The work in our laboratory has centered on understanding the patho-physiological effects of shock/ tissue injury/ sepsis that lead to immune dysfunction and subsequent multiple organ failure in the critically ill trauma patient (through animal modeling and collaborative clinical studies). Over the years, we have described numerous deficits in both components of cell-mediated (T-cell, NKT-cell, gd T-cell, Treg-cell, etc) and innate (macrophage, neutrophil, dendritic cells) immune responsiveness induced by shock or sepsis, which are underpinned by alterations in cell signaling, protein translation and transcription patterns. Particular emphasis has been directed at defining the role of soluble mediators (e.g., IL-4, IL-10, IL-16, MCP-1, MIP-2/KC/IL-8, TGF-b, PGE2, NO, steroids, etc.), inhibitory receptors (e.g., PD-1:PD-L1/L2, BTLA:HVEM, FasL:Fas, etc.) and/or cellular pathways (e.g., p38 MAPKs, STAT 1/4/6, SOCS 1/3, Shp1/2, Rip1/3, NFkB, etc.) involved in orchestrating these changes in mouse models and critically ill patient.
We have also found evidence of alterations of the immune cell's apoptotic process and are actively examining the contribution of this pathway. It is our hope that, by understanding the cellular/molecular mechanisms which control these alterations in the traumatized or septic animal/patient, we will improve our ability to treat them.