Research

Ubiquitin Proteasome system (UPS) is the major protein degradation system in all eukaryotes. Proteasome is the catalytic megacomplex which degrades the damaged protein in a very regulated manner. However, in disorders like neurodegeneration, this degradation function is compromised. Interestingly, in the other hand proteasome degradation function is enhanced in disease like cancer…!! Hence, understanding these two opposite impairment mechanisms would offer a better insight of proteasome function under human pathology. We follow molecular cell biological approach to study those mechanisms in cellular disease models.

Targeted protein degradation approach uses a molecular glue that brings together the E3 ligase and the target protein; ubiquitinate the protein which resulted its degradation by proteasome. This approach mostly targeted the oncoproteins and other diseased-proteins for their degradation as therapeutics. In collaboration with synthetic chemistry labs we design, develop, synthesize and test the abilities of several PROTACs, molecular glues and small molecule inhibitors for their efficacy of positively modulating UPS function and disease-protein degradation in human pathologies. 

SARS-Cov2 viral infection affects several signaling pathways in the host cell. One of the key signaling pathways that the virus hijack for its own survival, is UPS pathway. A particular protease of SARS-Cov2 called - PLpro, has similar deubiquitinase and deISGylase activities that affect the host ubiquitinate landscape and protein homeostasis. We are trying to understand how PLpro can affect DUB and proteasome functions and interfere in host protein degradation pathways. We follow a structural, biochemical and cell biological approaches to understand this viral infection and the signaling alteration in the host body.