Written by Abby Vogel

When Georgia Tech President Wayne Clough broke ground on the first building of the new Biotechnology Complex in May 1998, the shovel heralded more than just new brick and glass.

The four new structures built around the quadrangle became the physical manifestations of one of the most dramatic changes in Georgia Tech’s nearly 125-year history. The 800,000 square feet of new buildings represent the convergence of bioscience and engineering, providing the foundation for a $27 million biomedical engineering research program that is now the second largest among U.S. colleges and universities, according to National Science Foundation statistics for 2006.

The centerpiece academic department is the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University.

Created in 1997, the joint department has emerged as a vibrant and innovative center for education and research in biomedical engineering in which teams of highly interdisciplinary researchers collaborate and network across a global environment. The department combines the design and problem-solving skills of engineering with the medical and biological sciences to improve patient health care and the quality of life for healthy individuals.

Marking its 10th anniversary this year, the Coulter Department continues to build its interdisciplinary programs to tackle the challenges of the 21st century, including cardiovascular disease, nerve injuries, neurological disorders, bone loss and cancer. This article describes a sampling of the department’s research.

Charting Blood Flow in 3-D

For every 1,000 babies born in the United States, two are born with just one functional heart ventricle. Their early years are filled with surgeries that aim to restructure circulation to pump blood directly to the lungs without the heart’s help.

To allow surgeons to get a detailed look at a child’s heart structure before these surgeries, Ajit Yoganathan, a Regents’ Professor and The Wallace H. Coulter Distinguished Faculty Chair in Biomedical Engineering, has developed personalized three-dimensional models of the heart to show a surgeon how well blood would flow through proposed post-surgery configurations. Each model is created using data from a series of magnetic resonance imaging scans of the child’s heart taken at different times in the cardiac cycle.

“We work very closely with the cardiologists and cardiac surgeons to help with surgical planning,” says Yoganathan. “With a better understanding of each child’s unique heart defect, surgeons can improve the surgery outcome and recovery time.”

Yoganathan collaborates with Emory University, Children’s Healthcare of Atlanta, Children’s Hospital of Philadelphia and Children’s Hospital Boston on this project, which is funded by the National Institutes of Health.

Another team of researchers is using magnetic resonance imaging scans to predict where atherosclerotic plaques will form and rupture in arteries based on fluid flow. Plaques form in artery walls because of cholesterol build-up. When they rupture, they can block blood vessels, leading to heart attack or stroke.

“We believe plaques form where blood flow slows down in an artery, maybe due to bends or branches in the artery that cause an eddy to form,” says John Oshinski, an assistant professor in the Coulter Department and Emory’s Division of Radiology.

To find these areas of slower flow, Oshinski collects magnetic resonance images to visualize blood flow patterns in arteries. From the images, Jin Suo, a Coulter Department research engineer, and Don Giddens, dean of the Georgia Tech College of Engineering, Lawrence L. Gellerstedt, Jr. Chair in Bioengineering and Georgia Research Alliance Eminent Scholar, develop computational fluid mechanics models to show specific flow patterns near the artery walls, locations where plaque is likely to form.

Because heart disease can take decades to develop, the researchers plan to monitor flow patterns long-term to investigate how early plaques can be detected and what type of blood flow is present where the plaques form.

W. Robert Taylor, a professor in the Coulter Department and Emory’s Division of Cardiology, and Ray Vito, a professor in the Georgia Tech School of Mechanical Engineering and vice provost of graduate and undergraduate studies, are collaborators on this project funded by the National Institutes of Health.

In related research, Hanjoong Jo, the Ada Lee and Pete Correll Professor in Biomedical Engineering, has shown that several genes are over-expressed when arteries are exposed to abnormal, nonlinear flow patterns. Expression of these genes leads to inflammation and hypertension, which increase the possibility of plaque building up inside the vessels. With funding from the National Institutes of Health, the Wallace H. Coulter Foundation and the American Heart Association, Jo is developing drugs that inhibit these genes to treat inflammation, atherosclerosis and hypertension.

