Wallace H. Coulter Department - BME Fall Mailer 2018 by Coulter BME at Emory & Georgia Tech

From the Chair Founded in 1997, the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University grew rapidly, emerging as a leader in biomedical engineering research and education. We are excited to celebrate 20 years of innovation, inclusion, and impact. Since the establishment of our unique public-private university partnership, we have been consistently ranked as one of the nation’s top biomedical engineering programs. In world-class research and teaching facilities on two campuses, our bold scholars forge novel pathways to pioneer critical new engineering and biomedical knowledge needed to develop tomorrow’s clinical therapies and advanced technologies. Professor Scott Hollister recently created custom 3D-printed tracheal splints to save lives of babies with life-threatening airway obstructions. With FDA clearance for clinical trials, Professor Michael Davis is propelling his cell therapies and 3D-printed heart valve patch from laboratory to patients to treat cardiac disease. Professor Phil Santangelo has taken a giant leap in improving global health by preventing HIV and influenza transmission with an RNA-based gene therapy. In this booklet, we describe many additional exciting biomedical engineering discoveries that are already being translated to impactful solutions for challenging problems in medicine. We added eight new faculty members this year to accelerate discovery in our laboratories and classrooms and expanded our impact beyond our Georgia Tech and Emory campuses. Our faculty are consistently selected by federal agencies and our nation’s most prominent science and technology-focused foundations to investigate some of the nation’s most pressing healthcare needs.

The Coulter Department flourishes by embracing collaborations, entrepreneurial endeavors, and diverse thinking in a setting that is rich with resources on two campuses. A $51 million NIH CTSA grant accelerates research translations to improve patient outcomes. Our academic and industry-leading cell therapy development and manufacturing initiative has been expanded aggressively with an investment of $60 million and a dedicated new Good Manufacturing Practices (GMP) facility. In September, we learned that NIH designated us as a national point of care (POC) technology accelerator. Concurrently, we signed a collaborative agreement with Celltrion, a global biopharmaceutical company, to develop new therapies for atherosclerosis. We are developing the leaders of tomorrow in our laboratories and classrooms. Robert Mannino, who recently graduated with his Ph.D. in biomedical engineering, won two national business competitions and $200,000 in prize money during his last year of study to develop a smartphone app to non-invasively diagnose anemia. A Mayo Clinic sponsored senior design team took third place in NIBIB‘s national Design by Biomedical Undergraduate Teams (DEBUT) Challenge for their lumbar needle placement technology. Coulter Biomedical Engineering has launched ESTEEMED, an NIH STEM co-curricular program to nurture and cultivate a diverse pipeline of biomedical engineers. Our department, university, and industry partnerships are delivering real-world healthcare solutions to create a better tomorrow for all of us. Please join us in our celebration of 20 years of innovation, inclusion and impact. We welcome you to join our journey forward.

Sincerely, Susan Margulies, Ph.D. Wallace H. Coulter Chair, Coulter Department of Biomedical Engineering at Georgia Institute of Technology & Emory University Georgia Research Alliance Eminent Scholar in Injury Biomechanics Professor of Biomedical Engineering

BME at a Glance

No.

BME graduate program in the nation U.S. News & World Report, Spring 2018

1,203

263

U N D E R G R A D U AT E ENROLLMENT

254

B.S. DEGREES AWARDED, 2017-18

No.

BME undergraduate program in the nation U.S. News & World Report, Fall 2018

DEGREE PROGRAMS:

G R A D U AT E ENROLLMENT

PH.D. DEGREES AWARDED, 2017-18

Georgia Tech B.S. in BME Georgia Tech M.S. in BME Georgia Tech M.S. in Biomedical Innovation and Development Joint Georgia Tech & Emory University Ph.D. in BME Georgia Tech Interdisciplinary Ph.D. programs in: • Bioengineering • Bioinformatics • Computational Science • Machine Learning

$33M

• Robotics

T O TA L N E W R E S E A R C H A W A R D S , FY2018

Georgia Tech, Emory University, & Peking University Ph.D. in BME

LEADERSHIP: Susan Margulies The Wallace H. Coulter Chair

Essy Behravesh Director of Undergraduate Studies

Paul J. Benkeser Senior Associate Chair

Michael Davis

Associate Chair for Graduate Studies

Hanjoong Jo

Kyla Ross Director of Graduate Training

Ajit Yoganathan

Associate Chair for Emory

Associate Chair for Translational Research

Joe Le Doux

Cheng Zhu

Associate Chair for Undergraduate Learning and Experience

Executive Director for International Programs

3D Printed Devices Save Children’s Lives

hildren’s Healthcare of Atlanta has performed Georgia’s first-ever procedure to place 3D-printed tracheal splints in a pediatric patient. A crossfunctional team of Children’s surgeons used three custommade splints, which biomedical engineers at Georgia Tech helped create using an innovative and experimental 3D-printing technology, to assist the breathing of a 7-monthold patient battling life-threatening airway obstruction.

“We are so fortunate to work with a leading engineering school like Georgia Tech to find innovative, potentially life-saving treatment options for our patients,” said Donna Hyland, president and CEO, Children’s Healthcare of Atlanta. “This is a great example of how aligning Children’s clinical expertise with the missions of our research collaborators can improve patient outcomes. Research that can be translated into more effective care at the bedside is why our collaboration with Georgia Tech is so important for the future of pediatric care in Georgia.”

The patient who received the groundbreaking surgery is a 7-month-old boy battling both congenital heart disease and tracheo-bronchomalacia, a condition that causes severe life-threatening airway obstruction. During his six-month inpatient stay in the Pediatric Intensive Care Unit at Children’s, he experienced frequent episodes of airway collapse that could not be corrected by typical surgery protocols. The clinical team proposed surgically inserting an experimental 3D-printed tracheal splint, which is a novel device still in development, to open his airways and expand the trachea and bronchus. Scott Hollister, Ph.D., who holds the Patsy and Alan Dorris Endowed Chair in Pediatric Technology, a joint initiative supported by Georgia Tech and Children’s Healthcare of Atlanta, developed the process for creating the tracheal splint using 3D printing technology at University of Michigan C.S. Mott Children’s Hospital prior to joining Georgia Tech. The Children’s procedure was the 15th time a 3D-printed tracheal splint was placed in a pediatric patient. “The possibility of using 3D printing technology to save the life of a child is our motivation in the lab every day,” said Hollister, who is also the director of the Center for 3D Medical Fabrication at Georgia Tech and a professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University. “We’re determined to develop innovative solutions that meet the needs of Georgia’s most complex pediatric patients.” The splints were created using reconstructions of the patient’s airways from CT scans. Hollister and his team of biomedical engineers collaborated with the Global Center for Medical Innovation (GCMI) so that GCMI could create multiple versions of the splint, of varying sizes, to ensure the perfect fit was available for the surgical team to select and place around the patient’s airways during surgery. GCMI will also support the ongoing development and commercialization of the technology.

3D printed tracheal splints are shown around a model of a patient’s trachea.

Right: Research Scientist Sarah Jo Crotts and Biomedical Engineering Professor Scott Hollister are shown at the Global Center for Medical Innovation (GCMI).

In a complex 10-hour surgery, Children’s cross-functional team of surgeons successfully placed three 3D-printed splints around the patient’s trachea. The splints will eventually be absorbed into the body, allowing for expansion of the trachea and bronchus. The Children’s tracheal splint team included Steve Goudy, M.D., and April Landry, M.D., (ENT), pediatric otolaryngologists; Subhadra Shashidharan, M.D., pediatric cardiothoracic surgeon; and Kevin Maher, M.D., pediatric cardiologist. All three physicians are faculty members in the Emory School of Medicine. “It’s the close relationships we have with our research collaborators that make this kind of groundbreaking procedure possible,” said Dr. Goudy. “A large number of additional physicians, support staff and outside collaborators worked together on this innovative procedure.” The 3D-printed tracheal splint is a new device still under development, as safety and effectiveness have not yet been determined and is therefore not available for clinical use. The Children’s team sought emergency clearance from the FDA to move forward with the procedure under expanded access guidelines.

“The possibility of using 3D printing technology to save the life of a child is our motivation in the lab every day. We’re determined to develop innovative solutions that meet the needs of Georgia’s most complex pediatric patients.” Scott Hollister Director of the Center for 3D Medical Fabrication at Georgia Tech Professor, Coulter Department of Biomedical Engineering

Engineers Decode Conversations in Brain’s Motor Cortex

ow does your brain talk with your arm? The body doesn’t use English, or any other spoken language. Biomedical engineers are developing methods for decoding the conversation, by analyzing electrical patterns in the motor control areas of the brain. The new research is published online in the journal Nature Methods. In this study, the researchers leveraged advances from the field of “deep learning”-- powerful new artificial intelligence-based approaches that have revolutionized many technology industries in the last few years. The new computing approaches, which use artificial neural networks, let researchers uncover patterns in complex data sets that have been previously overlooked, says lead author Chethan Pandarinath, Ph.D. Pandarinath and colleagues developed an approach to allow their artificial neural networks to mimic the biological networks that make our everyday movements possible. In doing so, the researchers gained a much better understanding of what the biological networks were doing. Eventually, these techniques could help paralyzed people move their limbs, or improve the treatment of people with Parkinson’s, says Pandarinath, an assistant professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University. Pandarinath leads the Emory and Georgia Tech Systems Engineering Lab. For someone who has a spinal cord injury, the new technology could power “brain-machine interfaces” that discern the intent behind the brain’s signals and directly stimulate someone’s muscles.

“In the past, brain-machine interfaces have mostly worked by trying to decode very high-level commands, such as ‘I want to move my arm to the right, or left’,” Pandarinath says. “With these new innovations, we believe we’ll actually be able to decode subtle signals related to the control of muscles, and make brainmachine interfaces that behave much more like a person’s own limbs.”

Network behavior ‘emergent’ from individual neurons Previous research on how neurons control movement have revealed that it’s difficult to discern individual neurons’ roles, in a way that we might think of in a basic machine. Individual neurons’ behaviors don’t correspond to variables like arm speed, movement distance or angle. Rather, the rhythms of the entire network are more important than any individual neuron’s activity.

Pandarinath likens his team’s approach to ornithologists studying the flocking behavior of birds. To understand how the group holds together, one has to know how one bird responds to its neighbors, and to the flock’s movements as a whole. Flocking behavior is “emergent” from the interactions of the birds with each other, he says. Such emergent behaviors are challenging to characterize with standard methods, but are precisely the way artificial neural networks function.

