts within a cell, lncRNAs have nonetheless been found to have an impact on biological processes like cell growth and survival, cell identity and environmental interactions, and various human and animal diseases.

“The next step would be to tap into the biomedical and biotechnology potential of these RNAs,” said Haynes, who is principal investigator on the multi-institutional project. Her co-principal investigators are Alisha Jones, assistant professor of chemistry at New York University, and Keriayn Smith, assistant professor of genetics at the University of North Carolina-Chapel Hill. Joining them are Emory biochemist Anita Corbett; Tian Hong, a computational

biologist at the University of Tennessee; and Aaron Johnson, a molecular geneticist at the University of Colorado.

Together, they’ll delve into the mysteries and mechanisms of lncRNA. INVESTIGATORS, ASSEMBLE! Haynes met her collaborators at an NSF Ideas Lab gathering in the summer of 2022. The program had an acronym that sounds like something borrowed from Star Wars, D2R2, which actually stands for Dark Dimensions of the RNA Regulome. Ideas Labs are intensive workshops facilitated by NSF with the intention of finding innovative solutions to grand challenges.

D2R2 brought together engineers, chemists, mathematicians, computer scientists, and others with a goal of developing new theories and models for understanding non-coding RNAs, and new approaches for manipulating and controlling non-coding RNA activity.

“We all received a crash course on what the scientific community understands about all of this, then we got work,” said Haynes.

Her two co-PIs, Jones and Smith, help comprise what Haynes believes is a unique leadership trifecta. “I rarely hear of a large multi-institutional grant that is led by three black women. I think that is significant.”

Also significant, she added, is the project’s emphasis on outreach. Haynes and her team have reached out to the students of Project ENGAGES

at Georgia Tech – a high school science education program in partnership with minority-serving public schools in Atlanta. The plan is to provide the students a focus presentation on RNA technology.

Ultimately, Haynes hopes the NSF project will yield innovations that would enhance our ability to predict and mitigate the effects of changing environments on organisms and ecosystems – in other words, epigenetic control. If they can engineer lncRNAs to fine tune their activity, researchers should be able to generate beneficial biomolecules for biomedical applications.

“We expect to really push the boundaries of what we know,” Haynes said. “But if we could develop a tool for this kind of epigenetic silencing, that would be cool.

This could have some exciting implications for bioengineering.” ‣ JERRY GRILLO

(PHOTO: JERRY GRILLO)

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Wallace H. Coulter Department of Biomedical Engineering

BME RESEARCHERS DIG DEEP INTO

Computational Neuroscience THE HUMAN BRAIN, WITH ITS 86 BILLION NOISY NEURONS, IS A RELIABLE, DURABLE, COMPLEX, AND CRYPTIC BIOLOGICAL SUPERCOMPUTER. A growing cadre of multidisciplinary researchers at Georgia Tech and Emory University is trying to leverage that neuronal chatter, and what they discover may hold the key to better treatments for disease and addiction, advanced robotics, and more useful, human-centered artificial intelligence (AI).

These researchers all are using computational neuroscience — a branch of neuroscience that employs mathematical models, computer simulations, and theoretical analysis of the brain to gain a deeper understanding of the nervous system.

"We want to understand the brain and the important data that we gather from this amazing, mysterious organ,” said Chethan Pandarinath, assistant professor of biomedical engineering. “For a long time, we really didn’t have the adequate tools. But there has been an explosion of technology over the past five or 10 years. So, we’re moving into a different space in the ways we approach the brain, and the ways we think about it.” Computational neuroscience has expanded steadily at Georgia Tech and Emory since President Barack Obama’s BRAIN Initiative identified it as a research priority. BME researchers have been answering the call, working with biologists, psychologists, mathematicians, physicists, and data scientists to make Atlanta a global center for computation and brain research.

The research wish-list still includes improvements in machine learning, AI, and crowdsourcing approaches to translate the massive volume of data being gathered from human brains. Here is a small sampling of the researchers working within Coulter BME who are connecting the brain’s neuronal dots and expanding this body of work.

by JERRY GRILLO

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COMPUTATIONAL NEUROSCIENCE

HANNAH CHOI Assistant Professor, School of Mathematics; Coulter BME program faculty Principal Investigator of Research Group in Mathematical Neuroscience Neuroscience wasn’t part of her plans, but while working toward her Ph.D. in applied mathematics, “I got really interested in nonlinear dynamical systems, a big topic in applied mathematics,” said Choi, whose primary faculty appointment is in the School of Mathematics but has an appointment in Coulter BME, too.

Dynamical systems are chaotic, unpredictable, and counterintuitive — pretty much like most systems in nature. “I soon realized the brain is the most exciting nonlinear dynamical system, and that I could apply my mathematical tools and develop computational theories to better understand the brain,” Choi said.

Choi’s work in applying math to neuroscience earned her a prestigious 2022 Sloan Research Fellowship, which goes to the nation’s most promising young scientific researchers. Since launching her lab at Georgia Tech in January 2021, Choi has continued her collaboration with the Seattle-based Allen Institute in studying how information is processed in neural networks of many different scales, while starting partnerships with several Georgia Tech and Emory researchers, including Simon Sponberg, Anqi Wu, Nabil Imam, Chris Rodgers, Ming-fai Fong, and Dieter Jaeger.

Like some of her Georgia Tech colleagues, Choi also wants to address the problem of the environmental footprint being made by all of this computation and AI. “The idea is to apply what we have learned about our very energy-efficient brains to the development of better, more efficient artificial neural networks.”

EVA DYER Assistant Professor, Coulter BME Principal Investigator of the Neural Data Science (NERDS) Lab Dyer leads a diverse team of researchers in developing machine learning approaches to analyze and interpret massive, complex neural data sets. Winner of a McKnight Technology Award and BRAIN Award in recent years, Dyer’s interest in the brain is rooted in her love of music — she’s always been interested in how humans perceive sound at the neuronal level.

As a postdoctoral student she developed a cryptography-inspired strategy for decoding neural conversations. Now one of the leading young researchers in computational, Dyer directs a lab that routinely presents research at high-profile conferences like NeurIPS. Her team is “essentially interested in how the coordinated activity of large collections of neurons are being modified or changing in the presence of something like disease,” she said.

“Ultimately, with the information we gather and analyze, we hope to discover biomarkers of Alzheimer’s and other diseases,” added Dyer. “The idea is to catch changes in neural activity that are happening before we actually see the cognitive deficits.”

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Wallace H. Coulter Department of Biomedical Engineering

COMPUTATIONAL NEUROSCIENCE

BILAL HAIDER Associate Professor, Coulter BME Principal Investigator of Haider Lab

Ultimately, with the information we gather and analyze, we hope to discover biomarkers of Alzheimer’s and other diseases. The idea is to catch changes in neural activity that are happening before we actually see the cognitive deficits.”

Haider is interested in how the brain creates visual perception, and how factors like alertness and attention improve visual functions. His team makes use of cutting-edge optical and electrical technologies and computational tools to record, manipulate, and interpret the electrical messages passed between neurons of multiple visual brain areas in mice.

“These are exciting times to be at the intersection of systems and computational neuroscience,” said Haider, whose lab has been supported by the Sloan Foundation, the BRAIN Initiative, and the NIH’s National Institute of Neurological Disorders and Stroke. His Coulter Department collaborators include Garrett Stanley and Hannah Choi, “who provides great computational insights,” he said.

Haider’s research seeks to unravel how visual functions fail in neurological conditions where perception and behavioral actions are impacted, such as autism – work that has been funded by multiple awards from the Simons Foundation Autism Research Initiative (SFARI).

“We are collecting data we could only dream of a few years ago, and it is exciting to make sense of it with our diverse team of students, new computational tools, and collaborators with different expertise,” he said. “And we are all motivated by one of the biggest challenges in biomedical engineering – unraveling how the brain actually works, so that we can learn how to fix it.”

Eva Dyer

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CHETHAN PANDARINATH Assistant Professor, Coulter BME Principal Investigator of Systems Neural Engineering Lab Pandarinath’s lab uses AI tools and the insights gained from the brain’s neural networks, with support from the National Institutes of Health, to develop revolutionary assistive devices for people with disabilities or neurological disorders.

Endeavoring to expand the field of research, he spearheaded the Neural Benchmarks Challenge, which debuted in 2022. The competition attracts a diverse range of teams that created new models for analyzing large data sets of neural activity.

“This was our effort to accelerate progress at the intersection of neuroscience, machine learning, and artificial intelligence,” said Pandarinath, who is part of the leadership team for the Emory Neuromodulation Technology Innovation Center (ENTICe), a partnership between Georgia Tech and Emory.

The benchmarks challenge, he said, illustrated a need for multiple perspectives and disciplines in computational neuroscience — the winning team of the first competition was a firm called AE Studio, a software development, data science, and product design company that doesn’t ordinarily focus on neuroscience but develops potent mathematical and machine-learning tools.

“The results of the competition reflect the multidisciplinary and collaborative nature of this field of research,” Pandarinath said.

CHRIS ROZELL Julian T. Hightower Chair, School of Electrical and Computer Engineering; Coulter BME program faculty Principal Investigator of Sensory Information Processing Lab Rozell describes his lab’s focus as, “a combination of data science, neurotechnology, and computational modeling,” with the goal of advancing the understanding of brain function, leading to the development of intelligent machine systems and effective interventions for disease.

“One of the projects in our lab that is really compelling right now is a novel therapy for patients with treatment-resistant depression,” said Rozell, a member of the ENTICe executive council. His lab is partnering with a clinical team to improve this experimental treatment for patients who have not responded to any currently approved therapy. “So, no drugs help them. No psychotherapy. No electroconvulsive therapy. We’re using deep brain stimulation.”

