Manu Ben-Johny, Ph.D.
Assistant Professor of Physiology & Cellular Biophysics
Quantitative physiology and molecular biophysics.
My research interest lies at the intersection of quantitative physiology and molecular biophysics with the goal of employing engineering principles to study and manipulate ion channel signaling complexes that are critical to neurological and cardiovascular function. Specifically, we seek to (1) elucidate the sophisticated spatiotemporal feedback regulatory mechanisms by which cytosolic signaling molecules and second messengers (e.g. Ca2+ ions) tune voltage-gated sodium (Na) and calcium (Ca) channels, (2) exploit such in depth understanding with emerging protein engineering methods to devise a next-generation optogenetic and synthetic modulatory toolkit that precisely tunes Na and Ca channel function, and (3) exploit these tools to both delineate the role of these channels in normal physiology and to clarify how channel misregulation underlies complex human diseases such as cardiac arrhythmias and neurological disorders. To do so, we utilize a variety of methods including state-of-the-art fluorescence microscopy, photouncaging, low-noise single channel and whole-cell electrophysiology, quantitative modeling, and molecular simulations.
Papa A, Kushner J, Hennessey JA, Katchman AN, Zakharov SI, Chen BX, Yang L, Lu R, Leong S, Diaz J, Liu G, Roybal D, Liao X, Del Rivero Morfin PJ, Colecraft HM, Pitt GS, Clarke O, Topkara V, Ben-Johny M, Marx SO. Adrenergic CaV1.2 Activation via Rad Phosphorylation Converges at α1C I-II Loop. Circ Res. 2021 Jan 8;128(1):76-88Yue, D.N., and Yue, D.T. (2016) Determining the stoichiometry of macromolecular complexes in live-cells. Nature Communications 7:13709.
Kschonsak M, Chua HC, Weidling C, Chakouri N, Noland CL, Schott K, Chang T, Tam C, Patel N, Arthur CP, Leitner A, Ben-Johny M, Ciferri C, Pless SA, Payandeh J. Structural architecture of the human NALCN channelosome. Nature. 2021 Dec 20
Kang PW, Chakouri N, Diaz J, Tomaselli GF, Yue DT, Ben-Johny M. Elementary mechanisms of calmodulin regulation of NaV1.5 producing divergent arrhythmogenic phenotypes. Proc Natl Acad Sci U S A. 2021 May 25;118(21)
Niu J, Dick IE, Yang W, Bamgboye MA, Yue DT, Tomaselli G, Inoue T, Ben-Johny M. Allosteric regulators selectively prevent Ca2+-feedback of CaV and NaV channels. Elife. 2018
Banerjee R, Yoder JB, Yue DT, Amzel LM, Tomaselli GF, Gabelli SB, Ben-Johny M. Bilobal architecture is a requirement for calmodulin signaling to CaV1.3 channels. Proc Natl Acad Sci U S A. 2018 Mar 27;115(13):E3026-E3035