We are using the tools of molecular biology, cell biology, advanced imaging techniques, patch clamp electrophysiology and animal models to study the role of TRP channels in health and disease.

Anna Greka, MD, PhD 
Assistant Professor of Medicine
149 13th Street
Charlestown, MA 02129
Phone: (617) 726-9363
Fax: (617) 726-5669
Email: greka.anna@mgh.harvard.edu

 

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Our laboratory is broadly interested in the biology of calcium signaling.  Thousands of calcium channels on the cell’s plasma membrane precisely control the timing and entry of calcium ions. Calcium permeates the membrane of virtually every cell to mediate vital processes such as contraction, vesicle secretion, gene transcription, and programmed cell death, to name a few.  We are particularly interested in the role of calcium in the regulation of the actin cytoskeleton. Aberrant calcium signaling leading to a disrupted cytoskeleton has been linked to neurologic disorders, heart disease, cancer, and kidney disease.  

Our current efforts are focused on Transient Receptor Potential channels (TRP) as regulators of actin dynamics and cell motility in glomerular podocytes, fibroblasts and neurons.  We recently uncovered TRPC5 and TRPC6 as the calcium influx pathways regulating the activity of the RhoGTPases Rac1 and RhoA, respectively.  

Our current efforts are also directed toward understanding the role of TRPC channels in proteinuric kidney disease.  We recently revealed that TRPC-mediated Rho GTPase signaling may cause podocyte damage, and TRPC channels may therefore provide a novel target for anti-proteinuric therapies in acquired, Angiotensin-associated proteinuric disease such as hypertensive and/or diabetic nephropathy.

We are using the tools of molecular biology, cell biology, advanced imaging techniques, patch clamp electrophysiology and animal models to study the role of TRP channels in health and disease.

References:

  1. Greka, A. and Mundel, P. Balancing calcium signals through TRPC5 and TRPC6 in podocytes. Journal of the American Society of Nephrology, 22: 1969-1980, 2011.
  2. Greka, A. and Mundel, P. Cell biology and pathology of podocytes. Annual Reviews of Physiology, 74, epub Nov4 2011.
  3. Tian D, Jacobo SMP, Billing D, Rozkalne A, Gage SD, Anagnostou T, Pavenstaedt H, Hsu HH, Schlondorff J, Ramos A, and Greka A.  Antagonistic Regulation of Actin Dynamics and Cell Motility by TRPC5 and TRPC6 Channels. Science Signaling. 2010. 3, ra77. This paper was featured on the Science website “Calcium Signals Both Stop and Go,” October 26, 2010.
  4. Rhee EP, Souza A, Farell L, Steele JRD, Pollak M, Thadhani R, Clish CB, Greka A, and Gerszten RE.  Metabolite Profiling Identifies Novel Markers of Uremia and the Hemodialysis Procedure. Journal of the American Society of Nephrology. 2010. 21(6):1041-1051.
  5. Bezzerides VJ, Ramsey IS, Kotecha SA, Greka A, and Clapham DE. Rapid vesicular translocation and insertion of TRP channels. Nature Cell Biology. 2004. 6(8): 709 - 720.
  6. Greka A, Navarro B, Oancea E, Duggan A, and Clapham DE. TRPC5 is a regulator of hippocampal neurite length and growth cone morphology. Nature Neuroscience. 2003. 6(8): 837 - 845.