): The current era of scientific research is marked by an increasing interest in nutrition and metabolism, as it relates to HIV disease. This interest relates not only to the pathogenesis and clinical implications of obesity, but to role played by adipocytes and adipocyte signaling in modulating hormonal and higher cortical functions in such patients. Critical insights regarding the role of nutrient trafficking in the maintenance of glucose homeostasis, the pathophysiology and molecular basis of atherosclerosis, the profound consequences of abnormal nutrition, and the role of altered nutrition in reproduction and bone development have recently been made using HIV disease as a disease model. Furthermore, nutrition has become a major public health issue in the HIV population, with important effects on cardiovascular disease. Unfortunately, despite the increasing interest in nutrition and metabolism research, there are few established training programs for such research in patients with HIV disease and similar disorders of under and overnutrition. With the development of ever more powerful, but complex tools to study nutrient trafficking (PET and NMR), the genetic basis of diseases (genomics), and targeted treatment strategies (gene therapy), there is an acute need for sophisticated training in nutrition and metabolism, not covered under the rubric of existing programs. The purpose of this new training grant proposal is to train highly qualified M.D.'s and Ph.D's in the sophisticated techniques of clinical and translational nutrition research in the area of HIV disease, utilizing a well established group of mentors at Harvard Medical School, coordinated through the Harvard Division of Nutrition and MGH Program in Nutritional Metabolism. Application of clinical and basic investigation (e.g. nutrient signaling in the brain, the molecular mechanisms of fat redistribution, and the role of tissue specific GLUT-4 receptors) will be emphasized. Furthermore, the program offers opportunities for state of the art epidemiologic research into the public health consequences of obesity and malnutrition in HIV patients. The Faculty at the Harvard Division of Nutrition and the affiliated Hospitals and Schools (MGH, Brigham and Women's, Beth Israel Deaconess Medical Center, Children's Hospital, and the Harvard School of Public Health) are performing novel nutrition-related research and constitute a unique resource for training in nutrition and metabolism related directly to HIV and indirectly, via similar models of altered nutrient trafficking and metabolism. The established training record of the program faculty, broad research and educational opportunities in the Division and affiliated Programs, and rigorous training structure will contribute toward the stated goals of the proposal to train a new generation of investigators in nutrition and metabolism research related to HIV disease.
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