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Dipayan Chaudhuri

Associate Professor of Internal Medicine and
Adjunct Associate Professor of Biochemistry and of Biomedical Engineering

Mitochondria, Heart Failure, ion Channels, Calcium Channels, Mitochondrial Diseases, Voltage-Clamp Electrophysiology, Metabolism, Calcium Imaging, Mitochondrial Calcium Uniporter

Chaudhuri

 

Molecular Biology Program

Biological Chemistry Program

Education

B.A. Cornell University

M.D., Ph.D. Johns Hopkins University School of Medicine

 

Research

We study how cardiac metabolism is altered in heart failure. As contractile function declines following cardiac injury, a well-documented rewiring of metabolism takes place, including a shift towards glycolysis, alterations in mitochondrial metabolism, and an increased tendency towards cardiomyocyte injury. Such rewiring leads to a global decline in ATP synthesis by the end stages of heart failure, when the only therapeutic options are heart transplant or lifelong mechanical support, and the severity of this decline presages mortality. In studying heart failure, we focus on calcium signaling, since this molecule is critical for cardiac contraction, rhythm, and metabolism. In fact, calcium entering the mitochondria potently stimulates ATP synthesis. We hope to define the molecular pathways that control mitochondrial calcium signaling and investigate if pharmacological modulation of these pathways can ultimately prove beneficial in heart failure.

Our current research focuses on two areas:

  1. Calcium regulation in mitochondrial cardiomyopathies: Mutations affecting mitochondrial function are among the most common forms of inborn errors of metabolism, primarily affecting infants and children. When such mitochondrial dysfunction leads to cardiac involvement, termed the mitochondrial cardiomyopathies, mortality rates increase threefold. In studying animal and cell models of these diseases, we have found that mitochondrial calcium levels are increased and are currently investigating (a) how such regulation occurs, and (b) how such changes affect cardiac function.
  1. Biophysics of mitochondrial ion channels: Because of their intracellular location, direct assessment of mitochondrial ion channels via classical electrophysiological techniques has been limited. We have overcome this barrier by studying mitoplasts, which are purified mitochondria stripped of their outer membranes. Such mitoplasts can be interrogated via voltage-clamping to allow measurement of ionic currents. Our laboratory is one of the few capable of performing this challenging technique. We use this technique to characterize the behavior of mitochondrial ion channels, including the mitochondrial calcium uniporter, the main portal for calcium entry into the mitochondrial matrix.

For these studies, we have expertise in a range of traditional and novel techniques in mitochondrial biology and calcium signaling, and are happy to share this expertise with our colleagues who are interested in detailed analyses of mitochondrial function or calcium kinetics.

References (Selected Publications)

