Associate Professor, Cellular & Integrative Physiology
Chair, Department Recruitment Committee
Chair, A. Ross McIntyre Cardio-Renal Seminar
Director, Cardiopulmonary Function in Health and Disease Program
PhD 2006, Banaras Hindu University, India
Specialty: Cardiovascular Diseases with Diabetes
Major Interest: MicroRNomics and molecular mechanisms of diabetic cardiomyopathy
Diabetes doubles the risk of heart failure. Intensive control of blood glucose levels could not reduce the risk of heart failure in diabetic patients compared to the less intensively glucose controlled diabetic patients. This suggests that diabetes-induced heart failure is beyond hyperglycemia. What triggers heart failure pathogenesis in diabetes at the molecular level remains nebulous.
Diabetes-induced heart failure differs from non-diabetic heart failure in increased myocardial lipotoxicity and higher risk of heart failure in women compared to men. Our research interest is to decipher molecular mechanisms underpinning diabetic cardiomyopathy for developing novel therapeutics. Our research projects primarily focused on investigating molecular regulation of metabolic remodeling, cell death, and mitochondrial dysfunction in the diabetic heart to develop novel miRNA mimic, hydrogen sulfide donor, and matrix metalloproteinase-9 (MMP9) inhibitor-based therapies for diabetic cardiomyopathy.
Cardiomyocytes are contractile cells with large number of mitochondria that utilize metabolic substrate to produce energy (ATP), which is required for constant contractility of the heart. In the diabetic heart, reduced glucose uptake causes metabolic remodeling where cardiomyocytes are forced to utilize more fatty acids. Fatty acids are less energy efficient and require more oxygen per ATP molecule than glucose. Fatty acid consumption increases mitochondrial stress leading to mitochondrial damage and dysfunction in the diabetic heart. Damaged mitochondria are inherently degraded and recycled by mitophagy. In the diabetic heart, mitophagy is impaired that results in accumulation of damaged mitochondria exacerbating mitochondrial damage, which yields excessive reactive oxygen species (ROS) causing oxidative stress. Stressed cardiomyocytes ultimately die via different cell death signaling mechanisms. Myocardial cell death mechanisms are elaborated in this publication: https://journals.physiology.org/doi/full/10.1152/ajpheart.00259.2019. Due to the limited regeneration capacity, death of cardiomyocytes promotes adverse cardiac remodeling leading to diabetic cardiomyopathy and heart failure.
Mentoring is a major part of my academic goal. My graduate students have received several national awards including 1st place for The Science Coalition’s Fund It Forward Student Video Challenge 2019 ( Video Link) and 2nd place in Research!America’s 2020 Flash Talks Competition at the National Health Research Forum (Link: https://www.unmc.edu/news.cfm?match=26235) . Graduate students have also received the NIH’s F31 fellowship and UNMC’s Program of Excellent Assistantship.