Regulation of the innate immune response and its impact on disease

Research in my laboratory is focused on the role of receptor-mediated events in the pathogenesis of infectious and inflammatory processes. The discovery of the Toll-like receptors (TLRs) and their importance in the regulation of host responses to infection has focused attention on the complex interplay between pathogen genes and these host innate immune proteins in determining the outcome of infection. Our studies have demonstrated that pathogen-TLR interactions contribute to early control of infection (macrophage activation, type I interferon), recruitment of immune effector cells (chemokines) and the development of a sustained adaptive immune response (T and B cell activation and maturation). We have focused on host- and pathogen-derived proteins that regulate the magnitude and duration of the innate inflammatory response during viral infection and the impact of these factors on disease severity. Recently we have examined the role of innate immunity in the wound healing and the recruitment of stem cells involved in the regeneration of mucosal tissues. These studies point to the key role of innate immune receptor-triggered pathways in the initiation of healing and repair of damaged tissues following microbial or chemical insults as well as their significant role in disease pathogenesis.

Potential Rotation Projects

1. Expression of Toll-like receptors: Patterns of TLR expression in normal cells. Control of TLR receptor expression by environmental factors and cytokines. TLR expression in diseased tissues.



2. Role of TLRs in disease pathogenesis: Use of knockout and genetically defined animals to study the role of TLRs in the control of bacterial or viral diseases.



3. Structure-function studies of TLR signaling: Assessing the signaling activity of wild type and mutant TLRs (altered by site-directed mutageneis) using transient transfection and luciferase reporter gene analysis.