Molecular Medicine Branch
Branch Sections and Chiefs
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Molecular Biology and Genetics Section
Alan Neil Schechter, M.D. -
Molecular Cell Biology Section
Constance Tom Noguchi, Ph.D.
Molecular Biology and Genetics Section
Alan Neil Schechter, M.D., Section Chief
The Molecular Biology and Genetics Section now largely focuses on studies of nitric oxide (NO) metabolism, its role in disease pathophysiology, and its potential therapeutic utility. This work evolved from our long-term studies of sickle cell disease pathophysiology and therapy, which continue in several collaborations. We have previously shown that erythrocytes and hemoglobin have major functions, beyond oxygen transport, in the metabolic pathways of nitrate, nitrite, and NO; in particular that reduction of nitrite and nitrate ions is a major source of bioactive NO in the body. This raises the possibility that these ions might be used therapeutically. Among other studies we have shown that platelet reactivity is modulated by nitrite reduction to NO in the blood and this may explain differences between arterial and venous blood clotting. We have also shown that skeletal muscle has very high levels of nitrate, which is reduced to NO during exercise, and can markedly increase blood flow and improve muscle function. This work is continuing largely in collaboration with exercise investigators at the University of Exeter, UK. Current work is also focusing on the fundamental NO pathways in the eye. We have found that lacrimal glands can secrete nitrate from the blood into the tears and are studying if this pathway accounts for much of the NO levels in the eye which affect intra-ocular fluid and retinal blood flow. All of these results have immediate nutritional and therapeutic implications.
Molecular Cell Biology Section
Constance Tom Noguchi, Ph.D., Section Chief
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.