Dr. Nadler, who also is professor and chair of the Department of Internal Medicine, is leading a team of scientists on the research. Also from EVMS are Anca D. Dobrian, PhD, assistant professor of physiological sciences and co-investigator on the grant, and Elena Galkina, PhD, assistant professor of microbiology and molecular cell biology. The EVMS team is collaborating with other well-known scientists in the field, including Alan Chait, MD, from the University of Washington, and Mark Kaplan, PhD, at Indiana University.
The team already has strong evidence to demonstrate that by controlling STAT-4, they can prevent long-term inflammation and the diseases that often follow.
Preliminary studies over the last two years show that when certain mice are fed a high-fat diet, they develop insulin resistance (a precursor to diabetes) and atherosclerosis (hardening of the arteries that is a hallmark of heart disease). But when scientists eliminate the STAT-4 gene, the mice do not develop disease and otherwise appear normal.
"You can't take out the gene in people, but you can develop drugs that work the same way," Dr. Nadler says. "We're not preventing obesity. That has to be a lifestyle change. But what we are able to do is help prevent some of the damaging effects."
The team will test their theory that the fat around the blood vessels can act as a reservoir of inflammation, feeding the vessel wall with inflammatory cells and leading to the development of vascular disease such as atherosclerosis.
"We have preliminary evidence showing that excess visceral fat can increase inflammation in the fat surrounding the blood vessels," Dr. Dobrian says. "The cross-talk between visceral fat, vascular fat and blood vessels is an exciting, novel concept that may explain better the complex relationship between obesity, diabetes and heart disease."
The researchers will use mice and
|Contact: Doug Gardner|
Eastern Virginia Medical School