Research Approaches

Much of our current research focus is on Regulator of G protein Signalling (RGS) proteins.  They serve as key regulators of GPCR signalling pathways. RGS proteins canonically function as GTPase accelerating protein for heterotrimeric G protein alpha, thereby, acts as critical determinants of magnitude and duration of the cellular response to GPCR stimulation. RGS family proteins have been shown to clinically associate with different human disease conditions.  That’s why targeting RGS proteins holds a great promise for drug development. Our primary interest is R7 subfamily of RGS proteins and its binding partner atypical Gβ subunit Gβ5. We emphasize on discovering G-protein dependent & independent molecular and cellular mechanisms of RGS proteins in disease biology.

 

Research Overview

The primary emphasis of Biswanath Maity research laboratory is focused on fundamental principles that modulate signalling through G-protein coupled receptors in different physiological complications. They are combining experimental and computational methods to study the roles of different modulators of GPCR signalling in development of cardiovascular and cancer phenotype. GPCR signalling is well established in different physiological phenomenon but the role of its regulators is not well known which limits the development of better therapeutics. It is really surprising that much priority has not been given to the G-protein regulators keeping the fact that more than 70% of the market available drugs function through G-protein signalling. We leverage in vivo & in vitro system, computational approaches and isolated primary cells to analyze the diversity of functions of different G-protein modulators in developing cardiovascular and cancer manifestations.

 
 

Cardiovascular Research

We seek to identify the impact of R7RGS proteins in development of cardiac fibrosis, hypertrophy, cardiomyopathy and heart failure using different kind of in vivo model system.  We are also interested to discover the impact of G-protein mediators in the transition of hypertrophy to heart failure and mechanistically dissect the impact of TGF-b signalling and oxidative stress in this phenotype. The intricate regulation of RGS proteins with CaMKII (Ca2+/calmodulin dependent kinase II) in mediating these physiological complications are also major point of our interest.

In addition, we are also trying to dissect how the pain killers induce cardiac complications. Non-steroidal anti-inflammatory drugs (NSAIDs) are in use as analgesics worldwide but are often associated with cardiovascular complications. Use of NSAIDs increased the coronary events by 30-100% with heart failure risk doubling for all drugs tested. As a result, beginning in 2015, the FDA has required warnings regarding potential cardiovascular complications associated with these compounds on the labels of all prescription and non-prescription NSAIDs, a decision backed by the American Heart Association. We believe dissecting the underlying mechanism will be helpful to enhance the efficacy of this popular class of medicine for better healthcare.

 

Cancer Biology Research

BM laboratory is interested in studying the intricate molecular mechanisms by which RGS proteins regulates cell function, and how their perturbation go awry in cancer phenotype.  We have a long-standing interest in RGS function in oncogenic regulation and cellular transformation which play important roles in physiology and in the development of cancer and inflammatory diseases.  

Our current focus is on defining the function and regulation of RGS proteins in cancer using a combination of cellular, molecular, and genetic approaches. We seek to identify how R7RGS proteins functions to regulate different stimuli induced epithelial to mesenchymal transition, cellular senescence, interaction with other genetic & epigenetic modifiers. In addition we look for the effects of different biological modifiers for their G-protein dependent & independent effects for development of novel therapeutics.

© 2018 by Biswanath Maity et al.