Primary focus of my lab is to understand the molecular basis of heart failure, particularly, the role played by the chromatin remodeling enzymes in muscle gene regulation, cellular senescence and cardiac hypertrophy and fibrosis. Heart failure is a pathological state in which the heart is unable to pump blood at a rate commensurate with requirements of the metabolizing tissues. It is usually caused by a defect in myocardial contraction. Reduced myocardial contractile function may reflect a decrease in number of viable myocytes, dysfunction of viable myocytes, or alterations to the intrinsic contractile activity of individual myocytes. At the molecular level, several abnormalities have been observed, including alterations in the expression of numerous genes that are central to the normal structure and function of the heart; however, the basic mechanism of heart failure is not yet fully understood. With recent advancements in cell biology, it has become clear that factors modifying chromatin structure, e.g. histone deacetylases, acetyltransferases and sirtuins play a fundamental role in this process. In addition to modifying chromatin structure, these enzymes also play a role out side the nucleus. We are trying to understand how these enzymes modify mitochondrial proteins and regulate the cell-survivability and contractile function, in response to various pathophysiological stresses, including obesity/diabetes, hemodynamic overloads and aging.
All India Institute of Medical Sciences
New Delhi
MS and PhD - Physiology and Pharmacology
1985
University of Chicago
Chicago
Post-doctoral training (mentor Dr. Radovan Zak) - Cardiac cell biology
The Multifaceted Role of Sirtuins in Inflammatory Bowel Diseases.
The Multifaceted Role of Sirtuins in Inflammatory Bowel Diseases. Am J Physiol Gastrointest Liver Physiol. 2025 Apr 29.
PMID: 40298096
Characterization and molecular targeting of CFIm25 (NUDT21/CPSF5) mRNA using miRNAs.
Characterization and molecular targeting of CFIm25 (NUDT21/CPSF5) mRNA using miRNAs. FASEB J. 2025 Jan 31; 39(2):e70324.
PMID: 39812508
The nuclear sirtuin SIRT6 protects the heart from developing aging-associated myocyte senescence and cardiac hypertrophy.
The nuclear sirtuin SIRT6 protects the heart from developing aging-associated myocyte senescence and cardiac hypertrophy. Aging (Albany NY). 2021 05 02; 13(9):12334-12358.
PMID: 33934090
Skeletal muscle-specific over-expression of the nuclear sirtuin SIRT6 blocks cancer-associated cachexia by regulating multiple targets.
Skeletal muscle-specific over-expression of the nuclear sirtuin SIRT6 blocks cancer-associated cachexia by regulating multiple targets. JCSM Rapid Commun. 2021 Jan-Jun; 4(1):40-56.
PMID: 34212132
Is nuclear sirtuin SIRT6 a master regulator of immune function?
Is nuclear sirtuin SIRT6 a master regulator of immune function? Am J Physiol Endocrinol Metab. 2021 03 01; 320(3):E399-E414.
PMID: 33308014
The nuclear and mitochondrial sirtuins, Sirt6 and Sirt3, regulate each other's activity and protect the heart from developing obesity-mediated diabetic cardiomyopathy.
The nuclear and mitochondrial sirtuins, Sirt6 and Sirt3, regulate each other's activity and protect the heart from developing obesity-mediated diabetic cardiomyopathy. FASEB J. 2019 10; 33(10):10872-10888.
PMID: 31318577
Cellular mechanisms promoting cachexia and how they are opposed by sirtuins 1.
Cellular mechanisms promoting cachexia and how they are opposed by sirtuins 1. Can J Physiol Pharmacol. 2019 Apr; 97(4):235-245.
PMID: 30407871
SIRT2 deacetylase regulates the activity of GSK3 isoforms independent of inhibitory phosphorylation.
SIRT2 deacetylase regulates the activity of GSK3 isoforms independent of inhibitory phosphorylation. Elife. 2018 03 05; 7.
PMID: 29504933
SIRT2 regulates oxidative stress-induced cell death through deacetylation of c-Jun NH2-terminal kinase.
SIRT2 regulates oxidative stress-induced cell death through deacetylation of c-Jun NH2-terminal kinase. Cell Death Differ. 2018 09; 25(9):1638-1656.
PMID: 29449643
The histone deacetylase SIRT6 blocks myostatin expression and development of muscle atrophy.
The histone deacetylase SIRT6 blocks myostatin expression and development of muscle atrophy. Sci Rep. 2017 09 19; 7(1):11877.
PMID: 28928419
Member of the Scientific Advisory Board
International Academy of Cardiology
2016
Distinguished Fuculty
American Society of Nepharology
2016
Vincenzo Panagia Distinguished lecture award
University of Manitoba
2015
Fellow of American Heart Association (FAHA)
Basic science council of American Heart Association
2008
Senior Reserach Fellowship
American Heart Association
1989 - 1991
Upjohn Award for the best research paper
International Society of Heart Reserach
1987
Institutional Award of merit
All India institute of Medical Sciences, New Delhi
1984
National Merit Scholarship
Board of Education Government of India
1980