Pandarinath

Pandarinath started investigating this approach, called LFADS (Latent Factor Analysis via Dynamical Systems), while working with electrical engineer Krishna Shenoy, PhD, and neurosurgeon Jaimie Henderson, MD, who co-direct the Neural Prosthetics Translational Lab at Stanford University. In the Nature Methods paper, the researchers analyzed data from both rhesus macaques and humans, who had electrodes implanted in the motor cortex. In some experiments, monkeys were trained to move their arms to follow an on-screen “maze,” and the researchers tested their ability to “decode” the monkeys’ arm movement trajectories based solely on the signals recorded from the implanted electrodes. Using their artificial neural network approach, the researchers were able to precisely uncover faint patterns that represented the brain rhythms in the motor cortex. They also observed similar patterns in human patients who were paralyzed – one because of motor neuron degeneration (amyotrophic lateral sclerosis), and another with spinal cord injury. In addition to the motor cortex, Pandarinath believes the new approach could be used to analyze the activity of networks in other brain regions involved in spatial navigation or decision making. Future plans for clinical applications include pairing the new technology with functional electrical stimulation of muscles for paralyzed patients, and also the refinement of deep brain stimulation technology in Parkinson’s disease. In addition, Pandarinath and colleagues have begun using these techniques to start to understand the activity of neurons at fundamentally different scales than were previously possible. This future work is supported by a recent grant from the National Science Foundation.

Gates Foundation Funds Mucosal Drug Delivery: Working Towards Preventing HIV and Influenza Transmission

hil Santangelo, associate professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, knows that preventing both HIV and flu infections are two tremendous challenges in the field of infectious disease. With support from the Bill and Melinda Gates Foundation and the NIH, the Santangelo lab is using RNA-based therapies to confront these challenges head on. His work is focused on the development of mRNA-based therapies, and the development and engineering of new molecular imaging technology for the interrogation of viral infections and immunodynamics. Throughout last year, the Santangelo lab has been working on a safe, RNAbased gene therapy for preventing HIV infections in women. In two large animal models, his research has demonstrated broadly neutralizing antibody production for over 28 days with a single administration, and protection of biopsies from HIV challenge—encouraging results in the area of HIV prevention.

Associate Professor Phil Santangelo and research scientist Chiara Zurla, a member of Santangelo’s lab.

Santangelo is noted as a “thought-leader” in both the areas of HIV imaging and the characterization of infections at the single cell level. Santangelo’s imaging of CD4+ cells in vivo has been noted by Francis Collins, the director of NIH, on his blog. Accomplishments by Phil Santangelo include: • •

A new assembly mechanism for respiratory syncytial virus particles was discovered. The first PET/CT contrast agent to image SIV and SHIV infected cells within live animals was demonstrated.

•

The first PET/CT contrast agent for imaging immune cells in macaques was demonstrated, and was used to validate the efficacy of a new treatment for HIV. The first RNA-based therapeutic for the prevention of RSV was demonstrated in rodents, with flu experiments underway. The first RNA-based therapeutic for the prevention of HIV was demonstrated in sheep and macaques.

His research has demonstrated that through the application of engineering principles to infectious diseases and other pathologies, significant impact can be achieved regarding both our fundamental understanding of pathogenesis, but also how these pathologies can be both prevented and treated.

Ultrasound Treatment Delivers Drug Directly to Brain

etting cancer drugs to permeate tumors can be tough, especially in the brain, but researchers have been using ultrasound to massage the drugs into malignancies that have taken root there. A new study details how the experimental method has overcome various barriers to treating cancers in the brain.

“The blood-brain barrier is a challenge in the treatment of brain malignancies,” said Costas Arvanitis, an assistant professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University. “Even when a drug reaches the brain’s circulation, abnormal blood vessels in and around tumors lead to nonuniform drug delivery with low concentrations in some areas of the tumor.” If a drug does make it through the distorted blood vessels, then dense tumorous tissue often blocks the drug’s path to the malignant cells. Arvanitis co-led the new study with Dr. Vasileios Askoxylakis at Massachusetts General Hospital to explore the effectiveness of ultrasound that is focused on affected brain areas to buzz the drugs through these barriers and into the cancer. Already, the method had proven effective enough in fighting tumors to make it to phase I clinical trials, but until now, it was not well observed how it actually worked.

Beaming tumors The team, which included researchers from the University of Edinburgh, and Brigham and Women’s Hospital, published its findings in the journal Proceedings of the National Academy of Sciences on August 27, 2018. The research was funded by the National Institutes of Health, the German Research Foundation, the Solidar-Immun Foundation, the Harvard Ludwig Cancer Center, and the National Foundation for Cancer Research.

“We established that we were able to get more of both drugs across blood vessel walls,” said Yutong Guo, a graduate student in Arvanitis’s lab and coauthor of the study. “The doxorubicin molecule is small, and it got the bigger boost, but altogether, the therapy distributed more of both drugs to more tumor tissue.” Also, the fluid that surrounds cells, interstitial fluid, which can serve as a conduit for drugs, was seen flowing more freely between cells of a tumor in high-resolution images taken following ultrasound treatment. The drugs appeared to make it through significant barriers to reach tumors. “Evidence of increased cellular transmembrane transport and uptake of doxorubicin by focused ultrasound was largely unknown until now,” Askoxylakis said.

Optimizing treatment The researchers quantified the changes in tissues and in cellular drug transport properties using mathematical modeling and used this to devise parameters for optimal drug delivery, which may prove useful in the design of new rounds of clinical trials. The study may also stimulate a broader discussion on how some cancer drugs should be administered, perhaps in some cases as a slow infusion rather than a quicker injection. The researchers would like to explore tuning the new method to optimize delivery of varying drugs or engineered immune cells to fight an array of tumors occurring in the brain.

The therapy is minimally invasive, focusing multiple beams of ultrasound energy onto a cancerous spot, where microbubbles, tiny lipid bubbles in the bloodstream that vibrate in response to ultrasound signals, can temporarily breach the bloodbrain barrier at the target site. That creates an opening for drugs to get through. The microbubbles are injected intravenously before ultrasound is applied.

Observing success The team studied the new method on mice with metastasized breast cancer cells in the brain. In lab experiments, the researchers observed improved delivery of two cancer therapies, the common chemotherapy drug doxorubicin, and the targeted drug T-DM1.

New Therapies for Childhood Heart Disease using Stem Cells and 3D Printing

ongenital heart disease (CHD) affects nearly nine in every 1,000 babies born. In fact, it’s the world’s most common birth defect. Researchers and clinicians today have begun applying stem cell therapies and 3D tissue printing to pediatric heart defects. Michael Davis, director of Children’s Healthcare of Atlanta’s Heart Research and Outcomes Center (HeRO) under the Georgia Tech and Emory University’s Department of Biomedical Engineering, is busy pushing the boundaries on innovative stem cell research with clinical trials, predictive medicine models and 3D printing. Davis’ lab focuses on pediatric heart failure and general defects. Mostly, he’s dealing with patients who have congenital issues, including hypoplastic left heart syndrome (HLHS) and left ventricular cardiomyopathy. Being local to Atlanta, Children’s Healthcare of Atlanta offers Davis and his team of researchers access to a large volume of young cardiac patients who need the help of his new and developing therapies. “With pediatrics, clinicians are very open to collaborating and trying new procedures and therapies,” said Davis. “In the pediatric world, there are fewer options for these kids, and the parents and clinicians are hungry for new therapies to try.”

Designing Targeted Stem Cell Therapies A few years ago, Davis noticed that during bypass surgery, small amounts of tissue were being removed to run the bypass tubing into the heart, and surgeons were throwing it away after removal. As the new director of HeRO at the time, he asked and was granted permission to use the tissue in his research lab for stem cell studies. Davis began extracting and quantifying the stem cells, eventually finding that the young cells had more reparative qualities, and when injected into damaged tissue, released healing proteins. Davis’ first clinical trial with the stem cells (Autologous Cardiac Stem Cell Injection in Patients with Hypoplastic Left Heart Syndrome (ACT-HLHS) Trial) is happening in the next few months and has already been cleared by the FDA. Clinicians will inject the stem cells into the hearts of babies with CHD to boost the function of the heart. “For a baby with HLHS, we are not going to re-grow the left ventricle, but rather try to strengthen and prevent deterioration of

the existing right ventricle,” said Davis. “It sets the baby up for a successful repair surgery down the road.” In his lab, Davis observes the cells and gathers quantitative data on their behavior. The research is conducted for cord blood, bone marrow and cardiac stem cells, which is where Davis’ work is revolutionizing his field. Davis and Manu Platt, diversity director of STC on Emergent Behaviors of Integrated Cellular Systems (EBICS) at Georgia Tech, have written a grant in the hopes of combining all the cellular data from patients in three different clinical trials to create a large data repository of cell signals. By studying the signals, otherwise known as protein secretions of the cell, Davis and Platt can determine how effective certain cells are in treating diseases. “These cells could be acting a number of ways, and we want to collect all the information we can, including their genome and what they release,” said Davis. “We essentially want to make equations to determine how cells will respond. We want to put the data together to create a treatment prediction.” With this information, they will be able to build a mathematical model that identifies the cell genome in order to predict what the cell will do in the clinic. The goal is to identify the best characteristics of these cells and determine which diseases they can target to begin the reparative process. “If we can study the cells and isolate their response, we will be able to provide personalized approaches to stem cell therapy – that’s really what the field is currently lacking,” said Davis. “A patient could come in, and we could sequence their cells and know immediately what cells to inject for the best outcome. Different cells are going to have differing effects on each individual.”

Innovations in 3D Printing The 3D printing in Davis’ lab is used to create valves, leaflets and patches. Aline Nachlas, a fourth-year Ph.D. biomedical engineering candidate, has earned a fellowship for tissue engineering, with the goal of creating valve cells. She has also found a material that will support the printing of these cells. The valves are made using skin cells from the patient, so essentially, they are growing their own cells, minimizing the risk of organ rejection. And ideally, the valve will continue to grow with the patient, never needing to be replaced.

“We hope these cells will be able to print valves, or at least the leaflets that make up valves,” said Davis. “Currently, children are undergoing animal valve replacements, which are sometimes too big, and they don’t grow with the child. This means more surgeries down the road to replace the valve, as well as high doses of immunosuppressants. We want to create a living valve that grows with the child.” Davis’ lab is also working on a printable patch that contains stem cells. The patch functions to keep all the stem cells in one place, so the cells can repair the surrounding tissue. Davis’ student is hoping to print the patch scaffold with a decellularized pig material matrix. “Very few people are trying to heal with 3D printed patches,” said Davis. “My lab is on the forefront of that research. We are trying to make a positive contribution in a sensible way.” Next up for Davis is a summer trip to Galway, an international biotechnology hub, where he will teach tissue engineering to Georgia Tech biomedical engineering students. In the next five to 10 years, he hopes to be more focused on 3D printing and really pushing the envelope on printing small tissues. Davis wants to bring more regenerative therapies to the greatest number of children possible. “My research may not always move at the speed I want, so I try to remember there is a bigger picture,” said Davis. “We are already helping many kids with CHD become healthier and stronger. But, I am always asking myself ‘what can we do better?’” • GEORGIA PARMELEE To learn more about Michael Davis’ research and lab, visit https://www.facebook.com/Childrensheartresearch/.

