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. He is currently the Interim head of the Divison of Nephrology.
B.S. – Pennsylvania State University, State College, PA 1984
M.D. – Jefferson Medical College of Thomas Jefferson University,
Internal Medicine – University Hospital of Boston University
School of Medicine, Boston, MA 1987-1989
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
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.
Renovascular disease, vasculitis, glomerulonephritis, disorders of
- 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,
- 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,
- 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,
- 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