655 W Baltimore Street BRB 5-039
Education and Training
1999 - B.Pharmacy, Pharmacology, Panjab University, India
2002 - M.Pharmacy, Pharmacology, Panjab University, India
2009 - Ph.D./M.S. Pharmacology, Ohio State University
2014 - Postdoctoral fellow, University of Utah
2020 - Researcher, University of California San Francisco
The focus of our research is the molecular physiology of mitochondrial calcium signaling, and its role in human physiology and disease states. Using an interdisciplinary approach leveraging direct patch-clamp methods on intracellular organelles like mitochondria with cell biology and omics (genomics/proteomics/metabolomics) techniques, we aim to decipher the fundamental mechanisms that regulate mitochondrial membrane excitability and ion homeostasis, that in turn, affect cellular excitability and metabolic plasticity.
I completed my graduate studies under the supervision of Dr. Keli Hu at The Ohio State University, where I studied the metabolic regulation of both cardiac and vascular ATP-sensitive K+ channels. I subsequently trained with Dr. Michael Sanguinetti at the University of Utah, where I examined the molecular physiology of several cardiac K+ channels (hERG/hEAG and Slo2.1) and their modulation by small drug molecules. I then undertook training with Dr. Alexey Zaitsev in the same institute. In his lab I developed a whole heart model of VF/ischemia, and explored pathological mechanisms that lead to early electrical failure during sudden cardiac death.
In my recent work with Dr. Yuriy Kirichok at University of California, I developed a recombinant cell system with improved throughput and stable electrophysiological recordings of mitochondrial ion channels. Using this system, we performed the first comprehensive patch-clamp analysis of the calcium-dependent regulation of mitochondrial calcium uniporter (MCU) by EF-hand containing accessory subunits, MICU1‒3.
My lab aims to answer fundamental questions related to the role of mitochondrial calcium signaling in cellular bioenergetics, specifically how mitochondria take up and release Ca2+, how seemingly small alterations in mitochondrial calcium signaling affect cellular or tissue bioenergetics and create a substrate for complex disorders via interaction with other genes or homeostatic processes.
Mitochondrial biology, calcium and redox signaling, cardiovascular physiology, muscle physiology, ion channels, transporters, membrane biophysics, electrophysiology, confocal imaging, metabolic disorders (Heart failure).
Kumari A, Nguyen D; Garg V (2023). "Patch clamp technique to study mitochondrial membrane biophysics", Journal of General Physiology 155 (8): e202313347.
Fefelova N, Wongjaikam S, Pamarthi SH, Siri-Angkul N, Comollo T, Kumari A, Garg V, Ivessa A, Chattipakorn SC, Chattipakorn N, Gwathmey JK, Xie LH (2023) "Deficiency of mitochondrial calcium uniporter abrogates iron overload-induced cardiac dysfunction by reducing ferroptosis" Basic Research in Cardiology 118 (1): 21.
Garg V, Paranjpe I, Unsulangi T, Suzuki J, Milescu LS, Kirichok YK (2021) "The Mechanism of MICU-Dependent Gating of the Mitochondrial Calcium Uniporter”, eLife. Aug 31;10:e69312. PMID: 34463251
Garg V, Garg V, Shrestha R, Sanguinetti MC, Kamp TJ, Wu JC (2018) "Human Induced Pluripotent Stem Cell–Derived Cardiomyocytes as Models for Cardiac Channelopathies: A Primer for Non-Electrophysiologist", Circ Res. Jul 6; 123(2): 224-243. PMCID: PMC6136439
Garg V, Taylor T, Warren M, Venable P, Sciuto K, Shibayama J, Zaitsev A (2015) "β-Adrenergic Stimulation and Rapid Pacing Mutually Promote Heterogeneous Electrical Failure and Ventricular Fibrillation in the Globally Ischemic Heart", Am J Physiol Heart Circ Physiol. May 1; 308(9): H1155-70. PMCID: PMC4551128
Venable PW,* Sciuto KJ,* Warren M, Taylor TG, Garg V, Shibayama J, and Zaitsev AV (2015) “Mitochondrial depolarization and asystole in the globally ischemic rabbit heart: coordinated response to interventions affecting energy balance”, Am J Physiol Heart Circ Physiol. Mar 1;308(5):H485-99. PMCID: PMC4346765
Garg V, Stary-Weinzinger A, Sanguinetti MC (2013) “ICA-105574 Interacts with a Common Binding Site to Elicit Opposite Effects on Inactivation Gating of EAG and ERG Potassium Channels”, Molecular pharmacology 83 (4), 805-813. PMCID: PMC3608434
Garg V, Sachse FB, Sanguinetti MC (2012) “Tuning of EAG K+ channel inactivation: Molecular determinants of amplification by mutations and a small molecule”, The Journal of General Physiology 140 (3), 307-324. PMCID: PMC3434097
Garg V, Kirichok YY. (2019) "Patch-clamp analysis of the mitochondrial calcium uniporter", Methods Mol Biol. 1925: 75-86.