Photos from the top: a 3D printed valve; Michael Davis in his lab at Emory University; a 3D printed stem cell patch.

Turning on Cancer-Killing Immune Cells

remote command could one day send immune cells on a rampage against a malignant tumor. The ability to mobilize, from outside the body, targeted cancer immunotherapy inside the body has taken a step closer to becoming reality. Biomedical engineers at the Georgia Tech have installed a heatsensitive switch into T-cells that can activate the T-cells when heat turns the switch on. The method, tested in mice and published in a new study, is locally targeted and could someday help turn immunotherapy into a precision instrument in the fight against cancer. Immunotherapy has made headlines with startling high-profile successes like saving former U.S. President Jimmy Carter from brain cancer. But the treatment, which activates the body’s own immune system against cancer and other diseases, has also, unfortunately, proved to be hit-or-miss. “In patients where radiation and traditional chemotherapies have failed, this is where T-cell therapies have shined, but the therapy is still new,” said principal investigator Gabe Kwong, assistant professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University. “This study is a step toward making it even more effective.”

Cancer is notoriously wily, and when T-cells crawl into a tumor, the tumor tends to switch off the T-cells’ cancer-killing abilities. Researchers have been working to switch them back on.

Laser, gold, and T-cells Kwong’s remote control has done this in the lab, while also boosting T-cell activity. In the study, Kwong’s team successfully put their remote-control method through initial tests in mice with implanted tumors (socalled tumor phantoms, specially designed for certain experiments). The remote works via three basic components. First, the researchers modified T-cells, a type of white blood cell, to include a genetic switch that, when switched on, increased the cells’ expression of specific proteins by more than 200 times. That ability could be used to guide T-cells’ cancer-fighting activities. The T-cells, with the switch off, were introduced into the tumor phantom which was placed into the mice. The tumor phantom also included gold nanorods, just dozens of atoms in size. The researchers shone pulses of a gentle laser in the near-infrared (NIR) range from outside the mouse’s body onto the spot where the tumor was located. The nanorods receiving the light waves turned them into useful, localized mild heat, allowing the researchers to precisely warm the tumor. The elevated heat turned on the T-cells’ engineered switch.

Hyper-activated T-cells This study honed the method and confirmed that its components worked in living animals. The researchers published their results in the current edition of

the journal ACS Synthetic Biology. The study’s first author was graduate research assistant Ian Miller. “In upcoming experiments, we are implementing this approach to treat aggressive tumors and establish cancer-fighting effectiveness,” said Kwong.

Better immunotherapy “Right now, we’re adept at harvesting a patient’s own T-cells, modifying to target cancer, growing them outside the body until there are hundreds of millions of them,” Kwong said. “But as soon as we inject them back into a patient, we lose control over the T-cells’ activity inside the body.” The on-switch changes that.

T-cell toxicities Having an off-switch is also important. If T-cells were engineered to be always-on and hyper-activated, as they moved through the body, they could damage healthy tissue. “There would be off-target toxicities, so you really want to pinpoint their activation,” Kwong said. “Our long-term goal for them is to activate site-specifically, so T-cells can overcome immunosuppression by the tumor and become better killers there.” When the heat remote is turned off, so are Kwong’s engineered T-cells, because customary body temperatures are not high enough to activate their switch.

Kwong’s team found that the switch worked in a range of 40 to 42 degrees Celsius (104 - 107.6 F), high enough to not react to the majority of high fevers and low enough to not damage healthy tissue nor the engineered T-cells. “When the local temperature is raised to 45 degrees (113 F), some cells in our body don’t like it,” Kwong said. “But if heating is precisely controlled in a 40 to 42 degrees window with short pulses of the NIR light, then it turns on the T-cells’ switch, and body cells are still very comfortable.”

Immuno-goals and dreams The researchers want to combine the switch with some additional cancer-fighting weapons they envision engineering into T-cells.

Heat-shock switch

For example, secreted molecules called cytokines can boost immune cells’ ability to kill cancer, but cytokines, unfortunately, can also be toxic. “Our long-term goal is to engineer T-cells to make and release powerful immune system stimulants like cytokines on command locally and sparingly,” Kwong said.

The switch is a natural safety mechanism in human cells that has evolved to protect against heat shock and turns on when tissue temperatures rise above the body’s normal operating range, which centers on 37 degrees Celsius (98.6 F). But the researchers refitted T-cells with the switch to make it turn on other functions, and it could be used to hyper-activate the cells.

In other studies, gently heated gold nanorods have been shown to kill tumors or hinder metastasis. But T-cell treatments could be even more thorough and, in addition, hopefully, one day give patients treated with them a long-lasting memory immune response to any recurrence of their cancer.

Left: Assistant professor Gabe Kwong (r.) and graduate research assistant Ian Miller (l.) in Kwong’s lab at Georgia Tech. T-cells are preserved in the lab in liquid nitrogen. Above: Pulses from a near-infrared laser hit gold nanorods, which warm up T-cells in in vitro tests, successfully activating a genetic switch implanted in the T-cells.

Industry Partnership Accelerates Atherosclerosis Therapies to Market

elltrion signed an “incubation” agreement with Emory University to jointly research and develop new drug candidates for atherosclerosis. An incubation agreement is an open innovation arrangement in which a firm provides its resources and business capabilities, such as research facilities, workforce and operations consulting, to an external research institute. The arrangement aims to ensure the autonomy of the research while obtaining preferential rights to discuss commercializing the research output.

Under the agreement, Celltrion will share its accumulated biologics development expertise with the Emory University School of Medicine and the Wallace H. Coulter Department of Biomedical Engineering at Emory University and Georgia Tech, and provide research costs and manufacturing materials of new drug candidates for atherosclerosis. Celltrion will have a preferential right to acquire a license for inventions resulting from the agreement. Atherosclerosis is a vascular disease, in which the blood vessels are narrowed or clogged

due to plaque made up of fat, cholesterol, immune cells and vascular wall cells in the blood vessel. This results in ischemic heart diseases, such as myocardial infarction and angina, as well as stroke or peripheral arterial disease. Ischemic heart disease and stroke are the world’s leading causes of death. Statins that lower cholesterol and lipid levels in blood are widely used to alleviate the onset and progression of atherosclerosis. Despite the success of lipid lowering drugs, atherosclerotic diseases continue to be a major cause of death worldwide. This highlights the need to develop new drugs that can complement the lipid lowering drugs by targeting new mechanisms of action to prevent and reduce the risk of atherosclerotic diseases, Celltrion said. “We are delighted to cooperate with the internationally renowned research team at Emory University led by Dr. Hanjoong Jo, John and Jan Portman, Endowed Professor and associate chair in the Wallace H. Coulter Department of Biomedical Engineering and the Division of Cardiology, who is a leader in the area of mechanically regulated genes in atherosclerosis research,” said Celltrion.

Professor Hanjoong Jo, second from right, talking with his lab members at Emory University.

Andrés García, Regents’ Professor, executive director of the Petit Institute for Bioengineering and Bioscience and BME program faculty member, with Jessica Weaver, a Georgia Tech postdoctoral researcher, discuss pancreatic islet cells being studied in their laboratory. Pictured below: W. Robert Taylor, MD, PhD, Professor of Medicine and Biomedical Engineering in the Coulter Department, is the principal investigator contact for CTSA.

$51 Million NIH Grant Accelerates Research Translation to Improve Patient Outcomes This alliance is celebrating 10 years of research advancement by expanding across the state through a five-year, $51 million Clinical and Translational Science Award (CTSA) from the National Institutes of Health (NIH). The Emory University-led Georgia CTSA will focus on transforming the quality and value of clinical research and translating research results into better outcomes for patients. The Georgia CTSA unites the strengths of its academic partners: Emory University, Morehouse School of Medicine, the Georgia Institute of Technology, and the University of Georgia. Emory is a national leader in health care and biomedical research as well as an outstanding leader in clinical and translational research training and education. Morehouse School of Medicine is a nationally recognized historically black institution that brings ethnic diversity to biomedical research, addresses health disparities through successful community engagement research, and serves as a pipeline for training minority researchers. Georgia Tech is a national leader in biomedical engineering, bioinformatics and the application of innovative systems engineering to health care solutions. The University of Georgia has a proven track record in outstanding basic and translational research and, as the state’s land grant institution, offers a robust statewide network that enhances community outreach, service and research.

GMP Facility Launched in $60M Cell Therapy Development and Manufacturing Initiative

he vision of making affordable, high-quality cell-based therapies available to hundreds of thousands of patients worldwide moved closer to reality with the dedication of a new cell manufacturing research facility at Georgia Tech aimed at changing the way we think about medical therapies. The new Good Manufacturing Practice (GMP) like ISO 8 and ISO 7 compliant facility is part of the existing Marcus Center for Therapeutic Cell Characterization and Manufacturing (MC3M). The center was established in 2016 and made possible by a $15.75 million gift from philanthropist Bernie Marcus, with a $7.25 million investment from Georgia Tech and $1 million from the Georgia Research Alliance. Another $21 million will be provided by NIH along with an additional $1 million from the state of Georgia. Marcus gave a second gift of $13 million for cell therapy clinical trials at Emory. MC3M is already helping researchers from Georgia Tech and partner organizations develop ways to provide therapeutic living cells of consistent quality in quantities large enough to meet the growing demands for the cutting-edge treatments. The center and this new facility also provide the infrastructural foundation for the Georgia Tech-led National Science Foundation Engineering Research Center for Cell Manufacturing Technologies (CMaT). The Marcus Foundation’s gift along with the NSF’s expected funding over ten years in CMaT, together with potential private-sector contributions and the state of Georgia’s investment in infrastructure related bio manufacturing, could result in a combined statewide investment of more than $70 million in cell manufacturing. Beyond developing technologies to help make these life-saving cell therapies broadly available and affordable, the initiative will also help train the specialized workforce needed to manufacture these therapies at large scale. “This initiative has the potential to change the way we think about medical treatments, to change the way we think about medicine, and the way we approach cures for different diseases,” said Georgia Tech President G.P. “Bud” Peterson, who opened the dedication event. “Here, we will develop the tools and technologies to produce these cells at lower cost, more rapidly and for more people.”

