Research Summary

Autophagy, Inflammation, and innate immunity

 

 

Autophagy
Autophagy is a fundamental catabolic process involved in cellular garbage degradation and recycling thus maintaining cellular metabolism and homeostasis. It is essential for cellular differentiation and embryonic development in mammals. In addition to these basic functions, autophagy plays several specialized roles in eukaryotic cells including cell-autonomous defense against intracellular pathogens and control of chronic inflammation. Not surprising, defects in autophagy have been linked to several diseases including cancer, 
neurodegeneration and cardiac pathologies.
My major research interests are:

  1. To understand the molecular mechanisms of autophagy regulation.
  2. To understand the mechanisms by which autophagy accomplishes anti-microbial and anti-inflammatory functions.
  3. To understand the mechanisms by which autophagy degrades disease-related misfolded proteins or protein aggregates.

Understanding the role of IRGM-mediated innate immune responses in diseases

Immunity-related GTPase M (IRGM) belongs to IRG (Immunity-related GTPase) gene family which is one of the strongest resistance systems to intracellular pathogens in mammals. The IRGM gene was pseudogenized during evolution and then by series of amazing genetic alterations, IRGM resurrect in immediate ancestors of humans. Therefore, it is not surprising that this evolutionary selected gene is protective in several human diseases and inactivating polymorphisms in it are strongly associated with several infectious and inflammatory diseases/conditions such as tuberculosis (TB), Crohn's disease, gastric cancer and severe sepsis. Further, IRGM is functionally implicated in other chronic inflammatory diseases/conditions including leprosy, atherosclerosis, and ischemic stroke. However, the mechanism/s by which human IRGM controls cellular inflammation is not known. In the first part of the proposal, I will determine that how human IRGM restrains excess inflammation in cells. IRGM is an important anti-microbial autophagy-factor and hence hijacked by several RNA viruses including HIV. In the second part of the proposed work, I will determine that how HIV subverts IRGM-mediated antimicrobial autophagy and will also define that how this action of HIV is beneficial for Mycobacterium tuberculosis survival during HIV-TB co-infection.