Mishra Lab

The prevalence of cardiovascular pathologies, especially Heart Failure with Preserved Ejection Fraction (HFpEF), is increasing, affecting an estimated 18 million adults. This number is anticipated to rise by 46% by 2030. Epidemiological studies emphasize the dual impact of obesity: it's not only a significant risk factor for HFpEF but also a disruptor of intracellular second messenger signaling. The Mishra Lab, led by principal investigator Sumita Mishra, Ph.D., is focused on unraveling the complexities of cyclic guanosine monophosphate (cGMP) signaling anomalies in cardiometabolic diseases and HFpEF. We're particularly interested in the role of specific Phosphodiesterases (PDEs) in modulating both cGMP and cAMP pathways. Preliminary findings indicate that PDE9A inhibition may offer a promising therapeutic avenue, potentially mitigating cardiometabolic dysfunctions by adjusting metabolism. As we investigate cyclic nucleotide modulation and natriuretic peptide dynamics, we aim to identify the subcellular domains influenced by PDE5 and PDE9, emphasizing their roles in the mitochondrial signalosome and its interplay with metabolic flux and epigenetic shifts.

In 2022, both the American Heart Association and the American College of Cardiology endorsed exercise training and lifestyle modifications for heart failure patients when appropriate. However, the precise mechanisms by which exercise benefits these patients, particularly those with cardiometabolic syndrome, remain to be elucidated. Concurrently, we're examining the impact of lifestyle changes, especially aerobic exercise, on these molecular pathways in hopes of discovering novel therapeutic strategies for cardiometabolic disorders.