The results have been positive for patients, and the researchers are, “getting an objective readout, for the first time, of what’s happening in their brains,” Rozell said, thanks to a new generation of machine-learning tools called ‘explainable AI.’ “With these new approaches, we can gain a deeper understanding of the disease, which can lead to more personalized therapies,” said Rozell, part of the leadership team of the Georgia Tech/Emory Computational and Neural Engineering Training Program, an educational and research training program funded by the NIH.

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Wallace H. Coulter Department of Biomedical Engineering

COMPUTATIONAL NEUROSCIENCE

GARRETT STANLEY McCamish Distinguished Chaired Professor, Coulter BME Co-director of Neural Engineering Center Principal investigator of the Lab for the Control of Neural Systems Stanley’s lab focuses on information processing in the brain, combining experimental neuroscience and neuro-engineering (for example, multi-electrode recording) with computational approaches (think of machine learning and control theory).

Collaborating with biologists, psychologists, computer scientists, and mathematicians, the Stanley lab develops and uses approaches in engineering control theory and machine learning to read and write signals in brain circuits (signals that enable us to sense the world through touch, learn about our environments, make decisions, and take action).

“The brain is like a massive computer, so bringing computational tools in to study the brain and studying the brain’s own computational strategies are like speaking its language,” said Stanley, who is also part of the leadership team of the Computational and Neural Engineering Training Program. “That’s really critical for understanding the brain and developing treatments for neurological disorders and diseases.”

His team’s latest work involves taking computational models and ideas, “and implementing them into hardware, making them work in real-time for interacting with the brain,” said Stanley. “The centerpiece of this work is an optimal control strategy for controlling brain circuits, something we borrowed from the same ideas used to control airplanes and cars.”

LENA TING Lena Ting, right, applies motion capture sensors to postdoctoral fellow Surabhi Simha for a standing balance test with robotic ankle exoskeleton boots. (PHOTO: CANDLER HOBBS)

McCamish Distinguished Chair Professor, Coulter BME Co-director of Neural Engineering Center Director of the Neuromechanics Lab Lena Ting is interested in the relationship between the nervous system and the musculoskeletal system – the connection between how our balance and our cognition, and how they impact each other. Her creative, in-depth exploration of this complex and flexible interplay has included dancers, flamingoes, and exoskeletons. And lots of computation.

“It’s essential to have a computational understanding of the workings of the body, whether it’s the brain, the nervous system, or the muscles, so computation has always played a central role in my work,” said Ting.

Her lab also depends on a wide range of disciplines and techniques, including neuroscience, biomechanics, rehabilitation, robotics, and physiology, to closely study human mobility, with the overarching goal of advancing our knowledge of movement disorders and the mechanisms of rehabilitation.

“But it’s amazing how much we can do with computer modeling – we can move a long way down the field, as they say, before we get the point of attaching something to something else with a pulse,” said Ting, who serves with Stanley and Rozell on the executive committee of the Georgia Tech/Emory Computational and Neural Engineering Training Program, which is preparing a new generation of researchers focused on deciphering puzzles of the brain and nervous system.

“It’s sort of the heart of our computational neural engineering community,” Ting said.

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Coulter BME

ON TOP

F

or Prof. Michael Davis, associate chair for graduate studies, a no. 1 ranking for the Wallace

H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University comes as no surprise.

Placing a priority on research and a push to expand integrative core courses and advanced seminars that merge studies in medicine and engineering, graduate biomedical students are beginning their programs with a cross-discipline approach that prepares them for a growing and competitive biotech industry.

“I think it's a long time coming based on all the changes we've made and our commitment to graduate education,” he said, “It's not just about being the biggest program—we provide our students unique opportunities in terms of flexible curriculum geared toward their research focus areas.”

b y K E L LY P E T T Y

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Wallace H. Coulter Department of Biomedical Engineering

PHOTO: Joshua Stewart

While the undergraduate program has routinely been placed among the best in the country, the top national ranking is the first for the graduate program in the department’s history. U.S. News and World Report reviewed several factors including research activity, number of doctoral degrees awarded, and student acceptance rate.

Graduate programs in the Coulter Department are comprised of various pathways and research specialties tailored to a students’ academic goals.

Three master’s degrees encompass biomedical engineering, innovation and development, and robotics. Those interested in doctoral studies can enroll in the joint biomedical engineering Ph.D. programs between Emory University and Georgia Tech, or through a partnership trio between Emory, Georgia Tech, and Peking University in China for a global health perspective.

The department also engages in several interdisciplinary doctorate programs that give students an opportunity to specialize in areas such as bioengineering, bioinformatics, computational science, machine learning and robotics.

“What we want is our students to tackle medical problems using

quantitative and engineering solutions,” Davis said. “We want students that come to our program who are diverse and have life experience. Whether you're from Texas or South America, we want you here to contribute to the next generation of solutions to medical problems.”

FROM LABS TO THE BEDSIDE, GRADUATE STUDENTS FIND OPPORTUNITY AT EVERY CORNER Since the first Ph.D. students enrolled in 2000, the Coulter Department has forged an intentional path to train future leaders in biomedical engineering, advancing research and scholarship in the field both nationally and abroad.

“We're not just a biomedical program or engineering program,” Davis explained. “[We’re] biomedical engineering—students need to learn to speak both languages.”

Master’s programs are designed for various career pathways and students have a choice between non-thesis or thesis options to either build their credentials or seek out laboratory opportunities to gain the research experience needed to move into a Ph.D. program.

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For those interested in the business and commercialization side of the biomedical industry, the Coulter Department offers a master’s in biomedical innovation and design (MBID). Davis said program participants take classes wholly different from other master’s students.

“So, a regular master student could take anything from our graduate curriculum, but the MBID program is a very set curriculum that involves product development, prototyping, and marketing.

And it's taught by people who can put a business spin on [the curriculum],” Davis said.

At Emory University’s School of Medicine, the Coulter Department offers a second MBID program that focuses on advanced therapeutics for those desiring to explore the clinical side.

Students are immersed in a multi-disciplinary curriculum centered around cell therapy, gene therapy, tissue engineering, and regenerative medicine.

“There are fundamentals, but we want our students to learn about how you might design a drug based on a target model, how you move it through testing then to licensing,” Davis said. “So once again, it's not just a traditional masters, it's something that's directly focused to get students ready for what's to come in the real world.”

The other specialized master’s program in robotics is a collaborative effort between the Coulter Department and five other disciplines at Georgia Tech—mechanical engineering, electrical & computer engineering, aerospace engineering, interactive computing, and physics—offering students wide-ranging coursework to train them for careers in the design and development of robotics and automated solutions.

“We have specialties in everything. If you want to do it, you can find it here,” Davis said. “We want students who are willing to take risks and willing to push the envelope in order to succeed.”

From the start, students in the Coulter Department’s graduate programs are supported by faculty who are leaders in their specialties and can mentor students throughout their academic career. Add to that, the Coulter Department has forged dynamic relationships with the Centers for Disease Control and Prevention, Children’s Healthcare of Atlanta, and Emory Healthcare.

“We’re unique here in Atlanta where we have a top engineering school, top medical school and a top children's hospital all within a few miles of each other,” Davis said. “In fact, that's one thing we're trying to institute at the graduate level is clinical immersion—we want students to get out and be able to talk the talk of clinicians.”

He added, “They’ll be going to drug and medical device companies, and they’ll have to interact with patients and doctors. If you can't speak the language of the doctors, how can you solve the problems they're trying to fix?”

Davis said the department’s rich alumni network has also yielded Wallace H. Coulter Department of Biomedical Engineering

“It's this sort of great network where we send our students out to the best companies and they understand the value of what our students can bring,” Davis said.

Employing a strategy of building a diverse talent pool for the biomedical engineering field – whether that is in industry or academia – has paid off for graduate students in recent years.

Mohammad Sendi, ’22, won a grant in 2021 from Bio-Medical Instruments and the Foundation for Neurofeedback and Neuromodulation Research while earning his doctorate from the Coulter Department. He used the grant to better study the effects of brain stimulation for PTSD patients using EEG scans.

He currently works as a postdoctoral research fellow at Harvard Medical School.

In the same year, Joshua Lewis ‘20, worked in the lab of Melissa Kemp, Ph.D., the Carol Ann and David D. Flanagan Professor, to

“We want students who are willing to take risks and willing to push the envelope in order to succeed.”

Critical to the success of students in the Ph.D. program is collaboration and innovation, Davis said. With nine research areas ranging from neuroengineering to cancer technology, students are not limited in what they can pursue.

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numerous internship and professional development opportunities placing students in front of major employers in the biotech space both in Atlanta and around the country.

Michael Davis

further his research on treating brain disorders through neuromodulation. Through a partnership with Wake Forest University and Kemp’s support, Lewis was able to publish the study in Nature Communications.

Cydney Wong, a Ph.D. candidate, and current graduate assistant in the Coulter BME department, was named one of 21 Science ATL Communications Fellows in 2021, broadening her knowledge of science communication to bring greater public awareness to glaucoma research.

Eight students earned fellowships from the National Science Foundation in 2022 to conduct cell research for cancer immunotherapy, immune-related diseases, and stem cell therapies.

And In the spring of 2023, 6th year graduate student Nettie Brown was one of six individuals to receive the GT NEXT award from the Georgia Tech Office of Technology Licensing. Mentored

by Prof. Johnna Temenoff, Brown will use the $5K award to boost her dissertation research around the utilization of biocompatible materials and the delivery of cartilage materials to promote facial cartilage regeneration, especially for ear and nose reconstruction applications.

Other graduate alumni have gone on to join venture capitalist firms for biotech startups and returned to the Coulter Department to serve as full-time faculty.

“I would say our student is brave,” Davis said. “We want students who are willing to take risks and push the envelope in order to succeed, and I think we get that for the most part.”

A PROMISING FUTURE FOR GRADUATE EDUCATION IN COULTER BME Over the last decade, the Coulter Department has made significant strides in building a robust graduate program centered on research, innovation, and technology.

