Photo by Rebecca Arrington

Biomedical engineers Thomas C. Skalak (seated) and Richard J. Price are part of the team investigating the growth of blood vessels and neural tissue and the development of blood vessels in the kidneys.

Researchers studying the complex process of tissue growth

HOW IS IT that genes tell cells what kinds of cells they are to become? And then how do those cells get together and organize themselves into coherent tissues?

A U.Va. team — jump-started with a $200,000 University seed grant that in turn led to a $3.6 million award from the National Institutes of Health — is taking aim at understanding some of these most basic principles of human physiology.

By Charlotte Crystal

Just as a New York City taxi driver reacts to constantly changing traffic-red lights, jaywalkers, speeding cars, parked trucks — the body’s cells interact with
a jumble of genes, proteins, cells and external stimuli as they race to create the blood vessels, nerves, tissue and organs that make up our bodies.

The international human genome project has identified the 30,000 or so genes that control the human body, but the scientific work of understanding what all the genes do and how they interact with various cells is just beginning.

A multidisciplinary group of researchers at the University is addressing three related aspects of that complex challenge, thanks to a $200,000 seed grant from the University’s Funding Excellence in Science and Technology (FEST) program and a subsequent grant of nearly $3.6 million from the National Institutes of Health.

The research team — which includes two biomedical engineers, Thomas C. Skalak and Richard J. Price; a molecular physiologist, Gary K. Owens; a developmental cell biologist, Douglas W. DeSimone; and a pediatrician and expert in kidney organogenesis (growing new kidney tissue) R. Ariel Gomez — will investigate the growth of blood vessels and neural tissue and the development of blood vessels in the kidneys, building on research already under way in each of the team members’ labs.

Photo by Jenny Gerow

The Biomedical and Medical Sciences Building on Lane Road, next to Jordan Hall, opened last month. The new space is home to the departments of biomedical engineering, pathology and comparative medicine, and the Cardiovascular Research Center. The 150,000-gross-square-foot building is a state-of-the-art space for teaching, labs and administrative support. The cost of the project was $42 million.

In particular, the researchers are studying how genes direct the assembly of individual cells into larger systems and the various interactions that take place along the way. Team members are exploring different aspects of the process from the smallest elements to the largest — from genes, to cells, to tissue.

The project draws on a number of cutting-edge techniques developed in U.Va. labs, including the use of computer analysis to predict the behavior of living systems, and the ability to watch microscopic activity in lab animals and construct computer models to mimic the complex processes, said Skalak, chair of the Department of Biomedical Engineering, a program co-sponsored by the School of Medicine and the School of Engineering and Applied Science.

The goal of this gene circuitry research is to advance the knowledge needed to harness the body’s natural ability to prevent disease, and eventually to grow replacement tissue for human transplantation, he said.

“We are extremely grateful for the visionary investment made by President John T. Casteen III and Provost Gene D. Block in this project,” Skalak said. “U.Va.’s financial support was instrumental in helping these researchers secure federal grants for this project and related research, representing a return on investment of more than 3,000 percent. Our experience confirms the wisdom of the FEST program and promises to pay tremendous scientific dividends in improved health for all.

“We also believe this project will help boost the University’s biomedical engineering program, currently ranked 14th [by U.S. News & World Report], into the top 10,” Skalak said.

The U.Va. research project has many potential applications to major public health concerns in the United States.

For example, coronary heart disease, the single largest cause of death in the U.S., according to the American Heart Association, claims more than 500,000 lives each year. While transplants can save the most severely affected patients, there aren’t enough hearts to go around. In 2000, the most recent year for which figures are available, only 2,198 heart transplants were performed.

Progress has been made through ongoing efforts to educate the public about the importance of a heart-healthy diet and regular exercise. There also have been recent developments in the use of mechanical hearts. But research that suggests ways to harness the body’s capabilities to prevent heart failure in the first place is not as far along, according to Skalak.

It is just this kind of preliminary — but promising — research the FEST program was designed to encourage when Casteen announced its creation two years ago. Founded on the recommendation of the Virginia2020 Science and Technology Commission and funded with an annual commitment of $1 million from the president’s office, the program’s goal is to encourage innovative, multidisciplinary research and strengthen centers of excellence at U.Va., while attracting major funding from outside sources.

FEST grants, which run from $10,000 to $500,000, are awarded on the basis of a project’s potential to solve a major scientific or technological problem, create intellectual property and have an international impact. So far, the program has awarded 14 grants for more than $1 million, with the next round of funding coming up later this year.

This gene circuitry project is believed to be the first to secure a large federal grant by building on FEST funding, as envisioned by the FEST program founders.

“The difficulty has been in choosing among a large number of significant research projects submitted by a broad array of talented University scientists,” said Block, who served as vice president for research and public service before assuming his curent post as vice president and provost. “We were glad to see that a national funding agency shared our assessment of the significance and promise of the multifaceted research being conducted at U.Va. We are certain the FEST program will act as a funding springboard for other projects in the future.”