Rebuilding the Heart

The inability of heart muscle to regenerate in the body provides a major obstacle to the clinical treatment of heart attacks – one that researchers in the Coulter Department are trying to overcome.

Todd McDevitt, a Coulter Department assistant professor, is developing new strategies to turn embryonic stem cells into specialized heart muscle cells called cardiomyocytes, which may repair damaged heart muscles. With funding from the American Heart Association, McDevitt is collaborating on this project with Samuel Dudley, a professor of medicine in the Section of Cardiology at the University of Illinois at Chicago.

To be successful, embryonic stem cells must differentiate into the targeted cell type in an efficient, controlled and repeatable fashion. McDevitt’s group aims to define and control the environmental cues that regulate the fate and function of the cells.

To produce a more homogeneous population of cells, McDevitt developed a method to incorporate polymer microspheres into embryoid bodies, which are aggregates of cells derived from embryonic stem cells. He can encapsulate small molecules, growth factors and proteins inside the microspheres to direct the stem cells to become the targeted cell type. This research is funded by the National Science Foundation.

Niren Murthy and Michael Davis, both Coulter Department assistant professors, have taken a different approach to improving the way physicians treat heart attacks. They have shown that injecting drug-containing polyketals during a heart attack can improve treatment. Because these biodegradable polymer nanoparticles do not produce inflammation-causing acid when degraded, the body allows intracellular delivery and sustained release of the drugs.

With funding from the National Institutes of Health, the researchers showed improved cardiac regeneration in rats and mice when polyketals were used to deliver drugs during a heart attack. Murthy is also investigating the use of these polyketal particles to facilitate drug treatment of acute lung injury, acute liver failure and lung fibrosis.

Reconnnecting Nerves

Motor vehicle accidents, electrical burns, gunshot wounds, cutting incidents and surgical procedures can sever or tear peripheral nerves to varying degrees. Sometimes, these peripheral nervous system injuries result in a gap between two peripheral nerve stumps. Coulter Department professor Ravi Bellamkonda has developed a device for nerve repair that is a potential alternative to the clinical standard of transplanting nerve segments from another part of the body.

In collaboration with Satish Kumar, a professor in Georgia Tech’s School of Polymer, Textile and Fiber Engineering, and Art English, a professor in Emory’s Department of Cell Biology, Bellamkonda has demonstrated that thin polymer films made of aligned nanometer-diameter fibers provide topographical cues to stimulate regeneration without any growth-promoting proteins. Funding for this research was provided by the National Institutes of Health and by the National Science Foundation, through the Georgia Tech/Emory Center for the Engineering of Living Tissues.

Unlike peripheral nervous system injury, injury to the central nervous system is not followed by extensive regeneration because of the hostile growth environment caused in large part by the injury. Central nervous system injuries are commonly the result of motor vehicle accidents, sporting accidents, falls and acts of violence that cause a traumatic brain or spinal cord injury.

Transplanting stem cells in a bioactive scaffold designed to provide structural and adhesive support while providing survival signaling cues is one strategy that shows promise for replacing the function of missing or damaged neural cells. However, optimization prior to clinical implementation requires expensive and time-consuming in-vivo studies.

“We have developed a three-dimensional culture system of the injured host-transplant interface that can be used to evaluate and optimize tissue-engineered strategies,” says Michelle LaPlaca, a Coulter Department associate professor. “We mimic the forces and deformations that brain tissue would see during an actual injury and then monitor the ability of donor cells to rescue the injured cells.”

With the 3-D neural cell culture, LaPlaca can also evaluate neuroprotective pharmaceuticals targeted to mitigate injury. The 3-D cultures were described in the April 2007 issue of the Journal of Neural Engineering. This research is funded by the National Institutes of Health and National Science Foundation.

