Research Abstract:

The innate immune system defends the host from pathogens and cancer while the adaptive immune system is being mustered. By providing early detection and control, it can also shape the T and B cell response. We study various aspects of the innate immune system in the context of murine cytomegalovirus (MCMV) and cowpox virus (CPXV) infections, as well as tumors.

Natural killer (NK) cells constitute a major constituent of the innate immune system. Interestingly, innate immune cells are often distinguished from adaptive immune cells by several features which include “memory,” a feature classically associated with adaptive but not innate immunity. Recently, however, we discovered that NK cells have memory-like properties that could be exploited to enhance immune responsiveness.

We are particularly interested in NK cell receptors that recognize ligands on their infected or tumor cell targets. Over the years, we have identified and characterized NK cell inhibitory receptors that recognize major histocompatibility complex class I molecules on the target cell. These inhibitory receptors block the function of NK cell activation receptors that recognize other target cell surface ligands, including molecules encoded by viruses. These receptors display profound allelic polymorphisms, as recently shown by our work with array-based comparative genomic hybridization.

Together, the NK cell receptors dictate whether or not the NK cell will kill normal or diseased cells. While this is related to their recognition of ligands on their cellular targets, it is also clear that they have other effects on NK cell function, i.e., tolerance, which also includes a recently described process termed “licensing” and “anergy” due to engagement of ligands expressed on self-tissues by the inhibitory receptor or activation receptor, respectively.

Our work on the role of NK cells in anti-pathogen defense has led to studies of innate immune responses to large DNA viruses, MCMV and CPXV. We are especially interested in how these viruses interact with the host, since much of their genomes is dispensable for in vitro growth and replication, i.e, they encode molecules that modulate the immune system. MCMV and CPXV are amenable for such analyses since their natural reservoirs are rodents and thus, immunopathogenesis studies in mice are applicable to host-pathogen interactions.

Selected Publications:

Last Updated: 2/8/2012 8:20:19 AM