BM'S LAB

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Research Overview

G-protein Regulation in the Cellular Communication

Presently, India is going through rapid demographic-, environmental-, and lifestyle-related public health challenges, which has resulted in significant transitions in the magnitude and pattern of disease risk across the country particularly non-communicable diseases (NCD) including heart disease and chronic liver disease accounting >50% of deaths and representing a huge burden on Indian healthcare system. Aberrant activation of G protein-coupled receptors (GPCRs) and its modulators has now been implicated in these physiological aspects and identifying effective means to prevent or treat these disorders represents a critical barrier to the country’s progress. 

 

GPCR receptors constitute a large family of surface proteins critically involved in variety o physiological functions. One third of the modern day medicines was generated targeting this signalling. But it is surprising that Regulator of G protein signaling (RGS) and Activators of G-protein signalling (AGS) proteins have received very less focus as potential candidates towards altering these signalling processes. RGS proteins negatively regulate heterotrimeric G protein signalling and function as GTPase-activating proteins for G protein subunits, an activity bestowed by their RGS domain thereby enhancing the shut-off mechanism for G protein signaling. 

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In this line, the research projects carried out by Dr. Maity’s group investigates how G-protein signaling and its regulators/modulators like RGS/AGS proteins contributing to ‘onco-cardiology’ (chemotherapy-induced heart complication particularly hypertrophy, fibrosis and transition to heart failure), diabetic cardiomyopathy, its impact of multiple vital organs especially heart-liver axis, drug-induced liver injury resulting from common medications and NAFLD and drug-delivery platforms.

 

The research program of Dr. Maity centers around how G-protein dependent/independent mechanism employ damage to a single tissue, resulting from exposure to cytotoxic stress, propagates across the organ and throughout the body by autocrine/paracrine mechanism due to the release of variety of inflammatory and fibrotic factors into the local microenvironment and, ultimately peripheral circulation. To prevent this pathogenic multi-organ crosstalk, a comprehensive understanding of both initiating events and mechanisms that maintain, amplify, and propagate these signals is required. Throughout his career, Dr. Maity has systematically dissected the role of G-protein signaling and its determinants in these physiological processes mostly heart/liver and identified a number of novel, druggable targets that have clinical utility in treatments or adjuvants across several NCDs.

BM'S& LAB

In collaboration with chemists, we are also trying to develop different kind of drug-delivery platforms using short-peptide based self assembled structures towards targeted delivery of chemo-drugs to minimize off-target effects especially in heart and evaluating the potential of them to perturb G-protein mediated signalling cues. 

 

The research work is highly aligned with the national program ‘Prevention and control of cancer, diabetes, cardiovascular diseases and stroke’ (NPCDCS), Ministry of Health, Family Welfare and National Health Mission. This research programs have been continuously supported from several government agencies including DBT, ICMR, DHR, DRDO, DAE, SERB and DST.