U.S. Department of Health and Human Services

Molecular Medicine Branch

Alan Neil Schechter, M.D., Chief

Laboratories

Molecular Biology and Genetics Section

Alan Neil Schechter, M.D.

The Molecular Biology and Genetics Section now focuses on studies of nitric oxide (NO) metabolism, its role in disease pathophysiology, and its potential therapeutic utility. Overall, the primary aims of this research are to show how erythrocytes and hemoglobin have major functions beyond oxygen transport and to understand how these are involved in the metabolic pathways of nitrate, nitrite, and NO. We have shown that reduction of nitrite ions by heme proteins, such as hemoglobin, is a major source of bioactive NO in the body. This raises the possibility that nitrite, or its precursor nitrate, might be used therapeutically in conditions where this function is effectively depleted. In particular, cell-free hemoglobin present in individuals with acute and chronic anemia may cause pathology by several mechanisms, including depletion of NO. Recent work has shown that NO is essential to the control of blood flow in the brain in response to various stimuli and that platelet reactivity is modulated by nitrite reduction to NO in the blood. This may explain differences between arterial and venous blood clotting and open up a new pharmacology.

Molecular Cell Biology Section

Constance Tom Noguchi, Ph.D.

The Molecular Cell Biology Section addresses non-erythroid effects of the hormone erythropoietin (Epo). Section scientists have shown that many neuronal cells produce Epo. The Epo-receptor signaling pathway contributes to neural protection, especially in response to hypoxia, and also protects against traumatic brain injury. Epo is necessary for the proliferation of neural progenitor cells and, in animal models, Epo facilitates myoblast transplantation and helps protect heart function. More recently, section members have shown that Epo protects against obesity and abnormal glucose metabolism in rodents fed a high-fat diet. A new area of research is the interaction of Epo with these pathways and the relevance of Epo to diabetes and its treatment.