In 2009, a partnership between Georgia Tech, Emory, and Peking University launched the global health focused biomedical engineering Ph.D. program. A few years later in 2013, the master of biomedical innovation and development (MBID) program was formed to move the department further into the commercialization space.

The department recently launched its combined bachelors/masters biomedical engineering program, offering undergraduate students an opportunity to advance their studies and earn two degrees in about five years.

And predoctoral students in biomedical engineering and bioengineering now have an opportunity to train for careers in the cardiovascular field. The Coulter Department opened registration in Spring 2023 for its Cardiovascular Biomechanics Graduate Training Program at Emory University and Georgia Tech, where students will do lab rotations to study a range of disciplines including cardiovascular biomechanics, medical imaging, therapeutics discovery and delivery, and data science.

from Virginia Tech. Her passion for broadening opportunities for students who are of color or LGBTQ+ is pushing the Coulter Department to the forefront of engineering education.

“The emphasis on engineering education definitely makes our program stand out from the crowd, based on implementing research-based practices to shape our educational mission and novel assessment practices that include the importance of equity in all our BME research including, how we educate future bioengineer,” Cross said.

Rachel Pitts Hall, Director of Faculty and Student Training, is transforming the career advancement side of the department’s graduate programs, integrating professional development into courses for second-year students based on feedback heard from current students, alumni, and faculty.

“I think we will be further incorporating the work we've done at the undergraduate level into our graduate courses and how we teach them. I also think there will be more integration and crossover between our three graduate programs, Ph.D., M.S., and MBID, to benefit all students who graduate from our department,” Hall said. “I hope we continue to push for an environment where our students will be supported, met where they are, and mentored to help them be the best version of whatever they want to be.”

“I think we don't want to rest on our laurels,” Davis said. “We never have been one to do so, but we've constantly tried to innovate.”

Davis believes the future is bright for graduate biomedical engineering education in the Coulter Department. To reach a greater number of prospective students, he said the next step is to continue to view students wholistically. Going beyond GPA and test scores and assessing a student on their accomplishments, goals, and their life story will be critical to finding those individuals that fit the profile of a Coulter biomedical engineering student.

Expanding graduate program offerings and innovative curriculum tracks can only be made possible by bringing on the right faculty, Davis said. Faculty recruiting for the graduate level has shifted recently to finding individuals who have non-traditional

“We don’t want a student who leaves who can just critically solve problems, or a student who can memorize an equation,” Davis said. “You can take out your phone and Google that, but you can't Google problem solving, or empathy, or innovation. So how do

Earning the top ranking in the nation for graduate education doesn’t mean the work stops.

Joshua Lewis ‘20, worked in the lab of Melissa Kemp, Ph.D., the Carol Ann and David D. Flanagan Professor, to further his research on treating brain disorders through neuromodulation. Lewis and Kemp published their study in Nature Communications.

(PHOTO: Joshua Stewart).

engineering backgrounds.

Take Assistant Professor Kelly Cross for example. Cross came to Georgia Tech with a bachelor’s from Purdue University in chemical engineering and a doctorate in engineering education

we take concepts which our students need, like creativity, and bring it into the curriculum? And so, I think we’re going to be more focused on the whole student.”

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OUR COMMUNITY

Our Community Ahmet Coskun Wins 2023 BMES-CMBE Rising Star Award Georgia Tech faculty member Ahmet Coskun has been named a Rising Star by the Biomedical Engineering Society (BMES) Cellular and Molecular Bioengineering (CMBE) Special Interest Group.

He is the first faculty member from Tech to receive the award in more than a decade.

The award recognizes a handful of outstanding junior investigators every year for work that advances the medical field through the study of cells, molecules, and microenvironments. BMES honored Coskun for his work on microscale metabolic imaging for cancer treatment. His team explores the connections between metabolism and immunity and examines cancer patients’ responses to treatments based on their individual lifestyles.

Coskun said examining cells on a micro-scale is the future of medicine, and he hopes the award will help him make immunotherapy more efficient.

“There’s no other technology out there that can do what we are doing in our lab,” said Coskun, an assistant professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University. “Cells control everything in our body, and molecular bioengineering is key because we can understand tissues on the micro level.”

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The award provides Coskun with a niche community and the opportunity to exchange findings with like-minded colleagues, he said.

“Mentorship mattered a lot in this process, and I’m very grateful for the supportive people in the Coulter BME Department and at the Petit Institute of Bioengineering and Bioscience at Georgia Tech,” Coskun said. “I’m also grateful to the dedicated students in my lab. They’ve published key papers in their respective fields that have made a real impact, and their perseverance, patience,

Wallace H. Coulter Department of Biomedical Engineering

and curiosity are the major drivers of my research group.”

Coskun has been developing technology to visualize tumor molecules at the single-cell level, a much higher resolution than traditional technologies. Coskun compared his process to examining the individual fruits in a smoothie, rather than the smoothie itself. With this level of detail, he then builds a microenvironment, cell by cell, that maps the metabolic activity of the different cell types in the tumor.

Coskun and his team use this cell data in conjunction with artificial intelligence to predict, design, and eventually prescribe treatments based on an individual’s metabolic activity. The end goal, Coskun said, is to understand how different diets and lifestyles affect a patient’s response to cancer and to help their immune system become more metabolically competent.

“The unresolved challenges of medicine and why we lose our loved ones go back to these mechanisms,” Coskun said.

“If I can understand cells in their original environments and I can build environments that communicate what’s happening in their tissues, then I can contribute to healthy aging and the management of deadly diseases.” ‣ EMMA RYAN

OUR COMMUNITY

Fong awarded Disney Award for Research in Amblyopia A biomedical engineering researcher will use recently awarded grant dollars to expand research to improve the lives of individuals who deal with amblyopia, or lazy eye.

Ming-fai Fong, Ph.D., assistant professor in the Wallace H. Coulter Department of Biomedical Engineering, is a recipient of the Research to Prevent Blindness (RPB) Walt and Lilly Disney Award for Amblyopia Research to support eye research into amblyopia. The RPB granted Fong the $100,000 grant over a two-year period.

“I am thrilled to receive this prestigious award and am grateful to the Disney Family and RPB for their generous support for amblyopia research,” Fong says.

Fong will use the funds to further explore cells that can offer recovery from amblyopia, a disconnect between the brain and the eye that causes poor vision as the brain favors one eye over the other. As a result, the affected eye may wander.

Fong, along with researchers from MIT and Dalhousie University,

previously discovered that temporary silencing the retina can promote recovery from amblyopia in mice and cats beyond the classical critical period.

“The RPB Disney Amblyopia Award will allow us to identify the specific cell types in the retina that mediate this remarkable recovery in mice, and hopefully lead to more targeted clinical interventions for amblyopia in humans,” Fong explains.

Fong’s lab studies how visual experience and deprivation alter the brain from synapses and cells to circuits and systems. Her research team’s findings help develop pre-clinical interventions for treating visual and neurological disorders, as well as design assistive technology for the blind and visually impaired community.

The Disney Award was established in 2002 to strengthen and support amblyopia research. To date, the program has given awards to 31 vision scientists in departments of ophthalmology at universities across the country.

Since it was founded in 1960, RPB

has channeled more than $407 million into eye research. As a result, RPB has been identified with nearly every major breakthrough in vision research in that time. For information on RPB’s grants program, listings of RPB institutional and individual grantees, and findings generated by these awards, go to www.rpbusa.org. ‣ KELLY PETTY

Yoganathan Named 2023 AAMI Foundation Award Winner Ajit P. Yoganathan, Ph.D., Emeritus Regents’ Professor and the Wallace H. Coulter Distinguished Faculty Chair, is the recipient of the Laufman-Greatbatch Award from the Association for the Advancement of Medical Instrumentation (AAMI).

This prestigious recognition honors an individual who has made a unique and significant contribution to the advancement of healthcare technology and systems, service, patient care, or patient safety.

Yoganathan’s work has been called ‘foundational’ for the development and evaluation of numerous cardiovascular devices. He also regularly works with medical device regulatory organizations

and has influenced the development of industry-defining standards.

The award committee specifically noted Yoganathan’s work to study and evaluate more than two dozen prosthetic heart valve designs that have been implanted in the U.S. since 1975.

“I am truly honored by this award, since it recognizes my passion for impacting human lives and in ensuring safe cardiac devices for patients in need,” Yoganathan said. “This is my research philosophy: from bench to bedside, and more recently bench to bassinet - in dealing with heart valve devices for pediatric patients.”

Yoganathan received his award at the at the 2023 AAMI eXchange, June 16–19, in Long Beach, CA. ‣ KELLY PETTY

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OUR COMMUNITY

State Department Supports Student-Crafted Engineering Workshops for High School Girls Georgia Tech and Emory University undergraduates are working to expand engineering exposure to girls in metro Atlanta high schools before college.

Their goal is to help young women see the creativity and impact of engineering and get them excited about the field.

Biomedical engineering students Emily Yan and Zakir Ahmedin are drawing from their own experience as classmates in a DeKalb County public high school who came to Georgia Tech to study engineering.

“I found it difficult to transition to Georgia Tech with no engineering experience beforehand,” said Yan, who’s now in her third year. “It can be intimidating for young girls to go into engineering when they don’t know a lot about it.”

As one of the BMED 1000 Teaching Assistants, Yan was able to talk to many first-year students in the Wallace H. Coulter Department of Biomedical Engineering who shared a similar experience. The head instructor for the course, lecturer Todd Fernandez, encouraged her and provided guidance to create a project that would address this.

Yan, Ahmedin, and Emory international relations and human health student Rachel Kroger plan to close that gap, and they’ve secured a $10,000 Citizen Diplomacy Action Fund grant from the U.S. Department of State to help.

