The NIH has approved a five-year extension of a major grant to Dr. Steven Gross, professor of pharmacology at Weill Cornell Medical College, to study vascular dysfunction associated with diabetes. This funding will continue through 2017.
Dr. Gross was selected by the National Heart, Lung and Blood Institute (NHLBI) in 2007 to receive a $2.5 million National Institutes of Health (NIH) Method to Extend Research in Time (MERIT) Award. Scientists do not apply for MERIT awards; instead, they are chosen by the NIH for grant extension based on a determination of "consistent outstanding contributions to biomedical science and to our Institute."
"The first few years were about validating our fundamental hypotheses, and now that we've done that, we are going to work on applying them," says Dr. Gross, who is also the director of the mass spectrometry core facility at Weill Cornell.
Dr. Gross is a leading authority and pioneer in mechanisms of signaling by the molecule nitric oxide (NO). Among its many physiological activities, nitric oxide is a vasodilator that's produced by the endothelial cells that line the blood vessels. A deficit of nitric oxide causes the vascular dysfunction associated with diabetes. Diabetics, with high levels of blood sugar, also have high levels of superoxide in their blood vessels, which consumes nitric oxide. This deficiency in NO in diabetics is thought to be a major reason for amputations, blindness, kidney failure and may potentially lead to death.
"We are working on developing chemicals that will react with the superoxide to release nitric oxide," Dr. Gross says. "The concept is to selectively deliver nitric oxide at the places in the vasculature where you have the greatest excess of superoxide — where nitric oxide is most deficient and needed." The goal of this new therapeutic strategy is to prevent or reverse the vascular complications of diabetes.
Beginning in the late 1980s, Dr. Gross and colleagues made several key discoveries about nitric oxide. Working with Dr. Roberto Levi, professor of pharmacology, and colleagues at Weill Cornell Medical College, Dr. Gross was a member of the first group to administer a selective inhibitor of NO synthesis to an animal.
"The astounding increase in blood pressure that ensued, later confirmed to occur also in healthy human subjects, immediately taught us that nitric oxide plays a fundamental role in keeping blood vessels open and blood pressure low," says Dr. Gross. "We now recognize that insufficient nitric oxide is the basis for high blood pressure (hypertension) in most patients that require treatment for this condition, and reciprocally, excess production of nitric oxide mediates the potentially lethal low blood pressure associated with multiple forms of 'shock.'"
Dr. Gross' initial MERIT Award, and the extension, add to the legacy of the NIH MERIT Award at Weill Cornell. Past faculty members to receive this prestigious honor include Dr. Frederick R. Maxfield, chairman of the Department of Biochemistry and the Vladimir Horowitz and Wanda Toscanini Horowitz Distinguished Professor of Neuroscience at Weill Cornell, for efforts to better understand the ways in which cell receptors, transporters, lipids and other key molecules move within and between cells (2006); Dr. William Muller, adjunct professor of pathology and laboratory medicine, for research promoting a greater understanding of the specific processes of inflammation and methods to control them (2005); and Dr. Aaron J. Marcus, professor of medicine, for the development of a new treatment for occlusive vascular diseases such as stroke, coronary artery disease and peripheral vascular disease (2004).