Donald E. Kohan, M.D., Ph.D.
Professor of Medicine
Division of Nephrology
Adjunct Professor of Physiology
endothelin, nitric oxide, progstaglandins, collecting duct, aquaporin-2, Cre recombinase, cell-specific gene targeting, hypertension
Dr. Kohan's laboratory studies two major areas. The first area is understanding the role of collecting duct-derived endothelin and nitric oxide in regulating systemic blood pressure and renal sodium and water excretion in health and disease. They have pioneered cell-specific gene targeting in the kidney using the Cre-loxP system and have used this technique to knockout components of the endothelin system selectively in principal cells of the collecting duct. Collecting duct endothelin-1 knockout mice are hypertensive and have impaired ability to excrete a sodium or water load. They work closely with Dr. Raoul Nelson's laboratory in ongoing efforts to optimize cell specific knockout, including development of inducible knockouts (using Cre coupled to the ligand-binding domain of the estrogen receptor or the tetracycline transactivator) as well as improved integration site independent transgene expression (using BAC clones). Dr. Kohan also interacts with Dr. Jean-Marc Lalouel on the physiology of distal nephron-derived renin as well as Dr. John Hoidal on the interaction between endothelins, nitric oxide and reactive oxygen species, and with Dr. Lance Miller on endothelin regulation of the epithelial Na transporter. Lastly, the technique of cell-specific gene targeting has recently been adapted by Dr. Kohan's laboratory to developing a mouse model of polycystic kidney disease.
The other area of research in Dr. Kohan's laboratory involves understanding the mechanisms of cell injury in post-diarrheal hemolytic uremic syndrome. They have determined that renal tubular cells are highly susceptible to shigatoxin cytotoxicity, while endothelial cell sensitivity requires exposure to inflammatory cytokines. They have examined the molecular mechanisms controlling globotriaosylceramide (Gb3) expression (the major cognate shigatoxin receptor) and have determined that Gb3 synthase is a control site of Gb3 expression. They are now examining the signaling systems involved in controlling Gb3 synthase activity.
Last updated on 2010-01-14