Dr. Garner Haupert is an experienced and outstanding ion-transport physiologist and biochemist and an independent researcher with NIH support who continues his innovative work in the characterization of an endogenous hypothalamus-derived steroid inhibitor of the mammalian Na+, K+ -ATPase. This molecule is thought to be involved in the endogenous regulation of the Na+ pump and, in states of dyfunction, in the pathogenesis of certain forms of experimental and human essential hypertension. In collaboration with outstanding structural chemists, Haupert's hypothalamic inhibitory factor has been identified as an isomer of the plant cardiac glycoside, ouabain, although the precise stereochemistry remains to be resolved. Dr. Haupert's group has also recently isolated proteins in human plasma, which are felt to function as a reservoir and delivery system of the circulating form of the inhibitor. Dr. Haupert is now broadening his background and approach to bring this work into the molecular era. To this end, he is studying differential gene expression in brain and adrenal tissues from genetically hypertensive rats, which overproduce the inhibitor, using a combination of subtractive hybridization, cloning and microarray analysis. The goal of this work is to identify, clone and express genes potentially associated with the biosynthesis of the endogenous Na+, K+ -ATPase inhibitor. Dr. Haupert continues his clinical activities and teaching responsibilities at Massachusetts General Hospital (MGH) and Harvard Medical School as a member of MGH Renal Associates, and is a senior mentor in bedside teaching of medical residents and nephrology fellows.