MC3M is already supporting 23 research projects aimed at all components of the challenge, from understanding cell quality and developing scalable processes, to chip-based disease models for safety and efficacy testing and new models for supply-chain optimization and logistics. The center collaborates with several other institutions, supporting the work of 29 faculty members, and helping train 27 students and fellows for the emerging cell manufacturing industry. The new facility dedicated on June 6 is a unique “sandbox” for collaboration among engineers, clinicians, and industry to develop and validate new scalable manufacturing processes for cell therapies under GMP conditions necessary to eventually obtain regulatory approvals. It will serve as the translational arm of the Marcus Center and CMaT to help researchers throughout the state of Georgia translate emerging cell therapies to clinical practice. This facility – designed to enable real time quality monitoring and control of cell products during manufacturing – is a one-of-a-kind space that will be instrumental in bringing affordable cell therapies to patients faster. The new cell-based therapies being approved for use in humans can have dramatic impact. But the therapies are costly, as much as a $500,000 per patient. The MC3M will help develop new technologies and processes to make these treatments consistent in quality and available to the average person.

“The center is about providing access for patients and enabling patients to benefit from these incredible therapies that could change their lives. We need to scale these therapies up to treat hundreds of thousands of patients. This is the vision of Mr. Marcus – to make this available to everyone regardless of their socio-economic status.” Krishnendu Roy “The center is about providing access for patients and enabling patients to benefit from these incredible therapies that could change their lives,” said Krishnendu Roy, who directs both MC3M and CMaT. “We need to scale these therapies up to treat hundreds of thousands of patients. This is the vision of Mr. Marcus — to make this available to everyone regardless of their socio-economic status.” Marcus, who recalled working as a pharmacist before co-founding home improvement retailer The Home Depot, noted that common drugs such as aspirin are chemically consistent around the world, regardless of where they are sold. The consistency of living cell therapies can’t be similarly counted on because their properties may depend on the specific skills and facilities of the research center producing them. “Patients receiving these cells need to know that they are getting the right things,” Marcus said. “This is a very practical question for which we have no answer now.” Beyond consistency, the cells also need to be affordable, he said. The new cell manufacturing facility will connect cell-based therapies being developed in research facilities with the appropriate

tools and technologies that ensure consistency in manufacturing and product quality while enabling scalability. “There is a gap right now between what we do in the research lab and what we need to do to get these therapies to a hundred thousand or even millions of patients,” Roy noted. Beyond developing quality control and analytical techniques to ensure consistency, the center will also develop novel feedback-controlled automation systems to lower the cost, Roy said. Peterson noted the potential economic impact of building a cell manufacturing industry in Georgia. “Working with our partner universities, the Technical College System of Georgia and the private sector, we will be able to attract new industries, create new jobs and help build the economy of the state of Georgia.” The NSF ERC could provide up to $40 million over ten years, and attract private and local investment that could boost that amount much higher. “We have incredible momentum,” Roy said. “We are bonded together by a single goal: getting these therapies to many patients at a lower cost to really help them.”

Professor Krishnendu Roy, director of the NSF Engineering Research Center (ERC) for Cell Manufacturing Technologies (CMaT) at Georgia Tech, receives a three-year $1.8 million grant in advanced biomanufacturing from the U.S. Food and Drug Administration. Georgia Tech is one of only five award recipients from the FDA made through a national proposal call. The other awardees were MIT, Harvard University, Carnegie-Mellon University, and Rutgers University. As the principle investigator, Roy is being tasked by the FDA to build a scalable manufacturing system for cord-tissue derived cells that identify critical quality attributes, incorporates real-time sensing, and develops automation. “Advanced manufacturing technologies, such as continuous manufacturing, hold great promise for improvements in the reliability, flexibility and cost effectiveness of manufacturing for biological products. These platforms may be critical to unlocking the full potential of very novel technologies like cell and gene therapies, and new vaccines. Grants like these help encourage the establishment of high tech manufacturing platforms in the U.S., potentially providing an opportunity to bring more manufacturing back to American soil,” said FDA Commissioner Scott Gottlieb, M.D.

New $7M NIH Point of Care Technology Innovation Center

new NIH-funded research center at Emory, Georgia Tech, and Children’s Healthcare of Atlanta will assist inventors across the United States in developing and translating microelectronicsbased point-of-care (POC) technologies for patient care. Point-of-care technologies are medical diagnostic tests performed outside the laboratory in close proximity to where a patient is receiving care. This allows health care providers to make clinical decisions more rapidly, conveniently and efficiently.

has enabled rapid and timely clinical evaluation in the physician’s office, ambulances, homes, in the field, or in hospitals, and has the potential to significantly impact health care delivery,” says Martin. “In cardiology, pulmonology/critical care and hematology, POC testing can play an especially significant role, as the heart and lungs are among the most vital organs, and real-time diagnosis and rapid management during critical illnesses is key to avoiding progression to the difficult challenges of systemic and critical illness.”

The Atlanta Center for Microsystems Engineered POC Technologies (ACME POCT) will be funded by a $7 million, five-year grant from the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health. The ACME POCT will be part of the national NIH Pointof-Care Technologies Research Network. The Atlanta center will assist and enable inventors of POC technologies for cardiac, pulmonary, hematologic, and sleep applications to translate them to improve patient care.

One focus of the new research center will be microsystems-engineered technologies, a promising new class of microchip-enabled POC devices ranging from microelectromechanical systems (MEMS)-based sensors, to microfluidics, to smartphone-based systems. Examples include CardioMEMs’ heart failure sensor and Medtronic’s Carelink system for cardiac patients. “The ACME POCT will be able to leverage the extensive open-access micro- and nanofabrication facilities at Georgia Tech’s Institute for Electronics and Nanotechnology to refine microchip-based point-of-care technologies,” states Brand.

Principal investigators for the ACME POCT are Oliver Brand, Ph.D., a microsystems engineer, professor at Georgia Tech’s School of Electrical and Computer Engineering and executive director of Georgia Tech’s Institute for Electronics and Nanotechnology (IEN); Wilbur Lam, M.D., Ph.D., associate professor of pediatrics at Emory School of Medicine and the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, and a clinical hematologist at Children’s Healthcare of Atlanta; and Greg Martin, M.D., M.Sc., professor of medicine at Emory School of Medicine, clinical pulmonologist and intensivist, and head of the clinical research network in the NIH-funded Georgia Clinical and Translational Science Alliance (Georgia CTSA). “In the last several decades, the introduction of POC diagnostic capabilities

“The field of microfluidics is also finding increasing applications for bloodbased diagnostics, but their clinical use and success has been less than expected, due primarily to clinician concerns about accuracy, usability, cost and reimbursement, as well as regulatory hurdles,” notes Lam. “We think the timing is ripe for a POC center dedicated to developing microsystem-engineered POC technologies that address these barriers to clinical adoption at an early stage, before the technology goes to market.” The ACME POCT will assist inventors of microsystems-based POC technologies to define their specific clinical needs, conduct clinical validation, and refine their technology, directly addressing barriers with the objective of accelerating the path to clinical adoption.

Collaborating for Kids Faculty researchers in the Coulter Department of Biomedical Engineering are partnering with the Aflac Cancer and Blood Disorders Center at Children’s Healthcare of Atlanta, one of the nation’s leading pediatric health care systems, to develop better diagnostic tools and treatment technologies for a range of diseases that plague our nation’s youngest patients. Sickle cell disease, for example, is a blood disorder that can have profound effects on the brain. Children with this disease have a high risk of stroke and cognitive deficits, which may be caused by poor blood flow and oxygen delivery to the brain. Assistant Professor Erin Buckley is addressing an urgent clinical need to better measure microvascular blood flow in the brain and improve detection of stroke risk, treatment monitoring, and prediction of neurocognitive outcome. Buckley’s lab is investigating the feasibility of a new, low-cost, non-invasive optical technology, known as diffuse correlation spectroscopy (DCS), that can quantify blood flow in the brain. The goal is to identify unique applications for noninvasive optical technology. Children’s sees the largest cohort of sickle cell kids in the country, so there is no better place for this research.

$3 Million NIH Study Focuses on Sickle Cell Disease with Microfluidic and Computational Modeling The National Institutes of Health has awarded a four-year, $3 million grant to a research team at Emory and Georgia Tech that will use new technologies to improve the effectiveness of blood transfusions in patients with sickle cell disease. The research will take place in the labs of Wilbur Lam, M.D., Ph.D., and Melissa Kemp, Ph.D., both associate professors in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University and researchers in the Petit Institute for Bioengineering and Bioscience, and at the University of Minnesota lab of David Wood, Ph.D. Lam is also part of the Aflac Cancer and Blood Disorders Center of Children’s Healthcare of Atlanta. The NIH-funded project is entitled “Redefining clinical viscosity in sickle cell disease by leveraging microfluidic technologies.” Sickle cell disease is a life-threatening genetic blood disorder in which red blood cells become physically altered and misshapen. Viscosity, or resistance to flow, is a complex biophysical property of blood that changes in various parts of the circulation in the body and is rendered even more complex by sickle cell disease. “While blood viscosity in sickle cell disease is poorly understood,” explains Lam, “it remains important clinically, because physicians are instructed to use blood transfusions judiciously to avoid ‘hyperviscosity,’

“The infrastructure of the Coulter department has been phenomenal and has been key to helping me get this project off the ground,” said Buckley. “As a non-MD working with clinical patients, I rely on clinicians and clinical research coordinators for access to patients. The center is remarkably collaborative.” Assistant Professor Erik Dreaden wants to make immunotherapies for cancer more potent and specific by developing polymer-protein hybrid therapeutics that can be activated in response to various stimuli. He aims to use light to activate synthetic biomolecules which act as immunotherapies that can precisely dose patient tumors with therapeutic drugs in a more patient-personalized fashion. “Opportunities for collaborative, cross-cutting research at Aflac are near endless,” said Dreaden. “It’s rare to find medical centers with such strong institutional commitment to both patient care and cutting-edge research.”

but are also hampered by clinical transfusion guidelines that are not scientifically sound or evidence-based.” The researchers propose to use new microfluidic and computational modeling techniques to model the different blood vessels and to more precisely define what “viscosity” means in different parts of the circulation within a sickle cell disease patient. They also will study how viscosity changes in the context of blood transfusions, which will lead to more patient-specific transfusion guidelines. “We are grateful for this funding, and confident that the grant will allow us to make a significant contribution to redefining and improving guidelines for blood transfusions in sickle cell disease,” says Kemp. “This could make a significant difference in the quality of life and longterm health of these patients.”

hematology and oncology, and clinical medicine. His interdisciplinary laboratory, comprising clinicians, engineers, and biologists, is dedicated to applying and developing micro/nanotechnologies to study, diagnose, and treat blood disorders, cancer, and childhood diseases. With seven active Aflac-affiliated research projects, in addition to practicing medicine at Children’s, Lam routinely balances the demanding tasks of active researcher and practicing physician every day. His range of projects also involve students as co-inventors. One project created an inexpensive blood test that provides a visual result that correlates with the degree of anemia – this project launched a startup company called Sanguina. A former biomedical engineering undergraduate student from the Lam lab, Erika Tyburski, is now the CEO of this company, and Robert Mannino, Ph.D., a former biomedical engineering doctoral student, is the chief technology officer.

