Abhinav Diwan, MD, FACC, FAHA

Associate Professor
Internal Medicine
Cardiovascular Medicine
Associate Professor
Cell Biology and Physiology

Molecular Cell Biology Program

Research Abstract:

Our lab is investigating the regulation of lysosome function in physiology and disease. We have found that lysosomal degradative pathways are impaired in myocardial infarction, due to impaired autophagosome-lysosome fusion and transcriptional suppression of the autophagy-lysosome machinery, resulting in cardiomyocyte death. Ongoing studies are focused upon identifying the molecular mechanisms that regulate lysosome number and function under stress, in mammalian cells and C. elegans model systems. We are developing strategies to stimulate the lysosome machinery by calorie restriction, and translate these benefits to cardioprotection in myocardial infarction. We are also studying the molecular and cellular mechanisms that link lysosome dysfunction to development of hypertrophic cardiomyopathy in Danon disease, which results from loss of lysosomal membrane protein, LAMP2. In collaborative studies, we aim to determine the efficacy of stimulating lysosome biogenesis with activation of transcription factor EB (TFEB, a master regulator of the lysosome machinery) in countering amyloid plaque pathogenesis in Alzheimer’s Disease and enhancing beta-cell survival in diabetes.

Selected Publications:

Liu H, Javaheri A, Godar RJ, Murphy JT, Ma X, Rohatgi N, Mahadevan J, Hyrc K, Saftig P, Marshall C, McDaniel ML, Remedi MS, Razani B, Urano F, Diwan A. (*contributed equally) Intermittent Fasting Preserves Beta-cell Mass in Obesity-induced Diabetes via the Autophagy-Lysosome Pathway. Autophagy. 2017 Aug 30:0. doi: 10.1080/15548627.2017.1368596

Godar RJ, Ma X, Liu H, Murphy JT, Weinheimer CJ, Kovacs A, Crosby SD, Saftig P, Diwan A. Repetitive Stimulation of Autophagy-Lysosome Machinery by Intermittent Fasting Preconditions the Myocardium to Ischemia-Reperfusion Injury. Autophagy. 2015 Jun 23;PubMed PMID: 26103523.

Ma, X; Liu, H; Murphy, JT; Foyil SR, Godar, RJ; Abuirqeba, H; Weinheimer, CJ; Barger, PM and Diwan A. Regulation of TFEB-PGC1α Axis by BECLIN-1 Controls Mitochondrial Quality and Cardiomyocyte Death under Stress. Molecular and Cellular Biology. 2015 Mar 15;35(6):956-76. PMCID:PMC4333088

Yang KC, Ma X, Liu H, Kovacs A, Barger PM, Mann DL, Diwan A. TNF-receptor associated factor-2 mediates mitochondrial autophagy. Circulation Heart Failure. 2015 Jan;8(1):175-87. PMCID:PMC4303508

Xiao Q, Yan P, Ma X, Liu H, Perez R, Zhu A, Gonzales E, Burchett JM, Schuler DR, Cirrito JR, Diwan A*, Lee JM* (*contributed equally, co-corresponding authors). Astrocytic lysosome biogenesis facilitates Aβ clearance and attenuates amyloid plaque pathogenesis. The Journal of Neuroscience 2014: 34: 9607-9620. PMCID:PMC4099542

Ma X, Liu H, Foyil SR, Godar RJ, Weinheimer CJ, Diwan A. Autophagy is impaired in cardiac ischemia-reperfusion injury. Autophagy. 2012 Sep 1;8(9). PMCID:PMC3442889

Ma X, Liu H, Foyil SR, Godar RJ, Weinheimer CJ, Hill JA, Diwan A. Impaired Autophagosome Clearance Contributes to Cardiomyocyte Death in Ischemia-Reperfusion Injury. Circulation. 2012 Jun 26;125(25):3170-81. PMCID:PMC3397471

Ma X, Godar RJ, Liu H, Diwan A. Enhancing lysosome biogenesis attenuates Bnip3-induced cardiomyocyte death. Autophagy. 2012 Mar 1;8(3). PMCID:PMC3337840

Last Updated: 10/6/2017 9:52:04 AM

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