Yadong Wang is using a different strategy to encourage the regeneration of damaged central nervous system neurons. A Coulter Department assistant professor, Wang has shown that incorporating neurotransmitters, such as dopamine or acetylcholine, into a biodegradable polymer spurs the growth of neurites, which are projections that form the connections among neurons and between neurons and other cells.

“Regeneration in the central nervous system requires neural activity, not just neuronal growth factors alone, so we thought a neurotransmitter might send the necessary signals,” explains Wang.

The polymer would be implanted at the damaged site to promote nerve regeneration after an injury. It would then degrade as the neural network forms. The research on acetylcholine-based polymers, supported by the National Science Foundation and the National Institutes of Health, was published in the December 2007 issue of Advanced Materials.

The types of scaffolds LaPlaca and Wang propose for nerve regeneration are considered combination products because they contain a mixture of drug, device and/or biologics – which include DNA, cells and proteins in gene therapy, cell therapy and plasma products, respectively. Combination products are increasingly incorporating novel technologies that hold great promise for treating disease and trauma, and advancing patient care.

Two types of combination products are common: tissue-engineered constructs that use a polymer component as a scaffold to deliver or direct cells to restore or replace damaged tissue and vaccine delivery systems that use a polymer as a carrier to enhance the delivery of DNA- or protein-based vaccines to the desired cells.

Julia Babensee, a Coulter Department associate professor, investigates how polymer biomaterials influence immune responses toward the biological component of combination devices. To do this, she investigates how biomaterial contact influences the immune stimulatory capacity of dendritic cells, which traditionally recognize foreign pathogens or “danger signals” and initiate an immune response when they mature.

“Biomaterials that induce dendritic cell maturation and support an immune response are optimal for vaccine delivery systems where protective immunity is sought, whereas biomaterials that inhibit an immune response are desired for tissue-engineered constructs where tolerance is a goal,” says Babensee.

The novel idea is that biomaterials themselves can be used to direct immune responses toward associated biological components. This research is funded by the National Institutes of Health and the National Science Foundation.

With funding from the Arthritis Foundation, Babensee is extending her research to determine the best tissue engineering constructs to implant in joints affected by autoimmune rheumatoid arthritis.

The Complex Brain

Steve Potter, a Coulter Department associate professor, is studying how brains learn, or more specifically, how they acquire memories and behaviors. The process of learning is thought to correspond to changes in the relationships between neurons in the brain, but exactly how those changes are expressed at the network level is not well-understood.

Since it’s difficult to study neuronal networks in vivo, Potter has developed imaging tools to study living neurons while they’re growing and forming connections in a petri dish. The dish contains an array of electrodes embedded in the bottom, which creates a two-way connection between the cells and a computer that records all cellular activity and delivers stimuli.

With funding from the National Institutes of Health, Potter is designing the technology to study drug addiction on a cellular level. The neural interface allows neuron cultures to douse themselves with drugs using a robotic “picospritzer.” Potter studies how the network changes as a response to the chemical self-stimulation.

“This may help explain why former cocaine addicts relapse, but more importantly, we may be able to find ways to cure drug addiction through better understanding of drug action in neuronal networks,” says Potter.

Xiaoping Hu, a Coulter Department professor and Georgia Research Alliance Eminent Scholar in Imaging, and assistant professor Erica Duncan and professor Clint Kilts, both of Emory’s Department of Psychiatry and Behavioral Sciences, are also studying drug addiction, but on the human brain level.

In a recent study funded by the Office of National Drug Control Policy and the National Institutes of Health, they used functional magnetic resonance imaging (fMRI) to show that stress may precipitate relapse in cocaine addiction by activating brain areas that mediate reward processing.

As director of the Biomedical Imaging Technology Center at Emory University, Hu is also using fMRI to assess long-term effects of prenatal alcohol exposure on brain development. This project is in collaboration with Claire Coles, a professor in Emory’s Department of Psychiatry and Behavioral Sciences, with funding from the National Institutes of Health.

