Rajan Sah, M.D., Ph.D.

Associate Professor
Internal Medicine
Cardiology
Cell Biology and Physiology

Molecular Cell Biology Program
Biochemistry, Biophysics, and Structural Biology Program

  • rajan.sah@wustl.edu

  • Study the function of novel ion channels as they relate to growth and metabolism

Research Abstract:

My passion is to discover, develop and deliver better therapies for patients with cardiovascular disease. To this end I have directed my research efforts to identifying novel and innovative biological targets to open new, untested therapeutic avenues. My PhD training with Dr. Peter Backx and subsequent postdoctoral training with Dr. David Clapham in electrophysiology, ion channel signaling and calcium handling provides a unique mechanistic perspective into traditionally "non-electrical" diseases such as obesity and diabetes - diseases that ultimately culminate in heart disease and a huge burden of disability. Accordingly, since starting my independent research program, a major goal of my laboratory is to study the function of novel ion channels; specifically TRP channels (including TRPV3, TRPV4 and TRPM7), and the recently identified volume regulatory anion channel SWELL1 (LRRC8a) as they relate to growth and metabolism. To do this we combine cellular electrophysiology, calcium imaging (GCaMP6) and novel genetic techniques (including transient and stable lenti/AAV-shRNA-mediated knockdown and CRISPR-mediated knockout) in cultured cells (mouse and human) and freshly isolated, primary adipocytes, pancreatic β-cells, hepatocytes, skeletal myocytes, and endothelium. Genetic loss-of-function (CRISPR-mediated and conventional) mouse models for these ion channels are also used to examine their functions in vivo and in disease settings. By taking a "wideangle" view of ion channel signaling in biology, my laboratory has established several new independent research directions (in part through collaborative relationships) that emanates from our findings and leverages unique molecular tools and skill sets established in our laboratory.

Selected Publications:

1. Zhang Y, Xie L, Gunasekar S, Tong D, Mishra A, Gibson W, Wang C, Fidler T, Marthaler B, Klingelhutz A, Abel E.D, Smith J, Samuel I, Cao L, and Sah R. SWELL1 is a regulator of adipocyte size, insulin signaling and glucose homeostasis Nat Cell Biol. 2017 Apr 24. doi: 10.1038/ncb3514. [Epub ahead of print] PMID: 28436964

2. Kang C, Gunasekar S.K., Mishra A, Xie L, Zhang Y, Pai S, Gao Y, Norris A.W., Stephens S.B, Sah R., SWELL1 is a glucose sensor required for beta-cell excitability and systemic glycaemia. Nat Commun. 2018 Jan 25;9(1):367. doi: 10.1038/s41467-017-02664-0. PMID: 29371604.

3. Menegaz D*, Hagan DW*, Almaca J, Cianciaruso C, Rodriguez-Diaz R, Molina J, Becker MW, Dolan RM, Schwalie PC, Nano R, Lebreton F, Kang C, Sah R, Gaisano HY, Berggren P-O, Baekkeskov S**, Caicedo A**, and Phelps EA**. Mechanism and effects of pulsatile GABA secretion from cytosolic pools in the human beta cell. Nature Metabolism. 2019

4. Gunasekar, S.K., Xie, L., Sah, R. SWELL signaling in adipocytes: can fat "feel" fat? Adipocyte 2019 Dec;8(1):223-228. PMID: 31112068

5. Abiria S.A., Krapivinsky G., Sah R, Santa-Cruz A.G, Chaudhuri D., Zhang J., Adstamongkonkul P., DeCaen PG, Clapham D.E. TRPM7 Senses Oxidative Stress to Release Zn2+ from Unique Intracellular Vesicles Proc Natl Acad Sci U S A. 2017 Jul 25;114(30):E6079-E6088. pii: 201707380. doi: 10.1073/pnas.1707380114. PMID: 28696294

Last Updated: 2/14/2020 12:29:51 PM

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