Within the Coulter Department, Associate Professor Wilbur Lam, who is also an M.D., operates one of the more robust research laboratories working with the Aflac Cancer and Blood Disorders Center. Lam’s research involves integrating microtechnology, experimental

Developing Better Cancer Diagnostics and Treatment

n 2017, Winship Cancer Institute of Emory University was made a National Cancer Institute-Designated Comprehensive Cancer Center in recognition of its research in discovering better approaches to cancer prevention, early detection, and cancer therapeutics as a means of lessening the burden of cancer on Georgians. A number of Winship scientists in the Coulter Department of Biomedical Engineering (BME) engage in cancer research projects that are fully aligned with Winship’s mission. These investigators take problem-solving approaches to a myriad of challenges in developing better cancer diagnostics and treatment.

One challenge they are tackling is that combination, or “cocktail,” chemotherapies often ignore ratio-dependent drug interactions that can either amplify or dampen cancer cell killing when local drug concentrations fluctuate following administration. The Precision Combination Nanomedicines project from the lab of Erik C. Dreaden, Ph.D., focuses on this problem by re-engineering cocktail chemotherapies for the 21st century. Dreaden’s lab approaches the problem of drug variability within the body by administering a fixed ratio of combination chemotherapy via an engineered nanoscale drug carrier which maintains optimal dosing ratios both in circulation and following cancer-targeted intracellular delivery. Working with Winship collaborators Douglas Graham, M.D., Ph.D. and Deborah DeRyckere, Ph.D., the lab employs high-throughput screening methods to identify unusually potent (synergistic) drug combinations and then engineers polymer and lipid drug carriers that specifically deliver these cocktails to malignant cells more safely and effectively than conventional means. “Methods used to deliver cocktail chemotherapies have remained essentially unchanged for more than fifty years. Using our approach, we can custom-tailor drug combinations for maximum killing of a specific cancer cell type. In essence, we’re squeezing as much cell killing as possible out of each drug molecule that we inject,” says Dreaden. Jaydev P. Desai, Ph.D., BME Distinguished Faculty Fellow and director of the Georgia Center for Medical Robotics, is developing minimally invasive neurosurgical robotic technology to more effectively remove deep-seated brain tumor. His project,

Minimally Invasive Neurosurgical Intracranial Robot (MINIR-II), is working on the development of an intracranial robot that is 3D-printed and which combines flexible robotic technology with magnetic resonance imaging (MRI) modality to achieve more precise, less invasive, and more complete removal of brain tumor. “MINIR-II has the potential to revolutionize the field of robotic neurosurgery by 3D printing a patient-specific robot that enables the physician to operate out of the line-of-sight and facilitate complete tumor removal,” says Desai. Desai’s lab is also investigating the physical properties of breast tissue, such as elasticity and electrical conductivity, as they change with the progression of the disease and act as biomarkers. Using microelectromechanical systems (MEMS), Desai says the project has the potential to diagnose cancer at an early stage by measuring the subtle changes and thereby facilitate cancer diagnosis from the onset through disease progression. The ability of tumor cells to invade surrounding tissue and spread to distant sites in the body tumors is a hallmark of cancer. The Integrative Systems Biology Lab, directed by BME faculty member Denis Tsygankov, Ph.D., is working at understanding the role of tumor microenvironment in the efficiency of cancer cell invasion. The goal of this project is to integrate novel computational and experimental approaches that enable systems-level understanding of how the structural properties of tumor environment control cell motility and the propensity for metastasis. “In most invasive solid tumors, histopathological samples show a variety of migration patterns, suggesting that tumor cells can employ different modes of invasion depending on the local microenvironment. Thus, the mechanistic dissection of the regimes of single-cell, streaming, and collective migration will be critical for understanding the metastatic progression and, ultimately, for identifying therapeutic targets for reducing tumor cell malignancy,” says Tsygankov.

The bioengineering/ hematology laboratory of Wilbur Lam, M.D., Ph.D. is developing an assay that enables testing of multiple chemotherapy drugs at every potential dose from a single blood or bone marrow sample for leukemia patients. This will allow better testing of existing chemotherapy “cocktails,” as well as testing of experimental therapeutics with the goal of improved personalization of the optimal chemotherapy regimen for adult and pediatric leukemia patients. “My bioengineering lab is applying state-of-theart microfluidic principles to create a test that can expose a single leukemia patient blood or bone marrow sample to different combinations of drugs – standard chemotherapy as well as newer, more experimental agents – that span all the relevant possible doses for each drug. This technology will be a much more efficient way to test how well therapies work on the patient’s cells before we actually give them to the patient and will ultimately help personalize their therapy,” says Lam.

Research Highlights

Comparison Shows Value of DNA Barcoding in Selecting Nanoparticles

al suspect, according to a new study from the lab of Cassie Mitchell, assistant professor in the Coulter Department.

The first direct comparison of in vitro and in vivo screening techniques for identifying nanoparticles that may be used to transport therapeutic molecules into cells shows that testing in lab dishes is not much help in predicting which nanoparticles will successfully enter the cells of living animals.

Though the bad amyloid-beta protein does appear to be an accomplice in the disease, the study has pointed to a seemingly more likely red-handed offender, another protein-gone-bad called phosphorylated tau (p-tau). A data analysis of multiple studies done on mice turned up signs that multiple biochemical actors work together in Alzheimer’s to tear down neurons, the cells that the brain uses to do its work.

“DNA barcoding has the potential to advance the science of selecting nanoparticles for delivering gene therapies,” said James Dahlman, an assistant professor in the Coulter Department and the study’s principal investigator. “Using this technique, companies and academic labs could pick out promising nanoparticles much more efficiently. That could accelerate the rate at which nanoparticle-based therapies move into the clinic, while reducing the amount of animal testing required.”

Suspicions Shift on Alzheimer’s It may be time to refocus Alzheimer’s research, as a new study strongly points to a biochemical culprit traditionally less pursued. Heaps of plaque formed from amyloid-beta that accumulate in afflicted brains are what stick out under the microscope in tissue samples from Alzheimer’s sufferers, and that eye-catching junk [amyloid-beta] has long seemed an obvious culprit in the disease. But data analysis of the cumulative evidence doesn’t support giving so much attention to that usu-

Mitchell said the data pointed to a pecking order of culpability. “The most important one would be the level of phosphorylated tau present. It had the strongest connection with cognitive decline,” Mitchell said. “The correlation with amyloid plaque was there but very weak; not nearly as strong as the correlation between p-tau and cognitive decline.” Mitchell, a biomedical informaticist, and first author Colin Huber statistically analyzed data gleaned from 51 existing lab studies in mice genetically augmented with a human form of Alzheimer’s.

Shedding Light on Movement Disorders When you respond to something automatically, without thinking, it’s called a “knee-jerk reaction.” It’s an old idiom based on what happens when the doctor uses his little hammer to strike your patellar tendon, just below the knee. Your knee jerks suddenly. That’s called a patellar reflex, and it’s caused by the muscle spindles in your quadriceps.

Pictured left to right: James Dahlman, Cassie Mitchell, Lena Ting, Kyle Blum, Shu Jia

New research by the Lena Ting lab, professor in the Coulter Department, may alter long-established views of muscle spindles, how they work, and how they affect people with neurological challenges and other movement issues. “The prevailing hypotheses about muscle spindles have been in place a long time — some of the research that has relied on these hypotheses may need to be reexamined in light of our study,” says Kyle Blum, a graduate student in Ting’s lab and lead author of the paper, “Force encoding in muscle spindles during stretch of passive muscle.” In general, the idea established over the past 50 years or so, according to Ting, is that muscle spindles fire in response to, or encode, the length and velocity of the muscle. “But we found that they fire in response to muscle force instead,” Ting says. “Time will tell, but I think this could ultimately be groundbreaking in how we understand movements and their disorders.”

Collaborating on Genome Imaging Shu Jia, assistant professor in the Coulter Department, is part of a team of researchers from three different institutions utilizing a National Science Foundation (NSF) grant to focus on human cardiac opto-epigenetics. Jia and his collaborators from George Washington University and Massachusetts General Hospital are recipients of a $2

million, four-year award from the NSF’s Emerging Frontiers in Research and Innovation (EFRI), for Chromatin and Epigenetic Engineering. The research team will develop a new framework and technology for linking epigenetic modulation to phenotype (epigenetics is the study of the biological mechanisms that switch genes on and off). The team is proposing development of new integrated imaging system for super-resolution imaging. “Documenting the sequence of events triggered by the epigenetic master-regulators of cell function has a broader impact for the fundamental understanding of biological function,” Jia says, “No such technology has been developed to date to link genome re-arrangement to phenotypic signatures in live cells upon an opto-epigenetic trigger.” The team expects its approach to provide a powerful way to probe chromatin-mediated control of transcription in real time, and generate fundamentally new information currently not available through chromatin mapping. The Jia lab has made its reputation working on super-resolution optical microscopy, developing and applying advanced biophotonic tools to study complex, dynamic biological systems at the nanometer scale. The team’s research aims to invent a host of methods that enable the extraction of structural, molecular and functional information from intact tissues and organisms.

The Coulter Department welcomes

8 New Faculty Members BIOMEDICAL IMAGING & INSTRUMENTATION

Shu Jia Assistant Professor Ph.D., Princeton University Postdoctoral Fellow, Harvard University

The Jia Laboratory works on super-resolution optical microscopy, developing and applying advanced biophotonic tools to study complex, dynamic biological systems at the nanometer scale. Specifically, our research aims to invent a host of methods that enable the extraction of structural, molecular and functional information from intact tissues and organisms, including optical wavefront engineering, single-molecule biophysics, adaptive optics, phase microscopy, large-data processing, advanced instrumentation, nano-fabrication, etc. These projects employ interdisciplinary knowledge across physics, engineering and biology. In collaboration with other researchers, we hope our technologies would provide new insights and solutions to challenges in biological and ultimately clinical research.