In the fall, they will partner with Georgia Tech’s Center for Education Integrating Science, Mathematics, and Computing (CEISMC) to bring high-school-age women to campus for four weekends of seminars and lectures with Georgia Tech faculty. The instruction will cover topics in mechanical, computer, and biomedical engineering, with other sessions on career development and a month-long engineering project.

They’re calling the program EDGE: Educational Development for Girls in Engineering.

“It’s exciting that Georgia Tech undergraduates are so committed to sharing their passion for engineering with their younger peers,” said Dr. Lizanne DeStefano, executive director of CEISMC. “We look forward to partnering with them on this exciting program.”

In developing the workshop approach, the team talked to DeKalb County Schools administrators. Yan said the conversation helped her realize that offering students 33

Wallace H. Coulter Department of Biomedical Engineering

more creativity and design-centered experience would be valuable. Often, she said, the engineering curriculum in Georgia public high schools is technical and based on repetition of previous engineering projects and problems instead of giving students a chance to develop their own solutions.

Ahmedin recalled his own experience taking an engineering class offered at his high school: “We were developing fundamental skills, like learning 2D drawing with AutoCAD, but there was no creativity or design in the process — unlike Georgia Tech classes.”

He said exposure to engineering is vital for inspiring prospective students.

“The biggest issue is that people don’t pursue engineering because they don’t know what it really is. Others might have a negative experience because they’re not adequately prepared for an engineering program or don’t have previous exposure to the field.”

In particular, the EDGE program will focus on young women from historically underrepresented backgrounds, who have traditionally had fewer opportunities to explore engineering and other STEMoriented fields. The group said they hope to remove those barriers through the EDGE program and help students find female mentors in engineering to build a community of resources and support.

Yan and Kroger spent the summer in South Korea two years ago as part of the State Department’s National Security Language Initiative for Youth program.

The grant they received for EDGE comes from a fund specifically for alumni of U.S. government-sponsored exchange programs.

Yan said spending the summer abroad helped them grow as more resilient leaders and gave them confidence to start EDGE. She hopes the two weekends of instruction will give young women the same boost in confidence.

“We chose to target high school freshmanto-junior-year girls because this is the time when they’re thinking about what they want to do in the future,” Yan said. “This program is a vehicle for them to see the opportunities in engineering and a way to meet mentors and students who have similar experiences.”

Ahmedin echoed that hope for personal development.

“I hope the girls will find positive role models they can look up to and instill within themselves that they can set out to do anything they want, whether that be an engineering or any other career path they chose.” ‣ AMY KIM

Top to bottom: Emily Yan, Zakir Ahmedin, and Rachel Kroger are developing a camp to bring high-school-age women onto the Georgia Tech campus to learn more about the engineering field.

OUR COMMUNITY

Jeffrey Markowitz Named 2023 Sloan Research Fellow How does electrical activity in the brain lead to action? That’s what Jeffrey Markowitz wants to find out, and the Alfred P. Sloan Foundation wants to help him answer the question.

Markowitz is one of two assistant professors from the Georgia Institute of Technology selected to receive Sloan Research Fellowships for 2023, awarded this year to 125 of the brightest young scientists across the U.S. and Canada. It is one of the most competitive and significant awards available to early-career researchers.

“This is a great honor and I’m very fortunate, because this award gives us a fair amount of freedom in the early stages of our research,” said Markowitz, based in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University.

“Sometimes, how creative you can be is defined by how flexible your support is. This award is really key as we try new, innovative things in our work.”

The Sloan Research Fellowships are often seen as a marker of the quality of an institute’s science faculty, and proof of an institution’s success in attracting the most promising early-career researchers. Since the Fellowships were launched in 1955, 47 faculty from Georgia Tech have received the honor.

In addition to Markowitz, Georgia Tech’s other 2023 fellow is Anqi Wu of the School of Computer Science and Engineering. Last year, Coulter BME program faculty member Hannah Choi was a Sloan Fellow. The most recent BME primary faculty members to earn the honor are Eva Dyer and Chethan Pandarinath in 2019, and Bilal Haider in 2018.

“I am so pleased for Jeff because he is highly deserving of the prestigious Sloan Research Fellowship,” said Coulter BME Department Chair Alyssa Panitch, who nominated Markowitz for the honor.

“This speaks well of Jeff and his amazing research, and also is a reflection of the talent and creativity that has become a part of the culture here in the Coulter Department and at Georgia Tech.”

Sloan Fellows receive a two-year, $75,000 fellowship to further their

“Sometimes, how creative you can be is defined by how flexible your support is. This award is really key as we try new, innovative things in our work.”

— JEFFREY MARKOWITZ

research. The honor is open to scholars in eight fields – chemistry, computer science, economics, mathematics, computational and evolutionary biology, neuroscience, ocean sciences, and physics. Markowitz won in the neuroscience category.

PARADIGM SHIFT In winning the fellowship, Markowitz also joins an association of towering figures in the history of science. More than 50 Sloan Fellows have received the Nobel Prize in their respective field. The list of fellows also includes winners of the National Medal of Science

and many other prestigious honors.

The Markowitz lab aims to identify the neural mechanisms that lead to action selection — basically, something that is happening every second. Every moment, beneath the surface, we take stock of our internal state and the external world and select a behavior, or an action. Even sitting still in a chair is an action.

“In a way it sounds abstract, but pretty much everything we do involves the selection of one action or another,” said Markowitz, who also won a Packard Fellowship in 2022.

Action selection is central to survival and the underlying neural circuits are key players in several neurodegenerative disorders, most prominently Parkinson’s disease. Despite decades of research, the neural mechanisms of action selection remain misunderstood, which means that more robust treatments for Parkinson’s remain out of reach.

Markowitz and his team, working in the multidisciplinary frontier of machine learning and biology, are going after nothing short of a paradigm shift.

“That will be necessary if we want to uncover the neural factors underlying action selection and unlock the next generation of therapeutics for associated neurodegenerative disorders.”

They’ve created a system that exploits the latest advances in machine learning to, in a fully automated and unsupervised way, identify stereotyped behaviors from 3D motion capture of freely behaving mice. Pairing this system with chemical lesions and neural recordings, they’ve discovered that the basal ganglia, a group of nuclei deep in the brain, play a role in controlling action selection.

“The next phase of my research will directly probe how neural activity is orchestrated in space and time to instantiate action selection as it unfolds,” said Markowitz, whose team has developed its technology in experiments with mice. “But we think that if we can really learn how the brain controls action, we’ll be able to leverage that knowledge into something impactful for humans further down the line. That’s our ambition for the future.” ‣ JERRY GRILLO

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OUR COMMUNITY

MBID Graduates Tap Into ‘Intrapreneurial” Spirit For Healthcare Solutions Improvements to cardiac care, blood testing, and surgical processes are just some of the solutions presented by the newest class of the Master of Biomedical Innovation and Development (MBID) on July 27.

The cohort completed their studies with final exam presentations of their year-long team projects that address critical healthcare issues. Faculty from the Wallace H. Coulter Department of Biomedical Engineering (BME), medical mentors, clinicians, and representatives from the medical device industry were all in attendance to assess the projects.

“These students defined relevant problems and unmet clinical needs. Then they learned how the puzzle pieces fit together in biomedical innovation and product development,” said Sathya Gourisankar, Ph.D., FAIMBE, professor of the practice MBID program director. “They’ve been given enough exposure to the process to launch their careers and get a foot in the door of industry, where they will continue their development and become experts in their fields.”

The students split into five groups and work alongside medical professionals to gain hands-on experience in the design and commercial development process typical of the medical device industry.

Ideas ranged from an early detection and screening tool to assess heart failure to a surgical stapler that replaces the conventional handoperated suturing device for septoplasty that

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Wallace H. Coulter Department of Biomedical Engineering

can prevent infections and additional surgeries.

“I love the fact that some of the teams are taking on extremely challenging problems with a higher risk,” Gourisankar.

“They are encouraged to pursue what they want.

We (the faculty) are here to offer our two cents, but it’s up to the students to give a good rationale for what they’ve developed.”

Now in its 10th year, the MBID program has produced 266 graduates, with the 2022-23 cohort being the first to complete all coursework in BME’s U.A. Whitaker Building, according to Gourisankar.

“This cohort had the unique challenge of being the first on Georgia Tech’s main campus since the beginning. And there have been challenged in terms of facilities and resources,” Gourisankar said. “They had 11 months to make things happen, to find a process, to build a relationship and come to the agreement that all the teams need to do well.

They showed great ability to be “intrapreneurial,” not just entrepreneurial — intrapreneurial, meaning using the resources within their environment to get the job done.” ‣ KELLY PETTY

Above: Derek West, MBID student and Neurosure project leader, presents a non-invasive method to monitor and prevent position related nerve injuries during surgery.

(PHOTOS: JERRY GRILLO)

OUR COMMUNITY

NSF Recognizes Kelly Cross for Her Work in in Engineering Education Kelly J. Cross is a self-identified preacher’s kid. Her work is her ministry, and she’s using her research as a pulpit to amplify the voices of people in engineering with marginalized identities.

As an assistant professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, Cross aims to change the culture of engineering education, prioritizing diversity, equity, and inclusion. And now, the National Science Foundation is supporting her efforts with a Faculty Early Career Development Award, or CAREER Award. The five-year grant is designed to help promising researchers establish a foundation for a lifetime of leadership in their field.

“For me, it is recognition of the quality and value of my work so far, and the result of years of hard work and difficult conversations to move the field of engineering forward,” said Cross, who shifted gears as a student, changing her focus from chemical engineering to engineering education. “Equity, empathy, and excellence — the E3 — are core components of all my work as a researcher and scholar for supporting these conversations in engineering.”

According to Cross, when we start with empathy, we can create an equitable engineering environment that will lead to inclusive excellence and the development of holistic solutions to complex problems.

Specifically, highlighting inequity in student experiences has been a consistent theme in Cross’s multiple projects that focus on different marginalized groups.

