Rajan Sah, MD, PhD

Portrait
Assistant Professor of Internal Medicine - Cardiovascular Medicine
Assistant Professor of Molecular Physiology and Biophysics

Contact Information

Iowa City, IA 52242
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Education

PhD, University of Toronto, Canada
MD, University of Toronto, Canada

Resident, New York Presbyterian Hospital/Memorial Sloan-Kettering Cancer Center/Weill Cornell Medical Center, New York
Fellow, Cardiology, Brigham & Women's Hospital/Harvard Medical School, Boston
Fellow, Research, Howard Hughes Medical Institute Children's Hospital, Harvard Medical School, Boston

Research Summary

Obesity, diabetes and metabolic syndrome are major public health problems and significant risk factors for heart disease in the United States and world-wide. As a clinical cardiologist, I am faced with managing these conditions in patients on a regular basis. My lab is currently focused on studying ion channels as regulators of cellular metabolism in skeletal muscle, adipose tissue and myocardium. Specifically, my research interests focus on intracellular signaling of transient receptor potential channels (including TRPV3, TRPV4 and TRPM7), and the recently identified volume regulatory anion channel SWELL1 (LRRC8a) as they relate to obesity 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/cas9-mediated knockout) in cultured cells (mouse and human) and freshly isolated primary cells (adipocytes, skeletal muscle fibers, cardiomyocytes). Genetic loss-of-function (CRISPR/cas9-mediated and conventional) mouse models for these ion channels are also used to examine the contributions of these ion channels in vivo and in disease settings. Through a close collaboration with the bariatric surgery program we also have access to freshly isolated human adipocytes from obese and lean patients for acute electrophysiological experiments and long-term culture.

Publications

Sah, R., Mesirca, P., Van den Boogert, M., Rosen, J., Mably, J., Mangoni, M. & Clapham, D. (2013). Ion channel-kinase TRPM7 is required for maintaining cardiac automaticity. Proc Natl Acad Sci USA, 110(32), E3037-3046.

Sah, R., Mesirca, P., Mason, X., Gibson, W., Bates-Withers, C., Van den Boogert, M., Chaudhuri, D., Pu, W., Mangoni, M. & Clapham, D. (2013). Timing of myocardial trpm7 deletion during cardiogenesis variably disrupts adult ventricular function, conduction, and repolarization. Circulation, 128(2), 101-114.

Ye, L., Kleiner, S., Wu, J., Sah, R., Gupta, R., Banks, A., Sah, R., Cohen, P., Khandekar, M., Boström, P., Mepani, R., Laznik, D., Kamenecka, T., Song, X., Liedtke, W., Mootha, V., Puigserver, P., Griffin, P., Clapham, D. & Spiegelman, B. (2012). TRPV4 is a regulator of adipose oxidative metabolism, inflammation, and energy homeostasis. Cell, 151(1), 96-110.

Ramirez, R. J., Sah, R., Liu, J., Rose, R. A. & Backx, P. H. (2011). Intracellular [Na(+)] modulates synergy between Na(+)/Ca (2+) exchanger and L-type Ca (2+) current in cardiac excitation-contraction coupling during action potentials. Basic research in cardiology, 106(6), 967-77. PMID: 21779914.

Bates-Withers, C., Sah, R. & Clapham, D. E. (2011). TRPM7, the Mg(2+) inhibited channel and kinase. Advances in experimental medicine and biology, 704, 173-83. PMID: 21290295.

Sah, R., Bates-Withers, C., Jin, J. & Clapham, D. (2010). Cardiac-targeted Trpm7 Deletion Generate Phenotypes Through Perturbations In Myocardial Development. Circulation, 122, A13843.

Sah, R., Epstein, L. M. & Kwong, R. Y. (2007). Images in cardiovascular medicine. Intramural atrial hematoma after catheter ablation for atrial tachyarrhythmias. Circulation, 115(18), e446-7. PMID: 17485585.

