The University Record, October 25, 1999

Four faculty members elected to Institute of Medicine

By Kara Gavin
Health System Public Relations

Four U-M medical researchers have been named to the Institute of Medicine, an extraordinarily large number to be elected from one institution in a single year.

David Ginsburg, Julian T. Hoff, James S. House and Michael A. Marletta join approximately 20 current and former U-M faculty in the 588-member national body, which named 55 new members earlier this week. Only Harvard University had more faculty than U-M elected this year.

Election to the Institute, the medical arm of the National Academy of Sciences, is an honor reserved for those who have made major contributions to health and medicine or related fields. One-fourth of the members are from fields outside the traditional health professions.

Institute members volunteer their time as members of committees devoted to studies on a broad range of health policy issues. Recent studies have focused on the future of the smallpox virus, the current state of cancer care, the medical use of marijuana, and donor organ procurement and transplantation.

David Ginsburg is the Warner-Lambert/Parke Davis Professor of Medicine, chief of the Division of Molecular Medicine and Genetics and professor of human genetics. He also is a Howard Hughes Medical Institute investigator.

Ginsburg has been cited as a leader in the effort to find the molecular genetic basis of human bleeding and clotting disorders. Notably, he has focused on the von Willebrand factor, or VWF, a protein central to the body’s blood coagulation system. Nearly 1 percent of the general population may have an inherited bleeding disorder caused by abnormal VWF. Ginsburg’s work began with the cloning of the VWF gene and now includes studies of how mutations in this gene lead to bleeding, and how mutations in other genes may also regulate VWF levels in blood.

Ginsburg and his team also research how blood clots are dissolved, and how abnormalities in this process contribute to human diseases including heart attack and stroke. His studies identifying the cause of another inherited bleeding condition have revealed important new information about how many proteins, including clotting factors, are transported within and out of cells.

Julian T. Hoff is head of the Neurosurgery Section and the Richard C. Schneider Professor of Neurosurgery. He also heads the Neurosurgery Training Program, one of the most sought-after neurosurgery residencies in the nation.

His Institute nomination calls Hoff a “triple threat” neurosurgery educator who combines clinical practice, teaching and research in a way that has brought him to national prominence and enabled him to influence the future of surgery. A clinical specialist in acoustic tumors, cervical spine surgery and brain tumors, Hoff also has conducted laboratory research on cerebral edema and intracerebral hemorrhage funded by the National Institutes of Health (NIH) for 25 years. He has received two NIH neuroscience awards.

His leadership activities in neurosurgery education include terms on the Residency Review Committee for Neurosurgery, as chair of the American Board of Neurological Surgery, and as chair of task forces on neurosurgery resident education and fellowship. A past president of the American Association of Neurological Surgeons and of the American Academy of Neurological Surgeons, he is president-elect of the Society of Neurological Surgeons, the principal society for neurosurgery educators, and second vice president in the American College of Surgeons.

James S. House, is director of the Survey Research Center (SRC) at the Institute for Social Research, professor of sociology, a research scientist in epidemiology and a faculty associate at the Institute of Gerontology.

House specializes in the role of social support and occupational stress in disease process and outcome. He was one of the first researchers to systematically study the role of social relationships and supports in health and illness through large and scientifically rigorous health studies. He showed that the influence of a lack of social relationships on mortality was comparable in impact to the effects of smoking. He also was one of the first to understand the importance of occupational stresses, and wrote Work Stress and Social Support, a book that helped to define important new areas of research.

Over the last decade, House has been studying through a national longitudinal survey the nature and explanation of socioeconomic disparities in the nature of health and the way health changes with age. His results suggest that differential exposure to psychosocial and behavioral risk factors for health across socioeconomic strata are probably more important for explaining those socioeconomic differences than differential access to medical care. His work as SRC director has included conducting and supporting national studies on health and aging. He is a member of the American Academy of Arts and Sciences and has been a Guggenheim Fellow.

Michael A. Marletta, is the John G. Searle Professor of Medicinal Chemistry and a professor of biological chemistry, as well as a Howard Hughes Medical Institute investigator. He also is chair of the Biological Sciences Scholars Program.

Marletta’s initial research on the biochemistry of nitrogen-containing compounds in the body has led to important knowledge about how cells send signals to one another, and has additional implications in toxicology. Specifically, his work on determining the biochemical precursor to nitrates and nitrites led to the discovery of a previously unknown metabolic pathway that produced the potent toxin nitrous oxide (NO). These novel findings provided the basis for other researchers’ work on NO and Marletta’s analysis of the enzyme and chemical mechanism that result in NO formation in humans and other animals.

NO has been found to be an important signaling molecule in the body, but it was a mysterious one until Marletta and his colleagues solved the riddle of how it sends signals from one cell to another even though its chemical reactivity with oxygen should cause it to decompose rapidly, preventing its function as a signaling agent. His studies also have shown how NO is able to signal without killing the cells that produce it. His work on the cellular receptor that captures NO molecules and keeps them from reacting with oxygen is important to the ongoing understanding of NO’s role in intercellular communication. These discoveries have led to NO’s clinical use in treating pulmonary hypertension and have led to potential treatments for stroke, colitis and toxic shock syndrome.