For instance, she has researched and published on challenges unique to women of color in engineering. And in 2021, she led a group of STEM profes-

sionals to describe experiences being, or supporting, the queer identified in engineering in her book Queering STEM Culture in U.S. Higher Education.

Empathy is integral to her research, which emphasizes the voices of participants who critique the culture, rather than blame the students. And Cross intentionally strives for excellence in all of her research and scholarship — her papers on African American men and student stress are being used as exemplars in their field.

“The CAREER Award is a foundational grant for my lab, supporting my research and teaching philosophies, helping me continue to train the next generation of engineering education researchers,” said Cross. “It also provides credibility for my trainees and maintains the standard of excellence in research established within my department and the College of Engineering at Georgia Tech.”

But Cross is aiming to create impact beyond university campus borders.

Her research can also be applied in government agencies and industry groups that are trying to address diversity, equity, and inclusion (DEI) issues. She provides online and in-person faculty and professional development workshops focused on culturally responsive teaching, managing personal bias in science, technology, engineering, and math (STEM), and timely topics, such as mitigating power and privilege in the classroom.

Cross will use the CAREER Award to create a more efficient approach to training engineering faculty through development of GIVEN — Gaming Intervention of Values Engineers Need.

The online gaming tool will track the evolution of engineering faculty beliefs about diversity, and the research team

“Equity, empathy, and excellence — the E3 — are core components of all my work as a researcher and scholar for supporting these conversations in engineering.”

— KELLY CROSS

will assess the impact of the tool with both surveys and individual interviews.

“The aim of the gaming tool study is to increase the engineering faculty engagement with DEI efforts, increasing our understanding of strategic approaches for broadening participation and how faculty can effectively teach diverse students in STEM,” said Cross, who is particularly proud of the book that she had published last year.

Queering STEM Culture, released in June 22, was edited by Cross, Stephanie Farrell, and Bryce Hughes. The book explores the experiences of members of the LGBTQ+ community in post-secondary STEM culture, providing critical insights into progressing along socially just educational pathways. Since its release, Cross has been contacted by numerous students who have written to tell her that reading the book, “made them feel seen,” Cross said.

There is both a professional and deeply personal relevance to that kind of feedback for Cross.

“Identity has played such a significant role over the course of my life,” said Cross.

“As I started my engineering education PhD, I learned that here was an entire field of study. And one of the goals of my career is to show how identity is related to engineering education.” ‣ JERRY GRILLO

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Sanger Sequencing Initiative Offers In-House Alternative For Sample Testing Most biological research is grounded in DNA sequencing, a way to determine the order of organic molecules in DNA. The process is typically conducted by large-scale biotech companies, but the drawbacks can be time, cost, and environmental impact.

Georgia Tech’s Molecular Evolution Core (MEC) has solved that problem for Tech researchers through its Sanger Sequencing Initiative (SSI), which offers the same service conveniently on campus.

“What makes a researcher or a lab want to switch over to us? We provide the same if not superior-quality data to them,” says Nicole Diaz, SSI’s founder and manager, and a fourth-year student in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University. “We use an optimized process that is less industrialized. And the service we offer is more personal, so if researchers have any issues, we are able to be a lot more flexible than the big companies.”

Launched in 2020, SSI has evolved into a full-fledged, student-run program to collect and process samples for research labs.

Researchers can submit samples in drop boxes at one of six locations in the BioQuad — Krone Engineered Biosystems

Building, Molecular Sciences And Engineering, Ford Environmental Science & Technology Building, Marcus Nanotechnology Research Center, Cherry L. Emerson Building, and the Parker H. Petit Institute for Bioengineering and Biosciences at Georgia Tech.

Samples are charged at $5 per tube for less than 20 samples. That price is reduced to $4 per tube with more than 20 samples. After 96 samples are processed, the price goes down to $3.50 per tube.

And with just three billing cycles based on the academic calendar — fall, spring, and summer — labs can easily reach the lowest discounted price for all samples by the end of the semester regardless of how many samples are submitted at a time, Diaz says.

Turnaround time is within three days.

The added benefit of working directly with SSI is its commitment to providing a sustainable sampling process.

“The carbon footprint is lowered by keeping samples local instead of shipping them across the country to have them sequenced,” Diaz says. “So, researchers have access to dropboxes just outside the door of their lab in the buildings here in the BioQuad.”

Lab technicians are culled from federal work study, student

assistants, student volunteers, or those seeking internship credit.

“It’s great to have a foundation and building blocks where I won’t be nervous when I encounter this down the road,” says, Aaron Kent, a first-year chemical engineering student.

SSI not only services labs at Georgia Tech, but it can also support labs for institutions in the Georgia Research Alliance, a consortium of public and private universities in Georgia including Emory University, Morehouse School of Medicine and the University of Georgia.

A NOVEL IDEA DURING COVID-19 Sanger sequencing has been conducted in the Molecular Evolution Core (MEC) since 2018 under the direction of research technologist Naima Djeddar.

Anton Bryskin, Regents researcher and MEC technical director, wanted to expand the mission of the MEC and tap into an undervalued resource on campus — undergraduate students.

“I knew that undergraduate students at Georgia Tech are very special,” Bryskin says. “It was never thought that undergraduate students might do a part of the work typically done by researchers or technicians.”

With support from M.G. Finn, professor and chair in the School of Chemistry and Biochemistry and chief advisor of the MEC, the Sanger SequencTop: SSI founder and fourth-year biomedical engineering student Nicole Diaz shows how samples are kept in cold storage in the Sanger lab. (PHOTO: KELLY PETTY) Left: DNA samples are loaded into the Sanger Sequencing processing machine. (PHOTO: KELLY PETTY)

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Wallace H. Coulter Department of Biomedical Engineering

OUR COMMUNITY ing Initiative (SSI) was launched in 2020. The height of Covid-19 proved to be a valuable time for the program.

Between sample processing sessions for Tech’s Covid-19 surveillance testing program, student workers were pulled to process sequencing samples for SSI. “It was great because these students had already been trained on clinical practices,” Diaz says. “So, we didn't have to go back and train them on what it would be like in the lab because they already had the maximum training that was necessary.”

Diaz joined the Initiative in its inception as a federal work study student. Since then, she’s led the growth and development of SSI, from processing samples to marketing to hiring to building out a lab management system for operations alongside operations manager of the MEC TipCycling program and fourth-year biomedical engineering student Helya Taghian.

Not only have undergraduate students gained valuable lab experience, Diaz said, but SSI has become a multidisciplinary effort. The staff is composed of students from biomedical, industrial, and chemical and biomolecular engineering, as well as computer science and design majors.

“We have a stacked team,” she says.

Diaz says the team is working to incorporate more automation into the process, including tracking metrics for sample processing and developing a bioinformatics solution to optimize workflow and data quality. Third-party app integration to centralize the SSI workflow was tackled by the MEC web development team — comprised of computer science (CS) undergraduates led by fourth-year CS student Bakr Redwan — whom devised a custom Laboratory Information Management System (LIMS). This LIMS system will serve as SSI’s hub for all operations including processing, billing, inventory, and communications.

SSI currently processes samples for several labs across campus, including for Finn, Chemical and Biomolecular Engineering Professor Mark Styczynski, and newly elected National Academy of Engineering Professor Mark Prausnitz, and hopes to expand to more labs in the future.

“We want to be an example program for other universities to use, implement in different capacities, and offer the same opportunities to their undergraduate students,” Diaz says. ‣ KELLY PETTY

Haynes, Qiu Inducted into the 2023 Class of the AIMBE College of Fellows Two faculty members in the Wallace H. Coulter Department of Biomedical Engineering have being named to the American Institute for Medical and Biological Engineering (AIMBE) College of Fellows.

Associate Professors Karmella Haynes and Peng Qiu were inducted along with 140 colleagues who make up the AIMBE College of Fellows Class of 2023 at a formal induction ceremony held during the AIMBE Annual Event on March 27 in Arlington, Virginia.

Haynes was recognized by peers and members of the College of Fellows “for inventing epigenome actuation, a new approach for epigenetic engineering, and outstanding contributions to bioengineering education, and diversity and inclusion.”

"To be recognized by such a prestigious organization as AIMBE is not only a personal honor, but also an opportunity to inspire and Karmella Haynes (top) and Peng Qiu. encourage the next generation of scientists and engineers, particularly those who come from historically marginalized backgrounds," "engineering and medicine research, Haynes said. "I hope that this recogpractice, or education” and to "the nition will catalyze greater diversity, pioneering of new and developing equity, and inclusion in the field, fields of technology, making major and that it will encourage others advancements in traditional to pursue their passions and make fields of medical and biological meaningful contributions to society." engineering or developing/impleQiu was nominated College of menting innovative approaches Fellows members and peers “for to bioengineering education." outstanding contributions in While most AIMBE Fellows bioinformatics, computational hail from the United States, the biology, and single-cell data science.” College of Fellows has inducted “It is a great honor to be Fellows representing 30 countries. elected and recognized for my AIMBE Fellows are employed research work,” Qiu said. “AIMBE in academia, industry, clinical provides not only a wonderful practice and government. network to connect with leading AIMBE Fellows are among the researchers, but also opportunities most distinguished medical and to reach out to non-academics.” biological engineers including 3 Election to the AIMBE College Nobel Prize laureates, 17 Fellows of Fellows is among the highest having received the Presidential professional distinctions accorded Medal of Science and/or Technology to a medical and biological engineer. and Innovation, and 205 also The College of Fellows is comprised inducted to the National Academy of the top two percent of medical of Engineering, 105 inducted to and biological engineers. College the National Academy of Medicine membership honors those who have and 43 inducted to the National made outstanding contributions to Academy of Sciences. ‣ KELLY PETTY Fall 2023 Magazine

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Tip Cycle Program Aims to Reduce Single-Use Plastics in Campus Labs Environmental scientists have spent the last few years sounding the alarm on the growing single-use plastic waste problem plaguing landfills. Consumer-based products like plastic bags, straws and water bottles are often named as culprits, but inside laboratories across the country, researchers are faced with their own single-use plastic dilemma — pipettes.

