Primarily interested in T cell development in the thymus. We study how selection processes shape the T cell repertoire to achieve a highly effective and self-tolerant adaptive immune system. Current research is focused on these four topics:
Positive selection: This is a crucial stage in T cell development, where MHC restricted progenitors are selected from a random pool. We are systematically studying the gene changes that occur in the T cell progenitor during positive selection and how they support the multiple facets of this event (e.g. survival, migration, allelic exclusion, etc). We are also exploring how cortical epithelial cells support the process of positive selection
Negative selection: One of the ways the immune system copes with self-reactive T cells is to eliminate them from the repertoire. We developed a highly physiologic in vivo mouse model to study the specific antigen presenting cell types involved and the timing and anatomic location of negative selection. We are also exploring why some self- reactive cells undergo apoptosis, but others are selected to become regulatory T cells or NKT cells.
Thymic Emigration: The lab is currently interested in the final stages of maturation that occur prior to migration of the progenitor from the thymus to the periphery. We seek to understand how the functional competence of the cell is eventually switched from apoptosis to proliferation, and the signals, molecular factors, and anatomic structures involved in emigration itself. Recent studies have focused heavily on the transcription factor KLF2.
The Human T cell repertoire: We have a unique collaboration with a clinical virology group to study immune responses in humans that are at high risk for natural infection with a gamma herpesvirus (Epstein Barr Virus or EBV). In addition to documenting the precise changes that occur during the innate and adaptive immune response to this virus, we are exploring how the pre-immune T cell repertoire in such individuals is predisposed to make a pathologic response to this virus (infectious mononucleosis).