Dr. GPCR Podcast

About Dr. Prasenjit Saha

I conducted my doctoral research at the Indian Institute of Science, Bangalore, India, to investigate the mechanisms behind rare mitochondrial diseases, which can lead to heart failure, muscle fatigue, and neurodegenerative disorders. I am now working at the Cleveland Clinic in Ohio, USA, studying the gut microbiome and its impact on cardiovascular disease (CVD). Specifically, I am interested in understanding dysregulated G-protein coupled receptor (GPCR) signaling linked to atherosclerosis and diabetes. My research goal is to identify novel cellular target receptors of human gut microbe-derived metabolites that are pathologically linked to CVD. Discovering these receptors would be a significant breakthrough in cardiovascular biology as they could be targeted for therapeutic purposes.

During my post-doctoral research, I was part of a study that identified the receptors of a novel human gut microbe-derived metabolite called phenylacetylglutamine (PAG), which is linked to cardiovascular disease. This study demonstrated that PAG is a potential diagnostic marker for CVD as it causes serious fatal conditions such as thrombus formation, which can block blood vessels. In this study, I discovered adrenergic receptors (α2A, α2B, and β2-adrenergic receptors) that serve as the gut microbial metabolite (PAG) receptor and characterized the receptor-metabolite interaction.

More recently, I have shifted my focus to identifying allosteric modulators of host G-protein-coupled receptors (GPCRs) that contribute to cardio-metabolic disorders. Traditional drug discovery efforts have focused on agonists and antagonists that bind to the orthosteric site of the receptor. However, the pursuit of allosteric modulators has gained attention as they have the potential to fine-tune cellular responses with greater selectivity among the subtypes of GPCRs. My long-term plan is to conduct research in the field of receptor biology, with a focus on GPCRs. They are the largest, most versatile, and most ubiquitous class of plasma membrane receptors and serve as targets for more than one-third of all prescribed drugs currently used in the treatment of human diseases all over the world.

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