OHSU

Graduate Studies Faculty

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David M. Cohen, M.D.

Professor of Medicine and Cell and Developmental Biology
Chief, Nephrology Section, Portland VA Medical Center
Admin Unit: SOM-DOM Nephrology & Hypertension
Phone: 503-220-8262x56654
Lab Phone: 503-220-8262x51178
Office: Building 101/Portland VA Medical Center
Mail Code: PP262
Programs:
Cell & Developmental Biology
Program in Molecular & Cellular Biosciences
Research Interests:
human genetics, genetic association, genetics, polymorphism, cell volume regulation, osmoregulation, ion channel, hyponatremia, kinase, signal transduction, physiology
Preceptor Rotations
Dr. Cohen has not indicated availability for preceptor rotations at this time.
Faculty Mentorship
Dr. Cohen has not indicated availability as a mentor at this time.
Profile

Education:

  • B.S. – Pennsylvania State University, State College, PA 1984 (combined five-year BS/MD program with Jefferson Medical College)
  • M.D. – Jefferson Medical College of Thomas Jefferson University, Philadelphia, PA 1986

 

Residency:

  • Internal Medicine – University Hospital of Boston University School of Medicine, Boston, MA 1986 -1989

 

Fellowship:

  • Nephrology Research Fellow – Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 1989-1992
  • Clinical Nephrology Fellow – Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 1992-1993
  • Research Fellow (Genetics) – Howard Hughes Medical Institute and Brigham and Women’s Hospital, Boston, MA 1993-1995

 

Research Interests:

Our lab focus concerns the sensing and regulation of water balance at the molecular and cellular levels, and at the level of the intact organism including humans.  Experimentally, we emphasize the functional consequences of human genetic polymorphisms in transport proteins as they affect systemic water balance and glucose metabolism.

In humans, water intake occurs in response to thirst and a variety of social cues. Although fluid intake may vary by a factor of ten from day to day, or from person to person, plasma tonicity is regulated with exquisite precision. Brain sensors of plasma tonicity govern the release of the water-conserving hormone, vasopressin. This hormone acts on the kidney collecting ducts to up- or down-regulate water extraction and retention from the glomerular filtrate. The net result is a modulation of water conservation. The nature of the sensors of systemic tonicity remained elusive for many decades; however, recent data from our group and from many others suggests that members of the transient receptor potential family of ion channels serve this role in brain and kidney. Our interest is in the molecular basis for this sensing of systemic tonicity, and upon the physiological effectors of this system.

 

Representative Publications:

  • Zhao H, Tian W, Xu H, Cohen DM. Urea signaling to immediate-early gene transcription in renal medullary cells requires transactivation of the epidermal growth factor receptor.  Biochemical Journal.  370:479-487, 2003.
  • Xu H, Zhao H, Tian W, Tian W, Yoshida K, Roullet JB, Cohen DM. Regulation of a transient receptor potential (TRP) channel by tyrosine phosphorylation: Src family kinase-dependent tyrosine phosphorylation of TRPV4 on Tyr-253 mediates its response to hypotonic stress. J. Biol. Chem.278:11520-11527, 2003.
  • Tian W, Salanova W, Xu H, Lindsley JN, Oyama TT, Anderson S, Bachmann S, Cohen DM.  Renal expression of osmotically responsive cation channel TRPV4 is restricted to water-impermeant nephron segments. Am. J. Physiol. 287:F17-F24, 2004.
  • Tian W, Fu Y, Wang DH, Cohen DM.  Regulation of TRPV1 by a renally expressed rat TRPV1 splice variant.  Am J Physiol – Renal. 290:F117-26, 2006.
  • Xu H, Fu Y, Tian W, Cohen DM. Glycosylation of the osmoresponsive transient receptor potential channel TRPV4 on Asn-651 influences membrane trafficking. Am J Physiol – Renal. 290:F1103-9, 2006.
  • Fu Y, Subramanya A, Rozansky, D, Cohen DM.  WNK kinases influence TRPV4 channel function and localization.  Am J Physiol– Renal. 290:F1305-14, 2006.
  • Xu H, Tian W, Fu Y, Oyama TT, Anderson S, Cohen DM.  Functional effects of non-synonymous polymorphisms in the human TRPV1 gene. Am J PhysiolRenal. 293:F1865-76, 2007.
  • Fu Y, Tian W, Pratt EB, Dirling LD, Shyng SL, Meshul CK, and Cohen DM. Down-regulation of ZnT8 expression in INS-1 rat pancreatic beta cells reduces insulin content and glucose-inducible insulin secretion.  PLoS ONEMay 25; 4:e5679, 2009
  • Tian W, Fu Y, Garcia-Elias A, Fernández-Fernández JM, Vicente R, Kramer PL, Klein RF, Hitzemann R, Orwoll ES, Wilmot B, McWeeney S, Valverde MA, Cohen DM. A loss-of-function non-synonymous polymorphism in the osmoregulatory TRPV4 gene is associated with human hyponatremia.  Proc Natl Acad Sci USA. 106:14034-9, 2009.
  • Fu Y, Chen Z, Blakemore AIF, Orwoll E, and Cohen DM.  Absence of AVPR2copy-number variation in eunatremic and dysnatremic subjects in non-Hispanic Caucasian populations. Physiological Genomics. 40:121-7, 2010.