MSB LAB at IITI

We focus on a crucial inflammation-related adaptor of Toll-like receptors (TLR) called MyD88 adaptor-like (TIRAP). TIRAP contains a TIR domain required for mediating interactions with receptors on the membrane and with downstream signaling molecules. TIRAP represents a key mediator of TLR signaling in immune cells such as macrophages, where activation of TLR2 and TLR4 causes persistent inflammation in a TIRAP-dependent fashion. Following receptor-mediated detection of pathogenic ligands, TIRAP mediates various protein-protein interactions. The specific TIRAP interaction with its binding partner will determine the severity and type of inflammatory responses. Unraveling the protein-protein interactions of TIRAP would not only lead us to a greater understanding of the underlying signaling mechanisms that occur in the progression of various life-threatening chronic inflammatory conditions but would also guide us toward the development of important therapeutic strategies for disease treatment.

Figure- TIRAP interacting machinery in the activation of inflammatory signaling.

Colorectal Cancer (CRC) is closely associated with chronic inflammation, which can contribute to cancer progression. The tumor microenvironment (TME) can aid tumor cells in evading surveillance and clearance by immune cells, creating an internal environment conducive to tumor cell growth. Tumor-associated macrophages (TAMs) are the most abundant immune cells in the TME and interact with cancer cells. CRC cells release soluble factors and exosomes that reprogram macrophages to a growth-promoting phenotype, ultimately facilitating aggressive tumor progression. The aim of our research is to identify the molecular mechanisms behind macrophage phenotypic changes in response to exosomes. This understanding will aid in identifying novel targets and the development of effective therapeutics for treating colorectal cancer.

Figure- Kinetics study of macrophages pro-/anti-inflammatory cytokines expression in colorectal cancer microenvironment.