Trivieri, M. G., Oudit, G. Y., Sah, R., Kerfant, B. G., Sun, H., Gramolini, A. O., Pan, Y., Wickenden, A. D., Croteau, W., Morreale de Escobar, G., Pekhletski, R., St Germain, D., Maclennan, D. H. & Backx, P. H. (2006). Cardiac-specific elevations in thyroid hormone enhance contractility and prevent pressure overload-induced cardiac dysfunction. Proceedings of the National Academy of Sciences of the United States of America, 103(15), 6043-8. PMID: 16595628.

Sah, R., Ramirez, R. J., Oudit, G. Y., Gidrewicz, D., Trivieri, M. G., Zobel, C. & Backx, P. H. (2003). Regulation of cardiac excitation-contraction coupling by action potential repolarization: role of the transient outward potassium current (I(to)). The Journal of physiology, 546(Pt 1), 5-18. PMID: 12509475.

Sah, R., Ramirez, R. J., Marash, D., Oudit, G. Y., Zobel, C. & Backx, P. H. (2003). Regulation of excitation-contraction coupling by transient outward current in normal and diseased myocardium. Journal of Physiology, 546(1), 41412.

Kaprielian, R., Sah, R., Nguyen, T., Wickenden, A. D. & Backx, P. H. (2002). Myocardial infarction in rat eliminates regional heterogeneity of AP profiles, I(to) K(+) currents, and [Ca(2+)](i) transients. American journal of physiology. Heart and circulatory physiology, 283(3), H1157-68. PMID: 12181147.

Sah, R., Ramirez, R. J. & Backx, P. H. (2002). Modulation of Ca(2+) release in cardiac myocytes by changes in repolarization rate: role of phase-1 action potential repolarization in excitation-contraction coupling. Circulation research, 90(2), 165-73. PMID: 11834709.

Sah, R., Oudit, G. Y., Nguyen, T. T., Lim, H. W., Wickenden, A. D., Wilson, G. J., Molkentin, J. D. & Backx, P. H. (2002). Inhibition of calcineurin and sarcolemmal Ca2+ influx protects cardiac morphology and ventricular function in K(v)4.2N transgenic mice. Circulation, 105(15), 1850-6. PMID: 11956130.

Crackower, M. A., Oudit, G. Y., Kozieradzki, I., Sarao, R., Sun, H., Sasaki, T., Hirsch, E., Suzuki, A., Shioi, T., Irie-Sasaki, J., Sah, R., Cheng, H. Y., Rybin, V. O., Lembo, G., Fratta, L., Oliveira-dos-Santos, A. J., Benovic, J. L., Kahn, C. R., Izumo, S., Steinberg, S. F., Wymann, M. P., Backx, P. H. & Penninger, J. M. (2002). Regulation of myocardial contractility and cell size by distinct PI3K-PTEN signaling pathways. Cell, 110(6), 737-49. PMID: 12297047.

Oudit, G. Y., Kassiri, Z., Sah, R., Ramirez, R. J., Zobel, C. & Backx, P. H. (2001). The molecular physiology of the cardiac transient outward potassium current (Ito) in normal and diseased myocardium. J Mol Cell Cardiol, 33, 851-72.

Sah, R., Ramirez, R. J., Kaprielian, R. & Backx, P. H. (2001). Alterations in action potential profile enhance excitation-contraction coupling in rat cardiac myocytes. The Journal of physiology, 533(Pt 1), 201-14. PMID: 11351028.

Wickenden, A. D., Lee, P., Sah, R., Fishman, G. I. & Backx, P. H. (1999). Targeted expression of a Kv4.2 dominant-negative Subunit in the mouse heart. Circ Res, 85, 1067-76.

Sah, R. L., Tsushima, R. G. & Backx, P. H. (1998). Effects of local anesthetics on Na+ channels containing the equine hyperkalemic periodic paralysis mutation. The American journal of physiology, 275(2 Pt 1), C389-400. PMID: 9688593.

Hanna, W. J., Tsushima, R. G., Sah, R., McCutcheon, L. J., Marban, E. & Backx, P. H. (1996). The equine periodic paralysis Na+ channel mutation alters molecular transitions between the open and inactivated states. The Journal of physiology, 497 ( Pt 2), 349-64. PMID: 8961180.