A single lab can discard an average of 36,000 pipettes each year. Georgia Tech is addressing the problem with a solution that focuses on reuse of this critical lab tool through its Tip Cycle program.

“This does not come from the traditional recycling method; the tips are not manipulated or changed,” says Adam Fallah, project manager for the program. “It’s more reuse versus recycle.

The life cycle of the pipette is lengthened.”

Housed in the Molecular Evolution Core (MEC) of the Parker H. Petit Institute for Bioengineering and Biosciences (IBB), the Tip Cycle program is capable of washing unfiltered pipettes to allow for multiple uses before discarding them.

MEC purchased the pipette washing technology from laboratory equipment supplier Grenova in 2020.

Typically, a research lab will purchase hundreds of boxes of pipettes, use them once, and then throw them away. This cycling program eliminates that waste and cost by reusing the pipettes.

So far, Fallah says the team has washed more than 746,000 pipettes in the last year, saving the equivalent of five tons of plastic going to waste.

Grenova’s technology is similar to a laundry washer and dryer—used pipettes are set in a tray and loaded into a washer to go through several cycles before being dried, repackaged, and sent back to a lab. The cycles include multiple-high heat rinses, UV sterilization, and sonification, which uses sonic waves to disturb any residue, like proteins, in the pipette tips.

Fallah says he uses an in-house cleaning solution and can customize it with a 5% bleaching solution if requested by a lab.

The full processing time for four boxes of tips

Operations manager and is two hours and eight minutes. Roughly every fourth-year biomedical 25-30 minutes another round of cycling begins engineering student Helya as the boxes of tips are rotated out. Pipettes Taghian examines clean are returned to clients within 2 to 3 days. pipette tips to maintain “We can pump out 40 boxes in 5 to 6 hours a quality control. (PHOTO: KELLY day,” says Helya Taghian, operations manager and PETTY) a fourth-year student in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University. “We do 60 to 70 wash cycles of 200 to 300 boxes of tips a month. It would be a money sink if you bought that many tips…you have to be a pretty big lab to go through that many tips.”

Like the Sanger Sequencing Initiative, the Tip Cycle program was conceptualized at the height of Covid-19. Pipette supply was in shortage at the time and the IBB had just purchased the pipette washing equipment. Fallah was tasked in the fall of 2020 by then-principal research engineer Mike Shannon to set up and facilitate a workflow for the instrument.

Principal research scientists Mike Shannon and Mike Farrell, along with Regents researcher and MEC technical director Anton Bryksin, called an emergency meeting to come up with a solution.

Bryksin devised an unconventional idea of washing the tips, a risky move given the sensitivity of qPCR techniques that can detect

Typically, a research lab will purchase hundreds of boxes of pipettes, use them once, and then throw them away. This cycling program eliminates that waste and cost by reusing the pipettes.

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Wallace H. Coulter Department of Biomedical Engineering

OUR COMMUNITY

even a single molecule of RNA/DNA. Washing all the tips together also posed the potential for spreading contamination rather than eliminating it.

The Tip Cycle program garnered support from IBB and its assistant director, Michelle Wong, who recognized the potential for the project to help the university achieve its environmental sustainability goals.

Bryksin spearheaded the design of the program’s validation protocols, while Fallah took charge of implementing and organizing a student team to support the effort.

The team encountered numerous hurdles in perfecting the washing process to ensure the tips were completely free of contamination, all while validating the washing protocol to maintain the accuracy of the qPCR results.

Bryksin says the program's initial success was nothing short of remarkable. It not only allowed the testing laboratory to continue processing Covid-19 samples, but also provided an environmentally conscious alternative that substantially reduced the amount of plastic waste generated by the lab.

As a result, the Institute recognized the potential of the Tip Cycle program and provided funding for its further development and enhancement.

At the same time, Taghian was one of several students supporting the Covid-19 surveillance testing program.

“There was a dark corner in the lab and my curiosity sent me there to see what Adam was doing,” she recalls. Initially, she spent much of her time helping Fallah rack pipette tips to be placed in the machine.

Eventually, she teamed up with Fallah to take the lead on developing an operational process for the program.

“I learned a lot of things about optimization,” Taghian says. “I was having a lot of fun and there was a lot of innovation in it.”

Taghian worked with fellow biomedical engineering student and program manager of the Sanger Sequencing Initiative, Nicole Diaz, to hire students for the Tip Cycle program.

Other aspects of the program began to fall in place. Data management charts and a workflow management board helped to keep operations running optimally. The duo also hired an industrial design major to create branding and a website.

“We want this to be educational,” Taghian says. “No matter what your major you can gain industry experience while doing your research. You’re dealing with vendors and actual instruments in a business environment. At the same time, your major has a place to shine.”

SCALING UP FOR THE FUTURE Currently, the Sanger Sequencing Initiative and labs run

by Associate Professor Kirill Lobachev and Professor M.G. Finn in the College of Sciences utilize the Tip Cycling program. Fallah says he is in talks to bring on another lab and looks to partner with teaching labs in the School of Biological Sciences to educate more students about single-use plastics in laboratories.

Fallah also wants to devise a plan to wash pipette tip plates, as well as find other ways to reuse the plastic inserts and boxes the pipettes are delivered in. The hope is to get as close to zero-waste with the program.

“Very few research institutions have a core facility with in-house services and in-house researchers assisting labs across campus,” Taghian says. “An environment exists on our campus where students can get an opportunity to explore an industry field without going off campus Fallah says researchers are often “creatures of habit” and may gawk at the idea of reusing pipettes over fears of cross-contamination. But he stands by the efficacy of tip cycling as a sustainable way to manage pipette use and alleviate supply chain issues.

“We’re in a prime position right now to be a pioneer and change the future of labs.” ‣ KELLY PETTY

TipCycle project manager Adam Fallah demonstrates how Grenova's pipette tip washing system operates. (PHOTO: KELLY PETTY)

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Two Teams Win Top BME Prize in Capstone Expo Teams AdvanCED and Jawws tied for Best BME Project during the Spring 2023 Capstone Expo.

Pictured with Buzz and Dr. James Stubbs, professor of practice and director of the Global Health Capstone.

(PHOTO: CANDLER HOBBS)

Two projects designed to help clinicians operating on the human skull won best project awards in the Wallace H. Coulter Department of Biomedical Engineering at the Capstone Expo, Tuesday at McCamish Pavilion on the Georgia Tech campus.

A team of four BME students called AdvanCED, sponsored by the Mayo Clinic, developed an implantable device for the safe, efficient delivery of cell therapies to the brain to treat brain tumors.

And a team of five women called Jawws designed a tool for maxillofacial surgeons to measure the correct screw length for mandibular bony fixations, designed to minimize post-operative complications.

Also, for the first time there was a shout-out for honorable mention teams from each department or school. In BME, the five-person team of PAD

Sara Farnoli of team Stealthoscope showcases an innovative, condensed stethoscope for military healthcare personnel operating in the field.

(PHOTO: KELLY PETTY)

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Wallace H. Coulter Department of Biomedical Engineering

Screen earned honorable mention for their portable automatic screening device to detect early onset peripheral arterial disease. The tool uses bioimpedance analysis technology and can assist physicians with providing patients a recommendation for further diagnosis.

A male student shows a model of three different stages of arterial disease as part of his team's capstone project. Another male student stands behind him near a poster presentation board.

Team PAD Screen earned honorable mention for their portable screening device that detects early onset peripheral arterial disease.

“The challenge was being able to actually see the problem, and we had the privilege of actually observing the conditions in a Grady surgical room,” said Ruiyang Zhao, one of the Jawws team members. Her teammates were Qingyu Chen, Xinyu Chen, Yunha Ham, and Yunseo Ham. Meanwhile, AdvanCED addressed the problem of administering cell therapies to patients with glioma, a wide-ranging kind of brain tumor that includes glioblastoma, which is highly malignant and typically requires surgical removal, chemotherapy, and radiation. Because these tumors usually are not completely removed, there is a 90% recurrence rate. While implantable devices currently exist for the delivery of therapeutics, there is no such thing for the delivery of advanced cell therapies to the brain for gliomas.

“Initial administration of the cells is done in the operating room the first time they cut the tumor out,” said Mateo Golloshi, whose teammates on

OUR COMMUNITY

AdvanCED are Isabella Varea, Juan Martinez, and Victoria Kabat. “If another dose is required, they have to open up the patient again. Neurosurgeons currently don’t have a recurrent, minimally invasive option to administer the cell therapy.”

So, the team developed LifeSTEM, which uses a multi-chamber reservoir for the targeted, local delivery of cell therapies, with a guiding sleeve and customizable catheters, to account for the variability of tumor location and patient anatomy.

In all, there were 191 teams of undergraduate students throughout the arena, including 31 BME teams, taking part in the Expo. BME students addressed the usual dizzying array of problems with creative solutions. Stealthoscope developed a condensed stethoscope for military healthcare personnel operating in the field. Insight created an illuminated nasal speculum that allows for increased visi-

Team PAD Screen earned honorable mention for their portable screening device that detects early onset peripheral arterial disease. (PHOTO: KELLY PETTY)

bility into the nasal cavity. Hassle-Free TSA optimized a patient-specific implant to treat severe shoulder wear and tear. And a team called Eye.See.U developed a contact lens applicator for people with quadriplegia.

Every semester, the Capstone Expo showcases senior engineering student projects designed to solve a specific challenge or problem, and for many students, it’s a sample size of the future.

