Education & Research

Research

Research Interests:  
I am generally interested in mechanisms of immune repertoire diversification.  My research program is currently focused on studying various aspects of V(D)J recombination, the process by which immunoglobulin and T cell receptor genes are assembled during lymphocyte development.  V(D)J recombination is initiated by the RAG1 and RAG2 proteins, which together introduce DNA breaks in the antigen receptor loci, which are subsequently repaired by components of the non-homologous DNA end-joining (NHEJ) repair pathway (Fig. 1).  The laboratory has two major ongoing projects.  The first project is primarily biochemical, and is broadly aimed at identifying and characterizing protein-DNA complexes involved in cleavage and repair phases of V(D)J recombination.  We are particularly interested in learning how the DNA ends produced by RAG cleavage are transferred to the NHEJ apparatus for repair.  We believe NHEJ is facilitated by the associated of NHEJ factors with pre-cleavage RAG complexes, as we have recently published evidence for the association of the Ku70/Ku80 with full-length RAG1.  The second project involves determining whether enforced expression of catalytically inactive RAG1 in mice can impair secondary V(D)J recombination events triggered by engagement of self-antigen (receptor editing) or in response to immunization (receptor revision), and whether defects in these processes increase susceptibility to malignancy or autoimmune disease.  These research projects are or have been supported by both intramural and extramural grants, including grants awarded by the National Institutes of Health and the American Cancer Society.