BIOMATERIALS & REGENERATIVE TECHNOLOGIES

Athanasios Mantalaris Professor Ph.D., University of Rochester

My research interests lie in the areas of stem cell bioprocessing, tissue engineering and mammalian cell bioprocessing. Our laboratory, in collaboration with others, is seeking to develop a novel monitoring modality that allows the systematic development of clinically relevant culture systems and methodologies, which control and regulate stem cell self-renewal, expansion, differentiation, and death. A breakthrough will lead to the engineering of reproducible, well-characterized, regenerated tissues and organs for clinical applications. In the area of tissue engineering, we are seeking to provide integrated solutions to tissue engineering problems working closely with material scientists and modelers to develop suitable scaffolds and culture systems for a variety of applications ranging from bone marrow, bone, cartilage, pneumocytes and cardiomyocytes, as well as developing ex vivo models for disease states, such as leukemia. Lastly, our research program sets out to integrate modelling, experiment design and validation, and control and optimization into a single framework that would lead to increased productivity, regulated product quality, and reduced costs for mammalian cell culture systems.

SYNTHETIC BIOLOGY AND GENE THERAPY

Karmella Haynes Associate Professor Ph.D., Washington University St. Louis Postdoctoral Fellow, Davidson College Postdoctoral Fellow, Harvard Medical School

My research aims to determine how the intrinsic properties of chromatin, the DNA-protein structure that packages eukaryotic genes, can be manipulated to control developmental processes in human cells and tissues. My overarching vision is a leap forward in the efficacy and flexibility of eukaryotic genome engineering, supported by new approaches to epigenetic control. I believe that approaching the genome as a nucleoprotein complex, rather than as â&#x20AC;&#x2DC;nakedâ&#x20AC;&#x2122; DNA, will support this advance. My lab focuses on the following goals: (i) design and delivery of histone-binding proteins that control gene expression, (ii) reprogramming cancer gene expression through broad chromatin disruption, and (iii) manipulating chromatin to make genome editing more robust and reliable.

CARDIOVASCULAR ENGINEERING

Sung Jin Park Assistant Professor Ph.D., Stanford University Postdoctoral Fellow, Harvard University

We are interested in elucidating how biological systems coordinate the hierarchical structures and functions of their individual components in order to produce emergent physical behaviors, and how disrupting this coordination potentiates disease. Our lab seeks to design, build, and test a hierarchy of biohybrid systems capable of reproducing the targeted behaviors. Our primary interest is coordinated activation and contraction of tissue- and organ-level cardiac and skeletal muscle systems. To pursue this goal, we focus on the development of biohybrid fabrication methods and measurement systems through the combined application of genetic tools, induced pluripotent stem cells, tissue engineering, microfabrication, electronics, optics, and feedback control. The resulting findings and technical developments will be translated into various applications such as (1) stem cell-based functional assays for personalized disease diagnosis and treatment and (2) new types of biohybrid actuators for creating biological autonomous systems.

CARDIOVASCULAR ENGINEERING

Vahid Serpooshan Assistant Professor Ph.D., McGill University Postdoctoral Fellow, Stanford University

Our laboratory uses a multidisciplinary approach to design and develop micro/nano-scale tissue engineering technologies with the ultimate goal of generating functional bioartificial tissues and organs. Reaching this goal requires the skills and expertise from several disciplines including cell biology, medicine, nanotechnology, biochemistry, and materials science and engineering. Current projects in my lab include: bioengineering iPSC-derived, functional cardiac tissues, via 3D bioprinting technology for in vitro disease modeling and drug screening; engineering cardiac patch systems to regenerate damaged myocardium in murine and swine models of ischemic heart injury; and 3D bioprinting-based liver and bone tissue engineering.

ENGINEERING EDUCATION

Cristi Bell-Huff Lecturer Ph.D., Purdue University

Cristi Bell-Huff is part of the team working on implementing innovative pedagogy in engineering education at Georgia Tech and Emory University within the Coulter Department. As such, her work focuses on curriculum design and development, teaching, and engineering education research. Her research interests include the effects of innovative pedagogy on the development of engineering students’ mindset, engagement, retention, and professional formation as engineers. Within BME, she is working on integrating the use of reflection, storytelling, and entrepreneurially minded learning throughout the curriculum.

EDUCATIONAL SCIENCE & INNOVATION

Veronica van Montfrans Todd Fernandez Lecturer Ph.D., Purdue University

My research interests are focused on the interrelationship between engineering education practice and the theories of knowledge of engineering students and faculty. As the boundaries of engineering change what we teach as engineering must change to keep pace. That ongoing change has led to an increased focus on design, entrepreneurship, reflection, ethics, team work, and professional skills of all types. However, those new content areas also bring with them assumptions about the nature of knowledge and knowing (i.e., epistemologies) from their respective fields. When educators and engineering students enter the classroom the assumptions of those new areas of content begin to interact with the theories of knowledge in a shared construction of knowledge. My research explores these intersections and their implications for learning using both quantitative and qualitative research tools. It primarily arises from a critical epistemological perspective and theories of communicative action.

Director of Learning Sciences Innovation and Research Ph.D., Virginia Tech Postdoctoral Fellow, Virginia Tech

My research focuses on defining and refining the cognitive component of social justice scholarship. The goal of defining this component separately from its content and activism is to allow for easy transferability from one content to another with the idea that the learner processes new information through the lens of “who has access and who doesn’t” and “who is impacted both positively and negatively, and who isn’t.” This makes innovative ideas, such as the ones here at BME, develop with a social justice mindset so that the innovator is proactive rather than reactive to potential injustices of their design.

Faculty Major Awards Robles Wins Prestigious NSF CAREER Award

Haider Named Sloan Fellow

Francisco Robles, assistant professor in the Coulter Department, won a Faculty Early Career Development (CAREER) Award from the National Science Foundation. Robles’ award will provide support for a newmolecular imaging technique.

Bilal Haider, assistant professor in the Coulter Department, is among the 126 outstanding U.S. and Canadian researchers receiving 2018 Sloan Research Fellowships. The fellowships, awarded by the Alfred P. Sloan Foundation since 1955, honor early-career scholars who, “represent the very best science has to offer,” says Sloan President Adam Falk. “The brightest minds, tackling the hardest problems, and succeeding brilliantly—Fellows are quite literally the future of twenty-first century science.”

The goal of his work is to gain a better understanding of the molecular and structural composition (so-called phenotypical “common-denominators”) of primary tumors that metastasize as a means to improve tumor staging. To accomplish this task, he will develop a novel optical microscopy technique, ultraviolet hyperspectral interferometric (UHI) microscopy, that probes unique endogenous absorptive and scattering properties of cells and tissues in the deep ultraviolet region of the spectrum. Robles is also a recipient of a NIH R21 grant entitled, “Stimulated Raman scattering spectroscopic optical coherence tomography (SRSSOCT) for label-free molecular imaging of brain tumor pathology.”

Singer Named Packard Fellow Annabelle Singer, assistant professor in the Coulter Department, was named as one of 18 recipients of the prestigious 2017 Packard Fellowships for Science and Engineering by the David and Lucile Packard Foundation. Singer sees the fellowship as validation for her research, which employs novel techniques to identify and restore failures in brain activity that lead to memory impairment. “We’re in the midst of a big plan to expand neuroscience, and I hope this will help get the word out that it’s a great place to do cutting edge neuroscience and neuroengineering,”she said. She is also the recipient of an NIH R01 grant entitled “Non-invasive methods to drive neural activity with millisecond precision and to recruit the brain’s immune cells.” Annabelle Singer is also the recipient of an NIH R01 award entitled “Non-Invasive Methods to Drive Neural Activity with Millisecond Precision and to Recruit the Brain’s Immune Cells.”

Haider’s research goal is to identify cellular and circuit mechanisms that modulate neural responsiveness in the brain’s cerebral cortex, using a variety of advanced electrical and optical techniques to record, stimulate, and the interpret the activity of specific neuronal sub-types. Haider is also the recipient of a National Institute of Neurological Disorders and Stroke (NINDS) R01 grant entitled, “Directly measuring synaptic and population coupling in cortex during perception;” a NIH Brain Initiative (NINDS) R01 grant entitled, “Circuit and Synaptic Mechanisms of Visual Spatial Attention,” and a Simons Foundation Autism Research Initiative (SFARI) Explorer award.

Dahlman named to MIT Technology Review’s Innovators Under 35 List James Dahlman, assistant professor in the Coulter Department, has been named to MIT Technology Review’s prestigious annual list of Innovators Under 35. Dahlman is a biomedical engineer working at the interface of nanotechnology, gene editing, and genomics. His lab develops novel ‘big data’ technologies and applies them to the study of nanomedicine. One such application is the use of DNA barcodes to track thousands of nanoparticles directly in vivo; typically, labs will study only a few nanoparticles in vivo. His research will greatly accelerate improved drug delivery using nanoparticles.

This page: Qiu, Dyer Opposite page, clockwise from top: Robles, Dahlman, Haider, Singer

Peng Qiu wins grant from Chan Zuckerberg Initiative Peng Qiu is an associate professor in the Coulter Department, and now he’s also part of the Chan Zuckerberg Initiative (CZI). Qiu will be supporting the Human Cell Atlas project, a global effort to map every type of cell in the healthy human body as a resource for studies of health and disease. Qiu’s main research interests are in bioinformatics and computational biology, focusing on machine learning big data, genomics, and single-cell analytics. Peng Qiu is also named an ISAC Marylou Ingram Scholar by the International Society for Advancement of Cytometry (ISAC).

Dyer Tapped by Allen Institute for Brain Science Eva Dyer, assistant professor in the Coulter Department, is part of the newest cohort of Next Generation Leaders, as selected by the Allen Institute for Brain Science. Dyer’s research interests lie at the intersection of machine learning, optimization, and neuroscience. She develops computational methods for discovering principles that govern the organization and structure of the brain, as well as methods for integrating multi-modal datasets to reveal the link between neural structure and function. Eva Dyer is also the recipient of an NSF Computer and Information Science and Engineering Research Initiative (CRII) award for her gran¬t entitled, “Using Large-Scale Neuroanatomy Datasets to Quantify the Mesoscale Architecture of the Brain.”

Faculty Award Highlights

Ed Botchwey named as one of Georgia Tech’s Faces of Inclusive Excellence Honorees, and inducted as Fellow of American Institute for Medical and Biological Engineering (AIMBE). Hee Cheol Cho and his “Messenger RNA-based Biological Pacemaker” wins Innovation of the Year award from Emory University’s Office of Technology Transfer during their 12th Annual Celebration of Technology and Innovation. James Dahlman honored for Department Excellence in Teaching award given by the Biomedical Enginering Student Advisory Board. Jaydev Desai named IEEE Fellow, and inducted as Fellow of American Institute for Medical and Biological Engineering (AIMBE). Erik Dreaden receives Emory School of Medicine Faculty Excellence MilliPub Club award Sathya Gourisankar inducted as Fellow of American Institute for Medical and Biological Engineering (AIMBE).

Hanjoong Jo receives the Bernard and Joan Marshall Distinguished Award from the British Society of Cardiovascular Research.