“Capstone has been like a microcosm of what to expect if you design products and devices for the healthcare industry,” noted Adam Sumilong of the Eye.See.U team. “It’s great foundational training.” ‣ JERRY GRILLO

Astros Fellowship Sends Azalia Cyphers to Women in Sports Data Symposium Undergraduate Azalia Cyphers finally will be able to merge her passions for biomedical engineering and sports at the Women in Sports Data Symposium in late August, courtesy of the Houston Astros.

The Major League Baseball team has selected Cyphers for an inaugural Women in Sports Data Fellowship, supporting her attendance at the symposium in Brooklyn and giving her the “very rare opportunity of pursuing my interests and dreams,” according to the third-year student in the Wallace H. Coulter Department of Biomedical Engineering.

“It was already surreal discovering the Women in Sports Data initiative and how MLB really wanted to pour into women that aspire to work in technical roles through the fellowship, so to be selected felt like a dream come true,” Cyphers said. “I was inspired by the women behind the scenes of professional sports. As a former athlete and manager for my high school baseball team, I’ve always wanted to examine the intersection of biomedical engineering for injury prevention and recovery.”

Cyphers also is a Georgia Tech College of Engineering Clark Scholar, a signature academic program combining engineering, leadership, and community service. She has been on the lookout for ways to blend her athletic background and her engineering education. When she started to learn how to find and use measurable data to create healthcare solutions in courses like Problems in Biomedical Engineering and Conservation Principles, she saw how biomechanics tools and techniques can help researchers, trainers, and athletes use data to optimize performance and recovery.

Since May, Cyphers has been working on a research project developing devices to collect data from Georgia Tech athletes that could help them prevent injuries and promote recovery. At the symposium, she said she’s eager to meet with the Astros research and development team to talk to them about her ideas, get feedback, and formulate her next steps.

Those conversations are just one of the opportunities Cyphers said she’ll have to connect with other women who share her interest in helping athletes with actionable data.

“I am hoping to get guidance and greater insight from women working in technical roles, especially regarding data science and the use of biotechnology in baseball,” Cyphers said. “I am also looking forward to networking with peers who have their own sports data dreams and goals, and to be on the forefront of impactful change in the professional sports industry.” ‣ JOSHUA STEWART

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OUR COMMUNITY

Eight BME Faculty Receive Promotion and Tenure The spring 2023 cohort of faculty members in the Wallace H. Coulter Department of Biomedical Engineering who received tenure and promotion were recognized for their significant contribution to scholarship, research, and teaching, as well as their commitment to their institution’s mission.

Promotion to Associate Professor with Tenure

ERIN BUCKLEY

CHETHAN PANDARINATH

EVA DYER

SHU JIA

CASSIE MITCHELL

ANNABELLE SINGER

Promotion to Professor with Tenure

PENG QIU

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Wallace H. Coulter Department of Biomedical Engineering

BILAL HAIDER

OUR COMMUNITY

New Faculty The Wallace H. Coulter Department of Biomedical Engineering welcomed two new faculty members for the 2022-2023 academic year. Both hires bring extensive experience in career advancement and diversity, equity, and inclusion, and reflect the department's commitment to preparing students for the workplace through professional development and soft skills training.

WENDY COCKE Professor of the Practice Wendy Cocke teaches some of the critical foundational design courses for Coulter BME undergraduate students. But what she really teaches them is how work works. That’s what she tells friends when they ask about her job in Coulter BME. “Historically, we tend to teach biomedical engineering students about how to go into research and development,” said Cocke, who spent 20-plus years gaining practical experience in the medical device industry after graduating from Georgia Tech and has led multiple teams in various phases of design and development. “Quite frankly, R&D jobs look a lot like academia. I’d like to help our students understand the breadth of jobs that are available to them so that they can be thinking about or applying themselves toward for the ones that they don't even know exist.”

It also would not be a big stretch to say that she literally wrote the book on flexible thinking when it comes to work: Cocke’s first book, Making Flex Work: Defining Success on Your Own Terms, was released in July 2022.

RACHAEL S. PITTS HALL Director of Faculty and Student Training Trained as a chemist, researcher, scientist, and educator, Rachael Pitts Hall has become a great communicator along the way, translating complex science across disciplines to the public and colleagues. Pitts Hall is now putting their combination of skills and enthusiasm to work as director of faculty and student training for Coulter BME, where they are training and assisting grad students and faculty in inclusive teaching and mentoring. They also coordinate the Art of Telling Your Story (BMED 4000), mentoring new instructors for the class.

“The best part of my job is getting to know the students and then advocating for their needs,” Pitts Hall said.

“All of our PhD students take my class, BMED 7004 and 7005, and I'm very honored and happy to get to be part of their development and to help mold the experience to support them as individuals. Also, all undergrads now take 4000, so I get to learn about them and help them package their experiences at Georgia Tech to advocate for themselves and their ideas. We have fantastic students and getting to work with and mentor them is just awesome.”

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Commercialization TAKING BIOMEDICAL INNOVATION FROM THE LAB AND INTO THE MARKETPLACE

New Company From BME Tech Improves Blood Cell Analysis Before patients can begin a regimen of some critical treatments — like a life-saving round of chemotherapy — they must undergo a hematological analysis.

This prerequisite blood test involves a complex roadmap of expensive equipment, not to mention the trained personnel to calibrate, maintain, and use it, plus multiple reagents, and finally, time to test the sample in a specialized lab.

The process can take hours or anxious days, delaying the administration of a treatment. That’s how it usually works.

But a new company spun out of innovative research in the Coulter Department aims to eliminate those delays.

Cellia Science, Inc., is creating point-ofcare hematology analyzers based on the innovative ultraviolet (UV) microscopy system developed in the lab of Associate Professor Francisco Robles, who serves as the company’s chief science officer.

Built with funding from VIC Technology Venture Development, Cellia’s first device will be designed to help chemotherapy patients at risk of neutropenia (when a patient has too few neutrophils, infection-fighting white blood cells) or thrombocytopenia (a low blood platelet count).

“These are life-threatening conditions that can alter a treatment plan and they need to be addressed immediately,” said Robles, whose lab had been developing advanced UV microscopy technology for years but hadn’t really focused on a

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Above: Francisco Robles.

Right: Human blood cells under a microscope. (PHOTO: ENVATO ELEMENTS)

Wallace H. Coulter Department of Biomedical Engineering

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Wilbur Lam (PHOTO: JERRY GRILLO)

precise application, until now. “Because if a patient isn’t healthy enough to begin their actual cancer treatment, that will pause the care plan, which can cause negative downstream effects.”

The emphasis on white blood cell differential testing and platelet counts grew out of Robles’ collaboration with Professor Wilbur Lam, a BME faculty member and part of Emory’s Department of Pediatrics, and a physician in the Aflac Cancer and Blood Disorders Center of Children’s Healthcare of Atlanta.

“We looked at many applications for our system, but after working with Dr. Lam and researching the needs of clinicians about where a device would really have the most immediate impact, we started moving directly toward this space,” Robles said.

When cancer patients’ neutrophil counts are low and they develop a fever, they’re at risk of developing a life-threatening infection and time is not on their side.

“The capability to easily monitor neutropenia in cancer patients at the point-of-care can be game-changing,” said Lam, whose own lab has developed affordable point-of-care technology for blood disorders, often employing a patient’s own smartphone.

The Robles team introduced the technology that would spawn Cellia two years ago in a study that describes a novel, label-free optical assay sidesteps the limitations in the current standard of care, providing analysis of tens of thousands of live cells in minutes, instead of waiting for days, without any sample preparation.

Essentially, they had merged two different tests — a complete blood count (CBC) and microscopic analysis — into one. The plan is to combine them into something small, compact, portable, affordable, and easy to use, at first by caregivers in the clinic or even at your local drugstore, but eventually by patients themselves at home.

“The UV microscopy system developed in Robles’ lab has the potential to revolutionize how blood cells are analyzed and imaged and can lead to groundbreaking diagnostic technologies that will directly impact patients’ lives,” Lam said. “This technology has the potential to not only improve the quality of life of cancer patients but decrease mortality as well.”

Initially, the device would be built and marketed for a range of clinical settings, including the corner drugstore.

“It is definitely within reach that your lab or pharmacy tech will be able to do the finger prick and load the device with a blood droplet and administer

the test,” Robles said. “We only use one microliter of blood and from that we’re able to make a diagnosis very well. It’s fast, reliable, and quantitative. Our device has the potential to simplify and improve hematological analysis right there in the clinic and eventually, at home, where parents will be able to monitor their own blood counts.”

The technology’s pathway toward commercialization went through the Phase Zero Program in the Global Center for Medical Innovation, or GCMI, which is a Georgia Tech affiliate. This was the key to linking up with VIC Technology Venture Development — GCMI Director of Scientific Affairs, Evan Goldberg, is also a senior VIC fellow.

VIC has licensed the technology exclusively through Georgia Tech’s Office of Technology Licensing. The venture firm has installed Kelly Mabry, VIC’s executive-in-residence and a former VIC fellow, as Cellia’s chief executive officer. Lam is onboard serving as chief medical officer.

“This is my first company,” Robles said.

“The support from GCMI has been critical, and Wilbur has started a few companies.

So, I’ve been surrounded by real experts when it comes to the commercialization aspects of this journey. The hope is that, before too long, this technology will be available to help patients.” ‣ JERRY GRILLO Fall 2023 Magazine

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BioSpark Labs Igniting Innovation for Biotech Startups Ryan Lawler realized early on in her academic career that a scientist with a great idea can potentially change the world.

“But I didn’t realize the role that real estate can play in that,” said Lawler, general manager of BioSpark Labs — the collaborative, shared laboratory environment taking shape at Georgia Tech’s Science Square.

Sitting adjacent to the Tech campus and formerly known as Technology Enterprise Park, Science Square is being reactivated and positioned as a life sciences research destination. The 18-acre site is abuzz with new construction, as an urban mixed-use development rises from the property.

Meanwhile, positioned literally on the ground floor of all this activity is BioSpark Labs, located in a former warehouse, fortuitously adjacent to the Global Center for Medical Innovation (GCMI).

