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Donald E. Kohan, M.D., Ph.D.

Professor of Medicine
Chief, Division of Nephrology
Director, Nephrology Training Program
Assistant Dean, Graduate Medical Education

donald.kohan@hsc.utah.edu

Phone: 801-581-6709

Fax: 801-581-4343

Office:

University of Utah Health Sciences Center

30 North 1900 East

Room 4R312

School of Medicine

Salt Lake City, UT 84132-2412

Research Interests

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 have 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. 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.

Recent Publications

Ergonal Z, Hughes AK, Kohan DE: Stx-1 induces apoptosis of human brain microvascular endothelial cells. J Infect Dis 187:154-158, 2003.

Ergonul Z, Clayton F, Fogo A, Kohan DE: Shigatoxin-1 binding and receptor expression in human kidneys do not change with age. Ped Nephrol 18:246-253, 2003.

Stricklett PK, Taylor D, Nelson RD, Kohan DE: Thick ascending limb-specific expression of Cre recombinase. Am J Physiol 285:F33-F39, 2003.

Ahn D, Ge Y, Stricklett PK, Gill P, Taylor D, Hughes AK, Yanagisawa M, Miller L, Nelson RD, Kohan DE: Collecting duct-specific knockout of endothelin-1 causes hypertension and sodium retention. J Clin Invest 114:504-511, 2004.

Stricklett PK, Hughes AK, Kohan DE: p38 MAP kinase inhibition ameliorates cytokine upregulated shigatoxin-1 toxicity in human brain microvascular endothelial cells. J Infect Dis 191:461-471, 2005.

Ge Y, Ahn D, Stricklett PK, Hughes AK, Yanagisawa M, Verbalis JG, Kohan DE. Collecting duct-specific knockout of endothelin-1 alters vasopressin regulation of urine osmolality. Am J Physiol 288:F912-F920, 2005.

Zhang H, Zhang A, Kohan DE, Gonzalez FJ, Nelson RD, Ye W, Yang T. Collecting duct-specific deletion of PPARgamma blocks thiazolidinedione-induced fluid retention. Proc Natl Acad Sci 102:9406-9411, 2005.

Guan Y, Hao R, Cha DR, Rao R, Lu W, Kohan DE, Magnuson M, Redha R, Zhang Y, Breyer MD. Thiazolidinediones expand body fluid volume by activating PPARgamma stimulation of ENaC-mediated renal salt absorption. Nature Medicine 11:861-866, 2005.

Ge Y, Stricklett PK, Hughes AK, Yang T, Yanagisawa M, Kohan DE. Collecting duct-specific knockout of the endothelin A receptor alters renal vasopressin responsiveness, but not sodium excretion or blood pressure. Am J Physiol 289:F692-F698, 2005.

Yang T, Zhang A, Honeggar M, Kohan DE, Mizel D, Sanders K, Hoidal JR, Briggs JP, Schnermann JB. Hypertonic induction of COX-2 in collecting duct cells by reactive oxygen species of mitochondrial origin. J Biol Chem 280:34966-34973, 2005.

Hughes AK, Stricklett PK, Strait KA, Kohan DE. Endothelin-1 stimulates NO production and inhibits cAMP accumulation in rat inner medullary collecting duct through independent pathways. Am J Physiol 290:F1315-F1319, 2006.

Ge Y, Bagnall A, Stricklett PK, Strait K, Webb D, Kotelevtsev Y, Kohan DE. Collecting duct-specific knockout of the endothelin B receptor causes hypertension and sodium retention. Am J Physiol 291:F1274-F1280, 2006.

Kohan DE: The renal medullary endothelin system in control of sodium and water excretion and systemic blood pressure. Current Opinion Nephrol Hypertens 15:34-40, 2006

Battistini B, Berthiaume N, Kelland NF, Webb DJ, Kohan DE: Profile of past and current clinical trials involving endothelin receptor antagonists: the novel "-sentan" class of drug. Exp Biol Med 231:653-695, 2006.

Strait KC, Stricklett PK, Kohan DE. Calcium regulation of endothelin-1 synthesis by inner medullary collecting duct. Am J Physiol 293:F601-F606, 2007.

Ge Y, Strait KA, Stricklett PK, Yang T, Kohan DE. Role of prostaglandins in collecting duct-derived endothelin-1 regulation of blood pressure and water excretion. Am J Physiol 293:F1805-F1810, 2007