  1. Ajanel A, Andrianova I, Kowalczyk M, Menéndez Pérez J, Bhatt SR, Portier I, Boone T, Ballard-Kordeliski A, Kosaka Y, Chaudhuri D, Paul DS, Bergmeier W, Denorme F, Campbell RA. Mitochondrial Calcium Uniporter Regulates ITAM-Dependent Platelet Activation. Circ Res. 2025 Jul 1;. doi: 10.1161/CIRCRESAHA.125.326443. [Epub ahead of print] PubMed PMID: 40590119; PubMed Central PMCID: PMC12258074.
  2. Rai NK, Eberhardt DR, Balynas AM, MacEwen MJS, Bratt AR, Sancak Y, Chaudhuri D. Mechanism of MCUB-Dependent Inhibition of Mitochondrial Calcium Uptake. J Cell Physiol. 2025 Apr;240(4):e70033. doi: 10.1002/jcp.70033. PubMed PMID: 40227803; PubMed Central PMCID: PMC11996009.
  3. Balderas E, Lee SHJ, Rai NK, Mollinedo DM, Duron HE, Chaudhuri D. Mitochondrial Calcium Regulation of Cardiac Metabolism in Health and Disease. Physiology (Bethesda). 2024 Sep 1;39(5):0. doi: 10.1152/physiol.00014.2024. Epub 2024 May 7. Review. PubMed PMID: 38713090; PubMed Central PMCID: PMC11460536.
  4. AI is a viable alternative to high throughput screening: a 318-target study. Sci Rep. 2024 Apr 2;14(1):7526. doi: 10.1038/s41598-024-54655-z. PubMed PMID: 38565852; PubMed Central PMCID: PMC10987645.
  5. Eberhardt DR, Lee SH, Yin X, Balynas AM, Rekate EC, Kraiss JN, Lang MJ, Walsh MA, Streiff ME, Corbin AC, Li Y, Funai K, Sachse FB, Chaudhuri D. EFHD1 ablation inhibits cardiac mitoflash activation and protects cardiomyocytes from ischemia. J Mol Cell Cardiol. 2022 Jun;167:1-14. doi: 10.1016/j.yjmcc.2022.03.002. Epub 2022 Mar 16. PubMed PMID: 35304170; PubMed Central PMCID: PMC9107497.
  6. Balderas E, Eberhardt DR, Lee S, Pleinis JM, Sommakia S, Balynas AM, Yin X, Parker MC, Maguire CT, Cho S, Szulik MW, Bakhtina A, Bia RD, Friederich MW, Locke TM, Van Hove JLK, Drakos SG, Sancak Y, Tristani-Firouzi M, Franklin S, Rodan AR, Chaudhuri D. Mitochondrial calcium uniporter stabilization preserves energetic homeostasis during Complex I impairment. Nat Commun. 2022 May 19;13(1):2769. doi: 10.1038/s41467-022-30236-4. PubMed PMID: 35589699; PubMed Central PMCID: PMC9120069.
  7. Sommakia S, Almaw NH, Lee SH, Ramadurai DKA, Taleb I, Kyriakopoulos CP, Stubben CJ, Ling J, Campbell RA, Alharethi RA, Caine WT, Navankasattusas S, Hoareau GL, Abraham AE, Fang JC, Selzman CH, Drakos SG, Chaudhuri D. FGF21 (Fibroblast Growth Factor 21) Defines a Potential Cardiohepatic Signaling Circuit in End-Stage Heart Failure. Circ Heart Fail. 2022 Mar;15(3):e008910. doi: 10.1161/CIRCHEARTFAILURE.121.008910. Epub 2021 Dec 6. PubMed PMID: 34865514; PubMed Central PMCID: PMC8930477.
  8. Van Keuren AM, Tsai CW, Balderas E, Rodriguez MX, Chaudhuri D, Tsai MF (2020). Mechanisms of EMRE-Dependent MCU Opening in the Mitochondrial Calcium Uniporter Complex. Cell Rep, 33(10), 108486.
  9. Lam PY, Thawani AR, Balderas E, White AJP, Chaudhuri D, Fuchter MJ, Peterson RT (2020). TRPswitch-A Step-Function Chemo-optogenetic Ligand for the Vertebrate TRPA1 Channel. J Am Chem Soc, 142(41), 17457-17468.
  10. Sommakia S, Houlihan PR, Deane SS, Simcox JA, Torres NS, Jeong MY, Winge DR, Villanueva CJ, Chaudhuri D (2017). Mitochondrial cardiomyopathies feature increased uptake and diminished efflux of mitochondrial calcium. Journal of molecular and cellular cardiology. 113:22-32.
  11. Chaudhuri D, Artiga DJ, Abiria SA, Clapham DE (2016). Mitochondrial calcium uniporter regulator 1 (MCUR1) regulates the calcium threshold for the mitochondrial permeability transition. Proc Natl Acad Sci U S A, 113(13), E1872-E1880. PMCID: PMC4822583
  12. Chaudhuri D, Sancak Y, Mootha VK, Clapham DE (2013). MCU encodes the pore conducting mitochondrial calcium currents. eLife, 2, e00704. PMCID: PMC3673318
  13. Sancak Y, Markhard AL, Kitami T, Kovacs-Bogdan E, Kamer KJ, Udeshi ND, Carr SA, Chaudhuri D, Clapham DE, Li AA, Calvo SE, Goldberger O, Mootha VK (2013). EMRE is an essential component of the mitochondrial calcium uniporter complex. Science, 342(6164), 1379-82. PMCID: PMC4091629
  14. Chaudhuri D, Clapham DE (2014). Outstanding questions regarding the permeation, selectivity, and regulation of the mitochondrial calcium uniporter. [Review]. Biochem Biophys Res Commun, 449(4), 367-9. PMID: 24792175
Last Updated: 7/29/25