BioSpark exists because the Georgia Tech Real Estate Office, led by Associate Vice President Tony Zivalich, recognized the need of this kind of lab space. Zivalich and his team have overseen the ideation, design, and funding of the facility, partnering with Georgia Advanced Technology Ventures, as well as the Coulter Department and the core facilities of the Petit Institute for Bioengineering and Bioscience at Georgia Tech.

“We are literally in the middle of a growing life sciences ecosystem, part of a larger vision

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Wallace H. Coulter Department of Biomedical Engineering

$6M renovation

17,000 total square feet in the expanded facility

11 new labs

5

new equipment rooms with...

$1.5M in shared life sciences research equipment

Ryan Lawler

in biotech research,” said Lawler, who was hired on to manage the space, bringing to the job a wealth of experience as a former research scientist and lab manager with a background in molecular and synthetic biology.

RESEARCHERS’ ADVOCATE BioSpark was designed to be a launch pad for high-potential entrepreneurs. It provides a fully equipped and professionally operated wet lab, in addition to a clean room, meeting and office space, to its current roster of clients, five life sciences and biotech startup, a number certain to increase — because BioSpark is undergoing a dramatic expansion that will include 11 more labs (shared and private space), an autoclave room, equipment and storage rooms.

“We want to provide the necessary services and support that an early-stage company needs to begin lab operations on day one,” said Lawler, who has put together a facility with $1.7 million in lab equipment. “I understand our clients’ perspective, I understand researchers and their experiments, and their needs, because I have firsthand proficiency in that world. So, I can advocate on their behalf.”

CO2 incubators, a spectrophotometer, a biosafety cabinet, a fume hood, a -80° freezer, an inverted microscope, and the autoclave are among

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the wide range of apparatus. Plus, a virtual treasure trove of equipment is available to BioSpark clients off-site through the Core Facilities of the Petit Institute for Bioengineering and Bioscience on the Georgia Tech campus.

“One of the unique things about us is, we’re agnostic,” Lawler said. “That is, our startups can come from anywhere. We have companies that have grown out of labs at Georgia State, Alabama State, Emory, and Georgia Tech. And we have interest from entrepreneurs from San Diego, who are considering relocating people from mature biotech markets to our space.”

GROUND FLOOR COMPANIES Marvin Whiteley wants to help humans win the war against bacteria, and he has a plan, something he’s been cooking up for about 10 years, which has now manifested in his startup company, SynthBiome, one of the five startups based at BioSpark Labs.

“We can discover a lot of antibiotics in the lab but translating them into the clinic has been a major challenge — antibiotic resistance is the main reason,” said Whiteley, professor in Georgia Tech’s School of Biological Sciences. “Something might work in a test tube easily enough and it might work in a mouse. But the thing is, bacteria know that mice are not different, and they act differently in mice than in humans.”

SynthBiome was built to help accelerate drug discovery. With that goal in mind, Whiteley and has team set out to develop a better, more effective preclinical model. “We basically learned to let the bacteria tell us what it’s like to be in a human,” Whiteley said. “So, we created a human environment in a test tube.”

Whiteley has said a desire to help people is foundational to his research. He wants to change how successful therapies are made. The same can be said for Dr. Pooja Tiwari, who launched her company, Arnav Biotech, to develop mRNA-based therapeutics and vaccines.

Arnav Biotech also serves as a contract researcher and manufacturer, helping other researchers and companies interested in exploring mRNA in their work.

“There are only a handful of people who have deep knowledge of working in mRNA research, and this limits the access to it,” said Tiwari, a former postdoctoral researcher in Coulter BME. “We’d like to democratize access to mRNA-based therapeutics and vaccines by developing accessible and cost-effective mRNA therapeutics for global needs.”

Arnav — which has RNA right there in the name — in Sanskrit means ‘ocean.’ An ocean has no discernible borders, and Tiwari is working to build a biotech company that eliminates borders in equitable access to mRNA-based therapeutics and vaccines.

With this mission in mind, Arnav is developing mRNA-based, broad-spectrum antivirals as well as vaccines against pandemic potential viruses before the next pandemic hits. Arnav has recently entered in a collaboration with Sartorius BIA Separations, a company based on Slovenia, to advance their mRNA pipeline. While building its own mRNA therapeutics pipeline, Arnav is also helping other scientists

explore mRNA as an alternative therapeutic and vaccine platform through its contract services.

“I think of the vaccine scientist who makes his medicine using proteins, but would like to explore the mRNA option,” Tiwari posits. “Maybe he doesn’t want to make the full jump into it. That’s where we come in, helping to drive interest in this field and help that scientist compare his traditional vaccines to see what mRNA vaccines looks like.”

Left: Pooja Tiwari launched Arnav Biotech.

Below: Georgia Tech researcher Marvin Whiteley launched SynthBiome, which is based at BioSpark Labs.

She has all the equipment and instruments that she needs at BioSpark Labs and was one of the first start-ups to put down roots there. So far, it’s been the perfect partnership, Tiwari said, adding, “It kind of feels like BioSpark and Arnav are growing up together.” ‣ JERRY GRILLO

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COMMERCIALIZATION

Biolocity's Groundbreaking Projects Pave the Way for Medical Innovation In a bold stride toward revolutionizing medical technology, Biolocity, the philanthropic juggernaut supporting early-stage medical innovations at Emory University and Georgia Institute of Technology, has announced its latest cohort of projects for the 2023-2024 period.

With an impressive track record of awarding $10.3 million across 67 innovative projects since its inception in 2015, Biolocity continues to be a beacon of hope for cutting-edge medical technologies.

Leading the charge is Cellcue Bio, a brainchild of the brilliant minds at Emory University and Georgia Tech. This project introduces a 3D microfluidic platform that promises to redefine the landscape of cell therapies. By harnessing the power of advanced microfluidic technology, Cellcue Bio aims to enhance the predictability of clinical outcomes, ushering in a new era of personalized medicine and regenerative therapies.

With Andrés García, Ph.D., and Wilbur Lam at the helm, this endeavor is poised to reshape the future of healthcare.

Mageia Therapies, spearheaded by the visionary John Blazeck, Ph.D. of Georgia Tech, is a beacon of hope for cancer patients worldwide. This project delves into the world of immunosuppression reversal in solid tumors. Through a profound understanding of immunology and oncology, Mageia Therapies targets a pivotal signaling pathway, unlocking the immune system's full potential in combating various solid tumor types.

This breakthrough approach heralds a new dawn in cancer immunotherapy, promising renewed hope for countless lives.

The Next-Gen 5-FU project, a collaborative effort led by the brilliant minds of Emory University, presents a safer The OZ-Link leadership team includes Professor M.G. Finn, Wenting Shi, Kasie Collins, Jasmine Hwang, and Steve Seo. (PHOTO: JERRY GRILLO)

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Wallace H. Coulter Department of Biomedical Engineering

and more effective alternative to 5-fluorouracil-based therapeutics. With Dennis Liotta, Ph.D., Eric Miller, Ph.D., Nicole Pribut, Ph.D., and John Petros, MD at the forefront, this project leverages novel prodrug strategies and innovative formulations to amplify therapeutic efficacy while minimizing adverse side effects. This innovative leap promises to reshape the landscape of cancer treatment, offering patients a brighter, safer future.

OZ-Link, guided by the expertise of M.G. Finn, Ph.D., and Kasie Collins, Ph.D. from Georgia Tech, introduces a generalizable delivery platform that stands poised to transform drug delivery as we know it. By harnessing cutting-edge technologies and advanced formulation strategies, OZ-Link tackles the challenges associated with targeted drug delivery head-on. This groundbreaking platform holds immense potential, offering a lifeline to patients across various therapeutic areas.

Biolocity's unwavering commitment to nurturing these visionary projects is not without its fruits. Over the years, project teams have collectively raised over $125 million in follow-on funding from both public and private sectors. Their success stories are told through thriving startup companies, industry licenses, and products that now grace the market.

As we stand on the precipice of a new era in medical technology, Biolocity's 2023-2024 cohort serves as a testament to human ingenuity and determination. These projects are not just scientific endeavors; they are beacons of hope for millions around the world, promising a brighter, healthier future for us all. ‣ COURTNEY LAW

COMMERCIALIZATION ADVISORY BOARD

Advisory Board RAFAEL V. ANDINO Vice President, Engineering & Manufacturing Clearside Biomedical, Inc. ME 1988 (Georgia Tech) CALEB M. APPLETON Investor Bison Ventures BME 2015 MARIO BALL U.S. Director of Sales Strategy and Commercial Execution Boston Scientific – Cardiology Group BME 2007 SYLVIA BARTLEY, PH.D. Chief of Staff JSI KELLY BOLDEN, M.D., FACS Surgeon & 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 GAUTAM GOEL, PH.D. Chief Data Science Officer hC Bioscience, Inc. MS BioE 2006, Ph.D. BioE 2009 ELIZABETH HARRISON CEO MetaSystems Group, Inc. 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 Director, Virtual Health Tulsa Innovation Labs BME 2012, MSBME 2014 ROBERT F. KIRSCH, PH.D. Chair, Department of Biomedical Engineering Executive Director, Cleveland FES Center Case Western Reserve University XAVIER LEFEBVRE, PH.D. Partner Boston Life Sciences Advisors Ph.D. ChBE 1992 JASON LITTEN, M.D. Chief Medical Officer Chimeric Therapeutics M.D. 2002 (Emory) DEV MANDAVIA VP Strategy and Corporate Development OXOS Medical BME 2018 BRAD MILLER Chief Business Officer JISEKI Health NBB 2001 (Emory) 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 proximal tubule organoid is 30 days old and will survive at least another 60 days. Researchers say that keeping drop cultures viable for more than three months can allow them to closely observe a chronic condition, which could be useful for drug testing. Page 14.

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