BBS Faculty Member - Anna Greka

Anna Greka

Department of Medicine

Brigham and Women's Hospital
Harvard Institute of Medicine
4 Blackfan Circle, 5th Floor
Boston, MA 02115
Tel: 617-525-5939
Fax: 617-726-5669
Email: agreka@partners.org
Visit my lab page here.



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. Our work 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 showed that inhibition of TRPC5 channels protects the kidney filter. Using Trpc5 knockout mice, a small molecule inhibitor of TRPC5, calcium imaging in isolated kidney glomeruli, and live imagining of podocyte actin dynamics, we determined that loss of TRPC5 or its inhibition abrogates podocyte cytoskeletal remodeling. Thus, our work revealed that the Ca+2 permeable channel TRPC5 is an important determinant of the early events causing albuminuria, and TRPC5 inhibition is thus a novel therapeutic strategy for the prevention or treatment of proteinuric kidney diseases.

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.



Last Update: 7/18/2014



Publications

For a complete listing of publications click here.

 


 

Schaldecker T, Kim S, Tarabanis C, Tian D, Hakroush S, Castonguay P, Ahn W, Wallentin H, Heid H, Hopkins CR, Lindsley CW, Riccio A, BuvallL, Weins A, and Greka A. Inhibition of the TRPC5 ion channel protects the kidney filter. Journal of Clinical Investigation November 15, 2013.

Yu C, Fornoni A, Weins A, Hakroush S, Maiguel D, Sageshima J, Chen L, Ciancio G, Faridi MH, Behr D, Campbell KN, Chang JM, Chen HC, Oh J, Faul C, Arnaout MA, Fiorina P, Gupta V, Greka A, Burke G, and Mundel P. Abatacept in B7-1 Positive Proteinuric Kidney Disease.N Engl J Med. November 8, 2013, DOI: 10.1056/NEJMoa1304572

Greka, A. and Mundel, P. Cell biology and pathology of podocytes. Annual Reviews of Physiology, 74, 299-323, 2012.


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.

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.

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.



© 2013 by the President and Fellows of Harvard College