Assistant Professor, Department of Microbiology and Physiological Systems
UMass Medical School University of Massachusetts, USA
The innate immune system must tightly regulate the temporal dynamics and the extent of inflammatory responses to promote clearance of invading pathogens without excessive tissue damage. Pathogens are detected by pattern recognition receptors such as the Toll-like receptors (TLRs) which recognize microbial components and activate intracellular signaling pathways leading to the transcriptional induction of genes that are critical for protective inflammatory responses. Systems biology studies have demonstrated that TLR-induced inflammatory responses are controlled by the integration of transcriptional “on” and “off” switches with “amplifiers” and “attenuators”, altogether forming gene regulatory circuits. Dynamic interplay of transcription factors in these circuits determines the transcriptional profile of a target gene and ensures appropriate host response to invading pathogens. However, pathogens are equipped with a wide range of virulence factors to subvert host protective responses and to establish a niche for their survival and proliferation. Virulence factors dynamically interact with host transcription factors and chromatin remodeling proteins to rewire and reprogram host gene regulatory circuits. In my lab we aim at elucidating the mechanisms and consequences of pathogen-induced reprogramming of host gene regulatory networks. Understanding these complex host-pathogen interactions is critical for the discovery of novel antiviral therapies and rational vaccine design and development.
Innate immunity, Systems Immunology