Cassie Mitchell named as Emory University’s Winship Cancer Institute Winship 80 Honoree.

Charlie Kemp receives Georgia Tech’s 1940 Course Survey Teaching Effectiveness award.

S. Balakrishna Pai receives the Georgia Tech’s Undergraduate Educator Award.

Gabe Kwong receives Georgia Tech’s Center for Teaching and Learning/BP America Junior Faculty Teaching Excellence Award. Wilbur Lam’s new company Sanguina along with their new FDA approved AnemoCheck product won as Significant Event of the Year from Emory University’s Office of Technology Transfer during their 12th Annual Celebration of Technology and Innovation. Michelle LaPlaca named a President-Elect for the National Neurotrauma Society Joe Le Doux named as one of Georgia Tech’s Faces of Inclusive Excellence Honorees. Susan Margulies receives Emory School of Medicine Faculty Excellence MilliPub Club award

Machelle Pardue inducted as Fellow of American Institute for Medical and Biological Engineering (AIMBE). Krishnendu Roy receives Georgia Bio’s Deal of the Year award for Georgia Tech’s new NSF Engineering Research Center for Cell Manufacturing Technologies (CMaT), and receives a new three year $1.8 Million grant in Advanced Biomanufacturing from the FDA. Johnna Temenoff appointed to the Carol Ann and David D. Flanagan endowed professorship. Younan Xia receives several honors including the Materials Research Society (MRS) Medal, the NSF Special Creativity award, and was included in the Inaugural Class of Hall of Fame Advanced Materials.

Celebrating Faculty Receiving their First Major Grant Erin Buckley: DoD grant entitled “Linking cerebral hemodynamics and neuroinflammation to Alzheimer’s pathology in repetitive mild traumatic brain injury”; NIH R21 grant entitled “Microvascular Cerebral Blood Flow Measured with Diffuse Correlation Spectroscopy in Children with Sickle Cell Disease”; NIH R21 grant entitled, “Objective biomarkers of cognitive outcome in repetitive mild traumatic brain injury”

Bilal Haider: NIH RO1 entitled “Directly measuring synaptic and population coupling in cortex during perception”

Eva Dyer: NSF grant entitled “Using LargeScale Neuroanatomy Datasets to Quantify the Mesoscale Architecture of the Brain”

Chethan Pandarinath: NSF grant entitled “Discovering Dynamics in Massive-scale Neural Datasets Using Machine Learning.”

Yonggang Ke: Awarded NSF grant through the Semiconductor Synthetic Biology for Information Processing and Storage Technologies (SemiSynBio) program to create DNA-based electrically readable memories

Francisco Robles: NIH’s National Cancer Institute Innovative Molecular Analysis Technologies (IMAT) R21 grant entitled “Stimulated Raman Scattering Spectroscopic Optical Coherence Tomography (SRS-SOCT) for Labelfree Molecular Imaging of Brain Tumor pathology” Annabelle Singer: NIH R01 entitled “Noninvasive Methods to Drive Neural Activity with Millisecond Precision and to Recruit the Brain’s Immune Cells”

Georgia Tech Faces of Inclusive Excellence Honorees

Ed Botchwey, Joe Le Doux, Brenda Morris These biomedical engineering faculty and staff were recognized for their commitment to advancing a culture of inclusive excellence at Georgia Tech and who have distinguished themselves in their research, teaching, and service.

Making Dreams Come True Launching careers in cell therapy industry and research

eorgia Tech along with the University of Georgia and University of Wisconsin hosted undergraduate students from schools across the country to participate in graduate level research over the summer.

Students got research experience through the National Science Foundation’s Research Experience for Undergraduates (REU) program, and were placed within the NSF Engineering Research Center for Cell Manufacturing Technologies (CMaT) headquartered at Georgia Tech. Students have traditionally not received much research-based experience until they enter graduate school. The NSF’s REU effort is helping to change that by giving undergraduates an opportunity to work in advanced research labs alongside top graduate students and pioneering researchers in a broad range of fields. By giving them an idea of what it’s like to participate in the development of cutting-edge therapies and new technologies, the program is helping develop the next generation of research leaders. “Educational programs at all levels are critical, of course, and the REU program bringing undergraduates into CMaT labs is important for introducing these students to the excitement of

new cell therapies and cell manufacturing,” said Aaron Levine, CMaT’s co-director for workforce development and a professor in Georgia Tech’s School of Public Policy. “Developing the future workforce has been identified as a critical issue for cell manufacturing to succeed. The CMaT workforce programs are critical to our success — and for the industry to reach its full potential.” The students applied for the REU at CMaT and were assigned both a university principal investigator and a mentor for the summer. Beyond the lab experiences, the students learn collaboration, networking and other key skills. “This is a unique and impactful REU program focused on cell manufacturing research that has successfully engaged an impressive cohort of students, many from underrepresented groups in STEM,” said Mary Poats, REU program manager in NSF’s Division of Engineering Education and Centers. “The students are engaged early on in state-of-theart ERC research and innovation activities that are directed toward a goal of curing disease and illnesses throughout the world. It is rewarding to hear these students passionately describe how being a part of CMaT’s summer REU program has so positively impacted their desire to further pursue related engineering and

science academic studies, along with careers in the health care industry.” For David Frey, a Georgia Tech second-year student majoring in biomedical engineering, working in the lab of Krishnendu Roy, CMaT executive director and Robert A. Milton Chair, unlocked a “dream come true.” Frey worked on a microfluidics project that could lead to improvements in the way cells are cultured. The technology could also help match therapies to a patient’s specific disease characteristics. “It’s truly been a dream come true,” he said. “I’ve always wanted to be in the lab all day. But being in school, I could never do that. This program definitely helps you immerse yourself in the research you are doing.” As with others in the program, Frey was excited about being part of the cell manufacturing initiative in its early stages. “It’s exciting being a pioneer with this specific technology,” he said. “Every day you want to see what the final product will look like. You want to see that the technology is being used for medical purposes. This could potentially help thousands of people someday.”

NIH ESTEEMED Program Expands Pipeline Diversity Georgia Tech one of first universities in the nation to embark on diversity-building STEM education program orientation meeting on Tuesday, Sept. 11, are: Thiago Esslinger, biochemistry; Nathan Haileyesus, biomedical engineering; Zaria Hardnett, neuroscience; Cayla Jones, chemistry; Kaiya Mitchell, biomedical engineering; Alexandria Neal, chemistry; Trey Quinn, computer science; Giancarlo Riccobono, biomedical engineering; Clinton Smith, biomedical engineering; Rhiannon Wackes Meléndez, biomedical engineering.

Platt

These students were part of an ESTEEMED required ‘Summer Bridge Program,’ helping to ease the transition to college life, something Platt experienced when he was a new student at Morehouse College, and the inspiration for the grant he submitted to NIH almost two years ago.

en freshmen are blazing a new trail and making history at Georgia Tech as the inaugural cohort of students in one of the nation’s first two ESTEEMED programs, supported by the National Institutes of Health (NIH) and designed to increase diversity in the biomedical research workforce. “It’s exciting that they only chose two programs from this first round of funding, and we are one of them,” said Manu Platt, an associate professor in the Coulter Department of Biomedical Engineering, who is directing the program. The other ESTEEMED program is also based in Georgia at Savannah State University, the oldest HBCU (Historically Black College and/or University) in the state. “I think this speaks highly of Georgia Tech, its commitment to diversity, and the historic record we have of demonstrating this commitment for a new and highly experimental program,” added Platt, a researcher in the Petit Institute for Bioengineering and Bioscience, whose co-investigators in the ESTEEMED program are Wendy Newstetter and Cassie Mitchell, both faculty members of the Coulter Department. ESTEEMED, which stands for ‘Enhancing Science, Technology, EnginEering, and Math Educational Diversity,’ is a five-year, $1.7 million program funded by the National Institute of Biomedical Imaging and Bioengineering (NIBIB, a division of NIH) that supports early preparation in undergraduate education in STEM fields. According to Platt, the goal is to have an impact on groups historically underrepresented in STEM, groups that include racial/ethnic minorities, people with disabilities, those from underprivileged backgrounds, and intersections of these categories. The first cohort of students, who gathered for a fall semester ESTEEMED

“I was in a pre-freshman summer program at Morehouse and I equate a lot of my success with that,” said Platt, who finished high school in Delaware. “I came down the summer before my freshman year and met the best friends of my life. It was very helpful, something I didn’t realize at the time – you do it because it’s part of your scholarship, but then you realize later what a big impact it had.”

Newstetter

Mitchell

He’s hoping the scholars embarking on the ESTEEMED journey will realize the impact sooner. Participants are expected to eventually enter an advanced honors program for juniors and seniors, which aims to prepare them for doctoral programs in biomedical research fields. “This is a new program, a new model, and we want to have an early impact that can be sustained,” Platt said. “We want that jump from high school to college to be great, so that they land with excellent GPA’s. And we want to break down the barriers between students and faculty, so that they see faculty as their friends.” Faculty lunches with ESTEEMED scholars will help break down those barriers, and the students’ laboratory research experiences will be enhanced by the participation of grad students and postdocs who will serve as mentors. Platt also expects the students’ participation in science conferences and workshops will provided a critical added value. “Those experiences will expose them to difference science and scientists,” he said. “It will spark their imaginations and help them realize that a career in biomedical research is an excellent idea.”

Mayo Sponsored Drug Delivery Project Wins NIH NIBIB DEBUT Award

team of students from the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University and the Woodruff School of Mechanical Engineering at Tech took third place in the Design by Biomedical Undergraduate Teams (DEBUT) Challenge.

