Dr. Cohen joined the OHSU Nephrology staff in 1995. His clinical interests include renovascular disease, vasculitis, and glomerulonephritis. Dr. Cohen’s research interests center around the biochemical and molecular mechanisms through which kidney-specific stressors such as urea and hypo- and hypertonicity activate signaling pathways and regulate gene expression. Dr. Cohen is the Chief of Nephrology at the VA Medical Center.

Degrees:

B.S. – Pennsylvania State University, State College, PA 1984
M.D. – Jefferson Medical College of Thomas Jefferson University, Philadelphi

Residency:

Internal Medicine – University Hospital of Boston University School of Medicine, Boston, MA 1987-1989

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 Interest:

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.

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.

Osmoregulation is the process through which cell volume is maintained in the face of osmotic challenges. When a cell shrinks in response to a hypertonic milieu (through osmotic efflux of water), chemical and physical stimuli within the cell activate a coordinated protective response. The stressed cell imports ions to increase osmotic pressure and favor re-entry of water molecules. It also manufactures osmotically active organic solutes, and produces chaperone proteins to help offset the protein-denaturing effect of the increased intracellular ion concentration. Although this adaptive response is clearly important for single-celled organisms, it is just as vital for metazoans. In mammals, urine is concentrated as it traverses the hypertonic kidney medulla and papilla. Resident cells of this tissue survive extraordinarily high solute concentrations. Our group has explored the role of chaperones and the unique role of urea in helping these kidney epithelial cells adapt to rapidly fluctuating osmotic challenges.

Clinical Interest:

Renovascular disease, vasculitis, glomerulonephritis, disorders of water metabolism

Representative Publications:

• Zhao H, Tian W, Cohen DM. Rottlerin inhibits tonicity-dependent expression and action of the tonicity enhancer binding protein (TonEBP) in a PKC-delta-independent fashion. Am. J. Physiol. 282:F710-F717, 2002.
• Tian W, Cohen DM. Urea stress is more akin to EGF exposure than to hypertonic stress in renal medullary cells. Am. J. Physiol. 283:F388-F398, 2002.
• Komers R, Tian W, Lindsley JN, Oyama TT, Cohen DM, Anderson S. Effects of cyclooxygenase-2 (COX-2) inhibition on plasma and renal renin in diabetes. J. Lab. Clin. Med. 140:351-357, 2002.
• 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.
• Zhao H, Tian W, Tai C, Cohen DM. Hypertonic induction of COX-2 expression in renal medullary epithelial cells requires transactivation of the EGF receptor. Am. J. Physiol. In Press