Paras Kumar Mishra


Associate Professor, Cellular & Integrative PhysiologyWebsite picture
Director, Cardiopulmonary Function in Health and Disease Program
Chair, A. Ross McIntyre Cardio-Renal Seminar
 
PhD 2006, Banaras Hindu University, India
Specialty: Cardiovascular Diseases with Diabetes
Major Interest: MicroRNomics and molecular mechanisms of diabetic cardiomyopathy
 
 

In the diabetic heart, reduced glucose uptake into cardiomyocytes causes metabolic remodeling where cardiomyocytes are forced to utilize more fatty acids. Fatty acids require more oxygen per ATP molecule than glucose and thereby increases mitochondrial stress and dysfunction in the diabetic heart. Damaged mitochondria are not fixed rapidly due to impaired mitophagy, resulting in excessive reactive oxygen species (ROS) production leading to oxidative stress. Stressed cardiomyocytes in the diabetic heart ultimately die via different cell death signaling mechanisms. Death of cardiomyocytes promotes adverse cardiac remodeling such as hypertrophy and fibrosis, leading to cardiac dysfunction.

Our research is focused on understanding molecular mechanisms underlying mitochondrial damage, cell death, and cardiac dysfunction in order to develop a therapeutic intervention for diabetic cardiomyopathy. We have found that miR-133a, which is downregulated in the diabetic heart, plays a crucial role in diabetic cardiomyopathy. By using cardiac-specific miR-133a transgenic mice, we showed that miR-133a upregulation can prevent metabolic remodeling in the diabetic heart and could prevent diabetic cardiomyopathy. We know that exercise training has beneficial effects in the heart. We demonstrated that exercise training ameliorates diabetic cardiomyopathy, potentially by upregulating hydrogen sulfide (H2S). Moreover, H2S donor treatment mitigates adverse cardiac remodeling and cardiac dysfunction in diabetes. Matrix metalloproteinase-9 (MMP9) is upregulated in the diabetic heart and is pro-fibrotic. We have developed a novel diabetic mouse strain with targeted deletion of MMP9 and reported that MMP9 inhibition is cardioprotective to the diabetic heart.

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.

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