With funding from the Atlanta VA Rehabilitation Research and Development Center of Excellence for Aging Veterans with Vision Loss, Hu is collaborating with Ronald Schuchard, an associate professor at Emory University and director of the center, to study elderly brain health. They are currently using fMRI to study structural and functional connectivity in the brain during the progression and treatment of age-related macular degeneration.

Lena Ting, a Coulter Department assistant professor, also conducts research relevant to elderly health by studying the loss of balance that leads to falls, a primary cause of injury and accidental death in older adults.

After the brain’s neural pathways are impaired through injury, age or illness, muscles are deprived of the detailed sensory information they need to perform the constant yet delicate balancing act required for normal movement and standing. With funding from the Whitaker Foundation and the National Institutes of Health, Ting has developed a quantitative model that shows how the nervous system reinvents its communication with muscles after sensory loss.

Assistant professor Lena Ting and graduate student Stacie Chvatal set up a human balance test. (Click image for high-resolution version. Credit: Rob Felt)

“Knowing this information will help in the development of diagnostic and therapeutic tools for balance and movement disorders,” says Ting.

Engineering Solutions for Musculoskeletal Problems

Professor Barbara Boyan uses basic science knowledge to engineer novel approaches for restoring tissues and function for patients suffering from musculoskeletal problems. This effort includes the development of more effective bone graft materials, improved design of dental and orthopedic implants that interface with bone tissues, and methods for delivering cells to sites of injury without the need for invasive surgical procedures.

Boyan also aims to better understand the mechanisms involved in bone and cartilage growth and loss, and conditions such as osteoporosis and osteoarthritis. Estimates suggest that osteopororis, a condition in which bones lose mass, become weak and can break from a minor fall, affects more than 10 million people. Osteoarthritis is a condition in which cartilage is lost from the ends of the bones, resulting in pain and reduced function. It affects most individuals as they age, but is most severe in women over 50.

With funding from the National Institutes of Health, the National Science Foundation, the Department of Defense and Children’s Healthcare of Atlanta, Boyan discovered biochemical differences between male and female bone and cartilage cells in both animals and humans – differences that she believes probably affect a person’s risk for these diseases.

“The area of research that has intrigued me most is whether females possess special steroid hormone receptors or whether their receptors just operate differently,” says Boyan, the Price Gilbert, Jr. Chair in Tissue Engineering and a Georgia Research Alliance Eminent Scholar in Tissue Engineering.

Boyan’s ultimate goal is to understand why some people – women, in particular – have a greater propensity for osteoarthritis and osteoporosis.

A person’s gender is not the only risk factor for developing osteoporosis. Some people choose careers that induce osteoporosis. Such is the case for astronauts, who lose 1 to 2 percent of their bone mass for each month that they spend in space.

Hanjoong Jo, the Ada Lee and Pete Correll Professor in Biomedical Engineering, is investigating which genes may be responsible for the loss of bone mass in space or in paraplegic individuals. To do this, Jo conducts bone cell experiments in two simulators: a random positioning machine that rotates cells in a manner that tricks them into thinking they are in microgravity conditions, and a rotating wall vessel that models microgravity conditions by maintaining continuous free-fall.

Jo is also investigating ways to prevent bone loss or reverse it. He found that putting bone cells on a vibrator for a few minutes per day under microgravity conditions would retain bone mass, and he is currently studying the genes responsible for this turnaround. Jo’s work is supported by the National Institutes of Health.

Looking at the Big Picture

Professor Eberhard Voit uses mathematics to study the interactions between the components of biological systems and how these interactions give rise to the function and behavior of such systems, a field called computational systems biology.

Voit, who is the David D. Flanagan Chair in the Coulter Department and Georgia Research Alliance Eminent Scholar in Biological Systems, is studying Parkinson’s disease and schizophrenia. Symptoms of the two neurological disorders differ, but the hormone dopamine plays a role in both. Dopamine production is suppressed in individuals with Parkinson’s disease and increased in schizophrenic individuals.

