June 29, 2001
Volume XXXIV, No. 26




UTHSC mouse model center targets late-life diseases

Photo of Dr. Vijg Dr. Jan Vijg is the principal investigator on the federal grant for mouse model development.

$3.5 million grant supports research at Barshop Center

The National Institute for Environmental Health Sciences recently tapped five research centers to develop new mouse models of disease, including the growing center on aging at the Health Science Center.

UTHSC scientists will receive $3.5 million over the next five years under the grant, titled "Models for Human DNA Repair and Cell Cycle Variants in Aging and Environmental Disease." The new center is part of the Sam and Ann Barshop Center for Longevity and Aging Research, housed at UTHSC's South Texas Centers for Biology in Medicine in the Texas Research Park.

"We were peer-reviewed and selected as the best, together with four other centers," said Dr. Jan Vijg, professor of physiology. The others are The University of Washington at Seattle, The University of Texas M. D. Anderson Cancer Center, the Albert Einstein College of Medicine, Bronx, N.Y., and The University of Cincinnati.

Scientists at the national institute are combing the genes of hundreds of people for distinguishing mutations. These mutations may explain why some people are more vulnerable to environmental insults, such as exposure to chemicals, and why others are so long-lived. The San Antonio team seeks to develop mouse models with genetic makeup nearly identical to the profiled humans. The purpose is to study both the effects of mutations and the effects of gene replacement and therapy.

"This center in San Antonio is important because of our focus on late-life diseases," Dr. Vijg said. "Of the five centers, ours is the only one concentrating on these diseases. This continues the legacy of Dr. Edward Masoro, who was at the Health Science Center in the 1970s, '80s and '90s. San Antonio is well known for studies of the basic processes of aging."

DNA, our genetic blueprint, is under constant assault both from forces within the body and from the environment. Rescue genes continuously encode amazing "DNA repair" proteins to correct the damage. "The problem is that as we age, the repair function seems to decline and our DNA deteriorates," Dr. Vijg said. "The older we get, the more likely it seems that our DNA will be damaged. Slow gene deterioration increases the risk of various diseases, including cancer."

Fifteen scientists in Texas, California and abroad will collaborate on the San Antonio project. While the Health Science Center focuses on the broad process of late-life diseases, other centers will study specific disease mechanisms such as those inherent in development of Alzheimer's or Parkinson's diseases.

Dr. Vijg is the principal investigator on the federal grant. The co-principal investigator is Dutch scientist Dr. Harry van Steeg. Collaborators are Drs. Jan Hoeijmakers of The Netherlands and Arlan G. Richardson of the Health Science Center. Dr. Vijg formerly studied under Dr. Hoeijmakers, who heads one of the world's foremost groups on DNA repair. Other collaborators are from The University of California, Berkeley.

The new effort should lead to development of categories of gene defects — and later to gene-tailored therapies. "We will study the mice to look for effects of each mutation," Dr. Vijg said. "Some mutations can have profound effects and cause diseases such as cancer and neurodegenerative disorders; however, many of the more common human gene mutations can be expected to have more subtle effects."

The researcher expects to spend $100,000 over a period of one to two years to develop each mouse model, but he said the group is making "rapid progress" to speed up the process.

Of particular interest to the National Institute of Environmental Health Sciences, the San Antonio team hopes to discover how relatively common gene mutations in the human population can confer either increased or reduced risk for certain environmental diseases.

The Health Science Center currently attracts more research grants from the National Institute on Aging than any health science center in the country except Massachusetts General Hospital in Boston.

Dr. Vijg, who soon will have a joint appointment with the South Texas Veterans Health Care System, is especially excited about an upcoming human genetics program at the Barshop Center and other initiatives, including studies of aging in lower invertebrates. "The San Antonio aging research community is enormously expanding right now," he said. "Within a few years, this will be the number one center for aging research in the country and in the world."