$2.5 million grant supports research into potential pharmaceutical targets for treating vascular complications of diabetes
NEW YORK (May 21, 2007) -- A leading authority and pioneer in the pharmacology of the signaling molecule nitric oxide (NO), Weill Cornell Medical College scientist Dr. Steven S. Gross has been selected by the National Heart, Lung, and Blood Institute (NHLBI) to receive a 2007 National Institutes of Health (NIH) Method to Extend Research in Time (MERIT) Award, representing the fourth year the College has been selected for the prestigious honor.
This year's $2.5 million five-year research grant will provide long-term support for research aimed at furthering understanding of the NO-related trigger for vascular complications of diabetes and developing novel pharmaceutical approaches for ameliorating the condition.
Dr. Gross is professor of pharmacology, director of the mass spectrometry core facility and principal investigator on an NIH grant that supports the training of Ph.D. candidates in the Graduate School Program in Pharmacology at Weill Cornell Medical College.
"We are extremely grateful for the NIH's continued support for our translational research efforts," says Dr. Antonio M. Gotto Jr., the Stephen and Suzanne Weiss Dean of Weill Cornell Medical College. "Dr. Gross is highly deserving of this honor. His research has uncovered a wealth of information about the important role of nitric oxide in the body. This work, which has laid the groundwork for treatments of numerous disease conditions that have been attributed to nitric oxide excess or insufficiency, is currently focused on new approaches for one of the most painful complications of diabetes."
Beginning in the late 1980s, Dr. Gross and colleagues made several key discoveries about nitric oxide. Working with Dr. Roberto Levi and colleagues at Weill Cornell, 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.'"
What was previously thought to be a simple environmental toxin was discovered to be (1) produced by the cells of all mammals, including humans, and (2) a signaling molecule that plays a part in diverse and vital bodily functions such as fighting infections, communicating between nerve cells, determining the diameter of blood vessels, and the force of a heart's contraction. Dr. Gross' lab contributed to research that implicates dysfunctional NO signaling as a culprit in lethal cardiovascular conditions such as septic, cardiogenic and hemorrhagic shock; it may play a role in many other illnesses as well. Importantly, Dr. Gross' research has provided fundamental insights into ways of controlling NO synthesis, opening the door to potential new therapies.
"Congratulations to Dr. Gross whose focused work has furthered the field of pharmacology and may, in the future, lead to significant advances in the care of patients. Steve has done a tremendous job here, and his erudition is exemplary. I wish him continued success as he follows this promising avenue of research," says Dr. David P. Hajjar, the Frank H.T. Rhodes Distinguished Professor of Cardiovascular Biology and Genetics, dean of Weill Cornell Graduate School, and vice provost/executive vice dean for research at the Medical College.
"I want to thank the NIH for their long-term support for our work. For almost 20 years, my colleagues and I have worked to unlock the mysteries of nitric oxide. This new funding is vitally important as we continue this effort," says Dr. Gross. "We hope to further elucidate the role of nitric oxide as it mediates peripheral blood flow, and uncover potential targets for therapies aimed at patients with diabetes."
In 2006, Dr. Gross reported the first-ever method of combing through the body's tens of thousands of proteins to inventory sites of S-nitrosylation (S-NO), a protein associated with NO. The state-of-the-art mass spectrometry method, called SNO Site IDentification (SNOSID), represents a breakthrough for both basic science and drug research -- a tool that may significantly accelerate understanding of NO signaling.
Dr. Gross and other Weill Cornell scientists anticipate the benefits of new drugs that inhibit NO synthesis. A Phase III clinical trial, based on Weill Cornell technology and funded by the NIH, is testing whether such a drug can save the lives of patients with cardiogenic shock, an emergency condition that kills more than half of its victims and occurs in 8 percent to 10 percent of patients with severe heart attacks.
Over fifteen issued U.S. patents and foreign counterparts translate basic laboratory discoveries of Dr. Gross and colleagues into new strategies for the control of NO levels in patients. These include use of NO synthesis blockers to reverse hypotension (1989) and increase responsiveness to pressor drugs (1991, 1994); novel approaches to limit the availability of substrates for NO synthesis (1994, 1995, 1996); blocking the synthesis (1999, 2000, 2001) and use (1996) of tetrahydrobiopterin, an essential NO synthesis cofactor (2001); treatments based on discovery that NO synthase is a paraquat diaphorase (2001); pharmacotherapy for vascular dysfunction associated with deficient NO bioactivity (2004); and reversing or preventing premature vascular senescence (2005).
Other recent Weill Cornell faculty recipients of NIH MERIT awards include Dr. Frederick R. Maxfield, 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, for research promoting a greater understanding of the specific processes of inflammation and methods to control them (2005); and Dr. Aaron J. Marcus, for the development of a new treatment for occlusive vascular diseases such as stroke, coronary artery disease and peripheral vascular disease (2004).
Dr. Steven S. Gross
Dr. Gross has authored or co-authored more than 150 research publications, book chapters, review articles and books in the area of NO biology. He is an active member of NIH Study Sections and is a founder and board director of the Nitric Oxide Society, a group that organizes the major annual international meetings on the subject of NO and publishes a peer-reviewed scientific journal with novel reports on NO biology and chemistry. Dr. Gross received his Ph.D. in biomedical science from the Mount Sinai School of Medicine in New York City.
National Heart, Lung, and Blood Institute
The NHLBI is part of the National Institutes of Health, the federal government's primary agency for biomedical and behavioral research. NIH established the MERIT Award in 1986 to provide extended grant support to investigators whose research competence, productivity and scientific contributions are distinctly superior. NIH is a component of the U.S. Department of Health and Human Services.
Weill Cornell Medical College
Weill Cornell Medical College -- located in New York City -- is committed to excellence in research, teaching, patient care and the advancement of the art and science of medicine. Weill Cornell, which is a principal academic affiliate of NewYork-Presbyterian Hospital, offers an innovative curriculum that integrates the teaching of basic and clinical sciences, problem-based learning, office-based preceptorships, and primary care and doctoring courses. Physicians and scientists of Weill Cornell Medical College are engaged in cutting-edge research in such areas as stem cells, genetics and gene therapy, geriatrics, neuroscience, structural biology, pharmacology, cardiovascular medicine, AIDS, obesity, cancer and psychiatry -- and continue to delve ever deeper into the molecular basis of disease in an effort to unlock the mysteries behind the human body and the malfunctions that result in serious medical disorders. Weill Cornell Medical College is the birthplace of many medical advances -- from the development of the Pap test for cervical cancer to the synthesis of penicillin, the first successful embryo-biopsy pregnancy and birth in the U.S., and most recently, the world's first clinical trial for gene therapy for Parkinson's disease. Weill Cornell's Physician Organization includes 650 clinical faculty, who provide the highest quality of care to their patients. For more information, visit www.med.cornell.edu.