Voit has teamed with Gary Miller, an associate professor in Emory’s Department of Environmental and Occupational Health, to develop a mathematical model of the dopamine network to better understand how genetic, environmental and pharmacological factors alter how dopamine functions in healthy neurotransmission and neurodegenerative diseases.

The researchers plan to use the model in conjunction with biological and clinical studies conducted at Emory University to screen novel therapeutics aimed at altering dopamine function and decreasing the symptoms of both disorders. This interdisciplinary research is being funded by the Woodruff Health Sciences Center’s Predictive Health Initiative at Emory University.

To expand systems biology research at Georgia Tech, Voit spearheaded the creation of Georgia Tech’s new Integrative BioSystems Institute (IBSI), a collaboration of the Colleges of Science, Engineering and Computing. He also serves as its inaugural director.

An active IBSI member is Melissa Kemp, a Coulter Department assistant professor and Georgia Cancer Coalition Distinguished Professor. She is using systems biology approaches to understand complex cancer pathways involved in drug-resistant acute lymphoblastic leukemia, a type of cancer of the white blood cells. Children with lymphoblastic leukemia exhibit a diverse response to chemotherapy, with about one-fourth of them relapsing with drug-resistant disease.

In collaboration with Harry Findley, an associate professor in Emory’s Department of Pediatrics, Kemp is studying the role of the protein NF-B in drug resistance of leukemia cells. NF-B activity is responsible for cell death decisions and increases when reactive oxygen species – such as oxygen ions, free radicals and peroxides – are present.

“Many chemotherapeutic agents produce reactive oxygen species as a side-product, which increases active NF-B levels. Unfortunately, drug-resistant cells appear to be better at eliminating these oxygen species,” explains Kemp.

With funding from Georgia Tech’s Health Systems Institute and the Georgia Cancer Coalition, Kemp is developing individualized computational models to identify key enzymes involved in regulating NF-B. With pediatric patient samples from Findley, she can test an individual’s enzyme levels to predict the likelihood of drug resistance.

Biomedical engineering has witnessed rapid expansion in the last decade. Advances in molecular biology, biophysics and nanotechnology are transforming the understanding of disease, and how it is diagnosed and treated. With all four buildings in the Biotechnology Complex now filled with researchers, Georgia Tech’s commitment to bioscience and engineering is clear, and the Coulter Department is leading the way.

Comments and conclusions expressed in this article are solely the responsibility of the faculty members making them and do not necessarily represent the official views of the National Institutes of Health or the National Science Foundation.

Public and Private: Creating the Coulter Department of Biomedical Engineering

Even before the joint Department of Biomedical Engineering at Georgia Tech and Emory University was created in 1997, the two institutions collaborated on biomedical research. The Emory-Georgia Tech Biomedical Technology Research Center, which established a seed grant program to stimulate research between the medical school at Emory and researchers at Georgia Tech, began cultivating cross-town partnerships in 1987.

But this $400,000-per-year seed grant program wasn’t enough for former Georgia Tech provost Michael Thomas and former executive vice president for health affairs at Emory University Michael Johns. They wanted more collaboration.

“When I joined Emory in 1996, I was surprised that Emory didn’t have a biomedical engineering department,” recalls Johns, who now serves as chancellor of Emory University. “When I realized Georgia Tech didn’t have one either, I thought it would be the perfect marriage of the faculty in the engineering school at Georgia Tech and the medical faculty at Emory.”

To discuss the possibility of a joint biomedical engineering department, Johns and Emory Dean of Medicine Thomas Lawley met with Thomas and Robert Nerem, a mechanical engineering professor at Georgia Tech and director of the Parker H. Petit Institute for Bioengineering and Bioscience, a research institute whose mission is to integrate engineering, information technology and the life sciences in biomedical research.

They formed an advisory committee of Georgia Tech and Emory faculty to develop a set of recommendations for an innovative and unique joint department of biomedical engineering. Leading the committee was Don Giddens, an aerospace engineering professor at Georgia Tech from 1968-1992 who returned from being dean of engineering at Johns Hopkins University to chair the new biomedical engineering department.

