Research SummaryIntermediate Fellowship research summary
Our ability to elicit an appropriate inflammatory response is critical for pathogen clearance subsequent to an infection. However, deregulated inflammatory response underlies several human pathologies that include inflammatory disorders, autoimmune diseases and cancers. Therefore, it is of interest to fully understand the physiological mechanisms those control inflammatory response, both its amplitude and duration.
The canonical arm of NF-kappaB signaling plays a central role in mediating inflammatory response upon pathogen sensing. However, a number of cross-regulatory mechanisms have been identified those connect the canonical module with other signaling modules in a network. Indeed, in physiological settings, multiple stimuli are often impinged upon a single cell, which generates the potential for crosstalk between these apparently insulated cell-signaling modules. Our research interest lies in understanding the implications of such interdependent regulations of “discrete” cell-signaling modules in infection and immunity.
In particular, we will address the role of constituents of the tissue microenvironment in modulating NF-kappaB mediated inflammatory response through signaling crosstalk. In a multidisciplinary program, we will combine biochemistry, molecular biology, mouse genetics and mathematical modeling to identify and characterize the cross-talk elements hardwired within the signaling network and to decipher their role in regulating dynamic properties of NF-kappaB signaling.