The team, now called Ethos Medical (formerly known as Neuraline), were among five innovative teams whose projects, all focused on improving global health, won DEBUT awards. DEBUT is a biomedical engineering design challenge for undergraduate students, managed by the National Institute of Biomedical Imaging and Bioengineering (NIBIB), part of the National Institutes of Health (NIH), and VentureWell, a non-profit that cultivates revolutionary ideas and promising inventions. The NIBIB prizes were awarded based on four criteria: the significance of the problem being addressed; the impact of the proposed solution on potential users and clinical care; the innovation of the design; and the existence of a working prototype. In selecting its prizes, VentureWell considered two additional criteria: market potential and patentability. The $65,000 in prizes will be awarded during a ceremony at the annual Biomedical Engineering Society (BMES) in Atlanta this October. “This was a great experience for us as our project continues to evolve,” said Ethos Medical’s Cassidy Wang, who graduated from the Coulter Department this past spring and whose team took third place, winning $10,000. Their patent-pending handheld tool is designed to improve placement for lumbar punctures (the process of taking fluid from the spine in the lower back with a hollow needle, typically for diagnostic purposes). When this Mayo Clinic sponsored team competed in the Capstone Design program last spring, and in the DEBUT challenge, it was called Neuraline, and its focus was on epidural anesthesia placement, which allowed physicians to identify optimum entry into specific anatomical spaces using bioelectrical impedance analysis. The idea is still basically the same – optimum needle placement. But Wang says the team has gone back to its initial focus, lumbar punctures, after further research. “Oddly enough, lumbar puncture was where our project originally started. The market opportunity there is high,” Wang explained. “We found that hospitals lose about $450 million a year because of

Left to right: Lucas Muller, Cassidy Wang, Dev Mandavia

failures in lumbar punctures. There is a real need.” In addition to Wang, Ethos Medical team members include Coulter Department senior Dev Mandavia, and recent grads from the Woodruff School of Mechanical Engineering at Tech, Lucas Muller and Alec Bills (now in grad school at Carnegie Mellon University). While the team is now taking a slightly different path with its device, the core problem remains basically the same. Different tissue types exhibit different electrical impedances that are measured by the device’s electronics module, which enables realtime tissue identification. “When lumbar procedures fail, 28 to 35 percent of the time, they have to be rescheduled. That’s the hospital’s cost,” Wang said. “Improving the procedure with a better tool is presents a huge financial incentive for hospitals.” Ethos Medical, which also recently competed for the James Dyson Award and completed the Create X entrepreneurial startup summer program at Georgia Tech, will now focus on perfecting prototypes of its device.

BME Team Takes Home Top Capstone Design Prize BME team Kit Cath took home Georgia Tech’s Capstone Design Expo’s best overall project award and are hoping it opens some doors for them as they approach graduation and look for jobs. The team is made up of biomedical engineering majors Kathleen Jordan, Lemou Tieyam, Diana Yunda, and Alexa Schlein. This winning BME team developed an adaptable catheter for their sponsors in the Interventional Radiology Department at Emory University Hospital Midtown. Inspired by a Slinky, the catheter tip can bend and adjust to the curves in a patient’s vascular system, resulting in a snug fit and greatly reducing the amount of time radiologists have to spend adjusting catheters. It will also reduce the number of catheter exchanges, wasted product, procedure lengths, costs, and patient discomfort. Everyone on the team is interested in pursuing careers in the medical device field.

The winning team in the BME category was NICUties for their neonatal nasogastric tube holder. Each year 500,000 newborns are admitted to the NICU in the US, with the majority requiring a feeding tube. Unplanned extubation, which occurs when a child pulls out their tubing, is the 4th major cause of adverse events in the NICU. Their device named FixedFeed secures and places the nasogastric tubing out of reach to prevent unplanned extubation, increase neonatal outcomes, and decrease stress of NICU nurses. The team members are Erika Plogstedt, Kylee McLain, Cecille Canary, and Cristina Quintero.

Chris Lee Founded Vertera Spine NuVasive has now purchased the company

Chris Lee earned his Ph.D. in biomedical engineering in the spring of 2012 from the Wallace H. Coulter Department at Georgia Tech and Emory University. During his time as a doctoral student, he met entrepreneurs, engineers, and professors that shared his desire of translating medical research into new therapies. In 2013, Lee founded Vertera Spine as president and CEO, the company specialized in the production of Porous PEEK spinal implants, an innovative technology that has revolutionized the way implants are being integrated with the body. This technology was invented and refined with the help of Georgia Tech faculty, some of whom are cofounders of the company. At Vertera, they developed a highstrength, porous polymer that mimics the mechanics and topography of bone. These unique properties allow orthopedic and spinal implants to directly integrate to the body. Their technology was the first porous polymer to be approved by FDA for a load-bearing application. The company started with public grants and private investment, and in three years received FDA approval for their first device. In 2017, NuVasive, a medical device company focused on transforming spine surgery with minimally disruptive, procedurally-integrated solutions, purchased Vertera Spine. Under NuVasive, Vertera Spine’s porous PEEK technology is poised to transform spinal fusion surgery as a key element of the company’s portfolio of scientifically advanced materials. Lee says the new implants can speed surgical recovery from six to 12 months to six to 12 weeks. “Since founding the company in 2013, our goal has been to help reach more surgeon customers and their patients with this disruptive technology. Together, we will now be able to better serve the market and change the lives of patients around the world,” said Lee.

“Since founding the company in 2013, our goal has been to help reach more surgeon customers and their patients with this disruptive technology. Together, we will now be able to better serve the market and change the lives of patients around the world.” Chris Lee

BME Ph.D. Student Wins Two National Competitions, then Becomes CTO at Startup This past year, Robert Mannino, a Ph.D. student in the Coulter Department of Biomedical Engineering, won, not one, but two national prizes.

that we had won the Cisco prize. We felt that our invention was truly a global product with the potential to help many people around the world.”

In his first competition, held in Boston and hosted by Massachusetts General Hospital Ambulatory Practice of the Future, Mannino won the 2017 Student Technology prize for Primary Healthcare. Mannino and his team at Georgia Tech won the first-place prize and $100,000 for their innovative work to develop non-invasive technology (a smart phone app) for patients’ self-management of anemia.

Mannino worked in the lab of Wilbur Lam, associate professor of BME and a researcher in the Petit Institute for Bioengineering and Bioscience. It’s research that hits close to home for Mannino, who was born with a rare genetic blood disorder, thalassemia major, which causes anemia and requires him to receive a blood transfusion every month. Basically, says Lam, “his Ph.D. is centered on developing new diagnostics for his own disease.”

This annual national competition encourages graduate and undergraduate engineering students to direct their creative skills toward the needs of primary care – innovations that have a substantial potential to improve the delivery of care, whether they be technologies, instrumentation, devices, or systems. The technologies of particular interest improve access to medical care, leverage the skills of caregivers, automate routine tasks, increase workflow efficiency, support patients with chronic disease, increase compliance with protocols, reduce error, or augment the physician-patient relationship. In his second competition, Mannino teamed with Prateek Mittal, an MBA student, to compete at the 17th annual Rice University Business Plan Competition held April 5-8, in Houston, Texas. The competition is the world’s richest and largest graduate-level student startup competition with submissions from close to 400 student teams from around the world.

He’s already completed an initial clinical assessment of the system, which uses smartphone photos of the patient’s fingernails for diagnosis. He has invented a non-invasive, low-cost, home test for anemia. Globally, anemia affects 1.6 billion people. In addition to honing his smart phone app, Mannino, who completed his Ph.D., has joined Sanguina. The company is a biomedical startup founded in 2014 focused on the development and distribution of simple-to-use and standalone pointof-care blood diagnostics. Mannino now serves as their chief technology officer and leads development of their non-invasive technologies.

Here, Mannino and Mittal won the Cisco Global Problem Solver Prize and a monetary award of $100,000. The win was again centered around Mannino’s smartphone app that measures blood hemoglobin levels. Mannino teamed with Mittal, an MBA student in the Scheller College of Business, joining forces in the business school’s Ti:GER program. TI:GER teams work together in the classroom and research lab to learn how to advance early-stage research into real business opportunities. “This competition was almost overwhelming—it was massive and intense. Our team, Lunula Health, gave four separate pitches to investors, venture capitalists and scientists,” said Mannnio. “We were so excited and surprised when we learned

Research Focus Areas & Facilities Outstanding Medical Facilities and Resources

Neuroengineering

Immunoengineering

Cardiovascular Engineering

Drug Delivery Cell Therapy

Biomedical Imaging & Instrumentation

Biomedical Informatics and Systems Modeling

Biomedical Robotics

Biomaterials

Cancer Technologies

Regenerative Technologies

• • • • •

Yerkes Vaccine Center Centers for Disease Control and Prevention Children’s Healthcare of Atlanta Grady Memorial Hospital Winship Cancer Institute

National Institutions Located Nearby: Centers for Disease Control and Prevention (HQ) The American Cancer Society (HQ) Research facilities: Atlanta Clinical Research Network Sites Center for Advanced Brain Imaging Emory Pediatrics Building Emory School of Medicine and Research Centers Health Sciences Research Building Marcus Autism Center Marcus Nanotechnology Building Molecular Science & Engineering Building Parker Petit Institute for Bioengineering and Bioscience Roger A. and Helen B. Krone Engineered Biosystems Building Technology Enterprise Park U.A. Whitaker Building Wayne Rollins Research Center Whitehead Biomedical Memorial Building Winship Cancer Institute Woodruff Memorial Research Building Yerkes Regional Primate Research Center

Teaching facilities: Atlanta Veterans Affairs Medical Center Egleston Children’s Hospital at Emory University Emory University Hospital Emory University Hospital Midtown; Grady Memorial Hospital Wesley Woods Geriatric Hospital

External Advisory Board External advisory board members provide an important outside perspective that is essential to maintaining the impactful relevance of our programs to industry. They play a significant role in vetting programs designed for students, alumni, and corporate constituencies to ensure we maintain the highest quality standards in our curriculum, practice and outreach.

Nancy Allbritton, M.D., Ph.D. Professor and Chair UNC/NC State Rafael Andino, M.S., M.B.A. Vice President, Engineering & Manufacturing Clearside Biomedical, Inc. Gilda Barabino, Ph.D. Dean and Berg Professor The Grove School of Engineering at The City College of New York Walt Baxter, Ph.D. Sr. Principal Scientist Medtronic

Virginia L. Giddings, Ph.D Sr Director, Advanced Technology and Innovation Stryker Neurovascular Stacy Kromenhoek Boston Scientific Global Innovation Sr. Program Manager Jeff Lane, Board Chair Managing Partner Messner Lane Capital LLC

Robert (Bob) Sah Ph.D. Professor, Department of Bioengineering University of California, San Diego Erin M. Spinner, Ph.D. Manager Advanced Imaging and Training Sue Van President, Emeritus Member Wallace H. Coulter Foundation

Chris Lee, Ph.D. Medical Technology Entrepreneur and Angel Investor

Vivek Bhatt, Ph.D. CTO GE Healthcare

Brian Lehman Division Vice President- Arrhythmia Therapies Abbott

Kelly Bolden, M.D., FACS Plastic and Reconstructive Surgery Washington, DC

Brad Miller, M.D. Chief Medical Officer and SVP Ciperhealth

Elias Caro VP Technology Development Wallace H. Coulter Foundation

Angela Gill Nelms Chief Operating Officer Florence Healthcare

David Frakes, Ph.D. Technical Project Lead Google

James (Jim) Ross, Ph.D. Chief Technical Officer Axion Biosystems

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The Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University affirms our institutions’ efforts to increase equity, diversity, and inclusion on our campuses. We strive to create a welcoming, diverse and inclusive environment that values, celebrates, and respects the individual and communal differences that make us human, and aspire to cultivate global leaders in engineering and medicine who are champions of inclusive excellence.

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