“Getting Don to return was absolutely key to the success of the department,” says Thomas. “You can’t have success without quality leadership and Don created an environment of trust, discovery, innovation and enthusiasm with his vision for the department.”

In 2000, The Whitaker Foundation awarded the biomedical engineering department a $16 million leadership-development award. Six million dollars of the grant was used to further develop the undergraduate and graduate programs, hire new faculty and support graduate student fellowships. The other $10 million helped construct the four-story, nearly 100,000-square-foot U.A. Whitaker Building at Georgia Tech, where most of the biomedical engineering faculty offices, laboratories and classrooms are located.

In 2001, the Wallace H. Coulter Foundation awarded a $25 million grant to the department. In recognition of this grant, the combined department is now known as the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University. Included within this grant were operating funds to purchase laboratory equipment and fund endowed chairs, and an $8 million endowment (which now totals $10 million) to provide ongoing funding for translational research.

After Giddens became dean of Georgia Tech’s College of Engineering in July 2002, Larry McIntire joined Georgia Tech as the new department chair. Under his leadership, the Coulter Department garnered almost $17 million in funding from the National Institutes of Health in 2007.

The department has grown to include 45 primary faculty members, 175 graduate students and more than 800 undergraduate students. In the “America’s Best Colleges 2008” edition of U.S. News & World Report, the undergraduate program ranked third and the doctoral program ranked second in the biomedical engineering specialty category.

Just one goal is still in the making: to have the biomedical engineering program ranked number one in the country.

Wallace H. Coulter: His Legacy is Accelerating Translational Biomedical Engineering Research

Biomedical engineering professors at Georgia Tech and Emory University are designing systems to detect Alzheimer’s disease earlier, improving the effectiveness of pacemakers and developing cardiovascular implants to increase the durability of heart valve repairs.

Translational research projects like these – which move science from the laboratory bench to the bedside – are possible because of a $25 million grant from the Wallace H. Coulter Foundation in 2001. The grant includes a unique $10 million endowment to provide ongoing funding for translational research.

“This grant was awarded because I believed in the vision and mission of [founding Coulter Department chair] Don Giddens and his strategy to lead the department to be the best in the nation,” says Sue Van, president of the Foundation. “I am delighted that Wallace’s legacy is helping to plant the seeds of the next generation of biomedical engineering applications.”

In recognition of the grant, the biomedical engineering department at Georgia Tech and Emory University was named for Coulter – an engineer, inventor, entrepreneur and visionary whose motto in life was “science serving humanity.” Coulter, who was a student at Georgia Tech in the early 1930s, invented the Coulter Principle, the reference method for counting and sizing microscopic particles suspended in a fluid.

Remembering laboratory technicians hunched over microscopes manually counting blood cells smeared on glass, he developed the Coulter Counter, an automated device that counts red blood cells. Today, 98 percent of complete blood count tests – the most commonly ordered diagnostic test worldwide – are performed on instruments using the Coulter Principle.

The translational research program captures the spirit of Coulter’s own life’s work because the program requires collaboration between a biomedical engineer and a clinician. The results of the program have been so promising with regard to patents issued, companies launched and follow-on capital raised that it has become the template for the Foundation’s national Translational Research Partnership Program.

Since 2001, the partnership between the Coulter department and the Foundation has continued to evolve, most recently with a global focus.

“Again I believed in the vision of [now College of Engineering dean] Don Giddens,” says Van. “He understands that Georgia Tech must continue to expand its reach globally with leading universities in order to succeed in the 21st century.”

In 2007, the Foundation donated $500,000 to establish a seed grant program between Peking University in Beijing, China, and the Coulter Department.

“Coulter fell in love with China when he worked there in the 1930s – it’s where he developed his international perspective, which led to a profound and lifelong fondness for Chinese art, culture and society,” says Van. “It’s a win-win for everybody.”