Garg V, Paranjpe I, Unsulangi T, Suzuki J, Milescu LS, and Kirichok YY. (2019) "Mechanism of mitochondrial calcium uniporter regulation". Circulation Research 125: A570
Garg V, Kirichok YY. (2019) "Patch-clamp analysis of the mitochondrial calcium uniporter". Methods Mol Biol. 1925: 75-86.
Garg V, Kirichok YY. (2016) "Keeping a lid on calcium uptake". Elife. 5. (commentary) Warren M, Sciuto KJ, Taylor TG, Garg V, Torres NS, Shibayama J, Spitzer KW, Zaitsev AV. (2017) "Blockade of CaMKII depresses conduction preferentially in the right ventricular outflow tract and promotes ischemic ventricular fibrillation in the rabbit heart." Am J Physiol Heart Circ Physiol. 312: H752-H767. PMCID: PMC4892888
Garg V, Gardner A, Garg V, Sanguinetti MC. (2013) "Structural basis of ion permeation gating in Slo2.1 K+ channels". J Gen Physiol. 142: 523-42. PMCID: PMC3813382
Taylor TG, Venable PW, Booth A, Garg V, Shibayama J, Zaitsev AV. (2013) "Does the combination of hyperkalemia and KATP activation determine excitation rate gradient and electrical failure in the globally ischemic fibrillating heart?" Am J Physiol Heart Circ Physiol. 305: H903-12. PMCID: PMC3761339
Saegusa N, Garg V, Spitzer KW. (2013) "Modulation of ventricular transient outward K+ current by acidosis and its effects on excitation-contraction coupling". Am J Physiol Heart Circ Physiol. 304: H1680-96. PMCID: PMC3680771
Garg V, Stary-Weinzinger A, Sanguinetti MC. (2013) "ICA-105574 interacts with a common binding site to elicit opposite effects on inactivation gating of EAG and ERG potassium channels". Mol Pharmacol. 83: 805-13. PMCID: PMC3608434
Garg V, Taylor TG, Venable PW, Sciuto KJ, Shibayama J, Zaitsev A. (2013) "Blockade of Na+-sensitive K+ channels alleviates frequency-dependent electrical failure in an ex-vivo model of VF-induced cardiac arrest". Circulation 128 (22 Supplement), A211
Garg V, Sanguinetti M. (2012) "Modulation of EAG Channel Inactivation by ICA105574". Biophysical Journal 102 (3), 132a
Garg V, Stary-Weinzinger A, Sachse F, Sanguinetti MC. (2011) "Molecular determinants for activation of human ether-á-go-go-related gene 1 potassium channels by 3-nitro-n-(4-phenoxyphenyl) benzamide". Mol Pharmacol. 80: 630-7. PMCID: PMC3187531
Garg V, Sachse F, Sanguinetti M. (2011) "Structural Basis of Action for a Novel hERG1 Channel Activator". Biophysical Journal 100 (3), 102a-103a
Dai L, Garg V, Sanguinetti MC. (2010) "Activation of Slo2.1 channels by niflumic acid". J Gen Physiol 135: 275-95. PMCID: PMC2828905
Zhang L, Chen CL, Kang PT, Garg V, Hu K, Green-Church KB, Chen YR. (2010) "Peroxynitrite-mediated oxidative modifications of complex II: relevance in myocardial infarction". Biochemistry. 49: 2529-39. PMCID: PMC3754874
Garg V, Sun W, Hu K. (2009) "Caveolin-3 negatively regulates recombinant cardiac KATP channels". Biochem Biophys Res Commun. 385: 472-7.
Garg V, Jiao J, Hu K. (2009) "Regulation of ATP-sensitive K+ channels by caveolin-enriched microdomains in cardiac myocytes". Cardiovasc Res. 82: 51-8.
Garg V, Hu K. (2009) "Association of ATP-sensitive K+ channels with adenosine A1 receptors". The FASEB Journal 23, 1000.13
Jiao J, Garg V, Yang B, Elton TS, Hu K. (2008) "Protein kinase C-ε induces caveolin-dependent internalization of vascular adenosine 5'-triphosphate-sensitive K+ channels". Hypertension. 52: 499-506.
Jiao JD*, Garg V*, Yang B, Hu K. (2008) "Novel functional role of heat shock protein 90 in ATP-sensitive K+ channel-mediated hypoxic preconditioning". Cardiovasc Res. 77: 126-33. *(equal contribution).
Garg V, Hu K. (2007) "Protein kinase C isoform-dependent modulation of ATP-sensitive K+ channels in mitochondrial inner membrane". Am J Physiol Heart Circ Physiol. 293: H322-32.
Jiao J, Garg V, Yang B, Hu K. (2007) "Protein Kinase C ε Inhibits vascular KATP channels by caveolae-dependent mechanism". Circulation 116 (16 Supplement), II_12
Singh A, Garg V, Gupta S, Kulkarni SK (2002) "Role of antioxidants in chronic fatigue syndrome in mice". Indian J Exp Biol 40: 1240-44.
June 2023-July 2027
National Institute of General Medical Sciences (R01)
"Molecular Physiology of Mitochondrial Calcium Uniporter (MCU)"