Dr. Sai Sudha Koka’s Lab

Research Goals

The Koka lab focuses on three areas:

1. Etiology of cardiovascular diseases
2. Developing novel therapeutic strategies for prevention and treatment of cardiovascular diseases in diabetic, obese and aging patients.
3. Cardiotoxicity of novel anti-cancer therapies

Cardiovascular disease pathogenesis:
Cardiovascular diseases (CVD) represent the leading cause of morbidity and mortality in the world. Our current understanding of the CVD pathogenesis is insufficient to control serious cardiovascular complications in majority of the patients who eventually succumb to the disease. Hence, there is a critical need for discovery of novel risk factors and pathways linked to CVD pathogenesis. In this context, the role of gut microbiome and gut microbe-derived metabolites on vascular disease pathogenesis has been recognized only in recent times. Our lab focuses on studying the molecular mechanisms mediating the response of endothelial and vascular smooth muscle cells to gut microbe derived metabolites. We discovered that gut microbial metabolites like trimethylamine-N-oxide (TMAO) induce inflammasome activation leading to endothelial dysfunction, vascular injury and atherosclerosis in mouse models.

Pre-clinical development of small molecule inhibitors for treatment of CVD:
Despite maximal therapeutic intervention with currently available treatment options, at least 50% residual risk remains in CVD patients. There is ongoing search for new drugs as well as repurposing FDA approved drugs for the treatment of CVD. We are currently focusing on investigating the therapeutic potential of novel small molecules which include inflammasome inhibitors, nanoparticle-based formulations and natural products in ex-vivo and in vivo models of CVD.

Drug-induced Cardiotoxicity:
Several chemotherapeutic agents like anthracyclines are known to be cardiotoxic. Despite their efficacy, their dose-dependent cardiotoxic side effects have been a major clinical concern that limits their clinical usage. The cardiotoxic effects of the most recent and novel chemotherapeutic agents are unknown. We have earlier demonstrated that phosphodiesterase-5 (PDE-5) inhibitor tadalafil attenuated cardiac dysfunction in doxorubicin-induced cardiomyopathy. Our lab focuses on identifying the cardiotoxic effects of novel agents and studying the pathogenesis of chemotherapeutic drug-induced cardiotoxicity.