Representative Laboratory Projects for the Immunohematology Training Program

PAULA KAVATHAS LABORATORY
Molecular basis for lineage commitment of T cells into CD8+ T cells. The CD8 alpha and beta genes are closely linked on a 100 kb fragment in humans. They are coordinately expressed on most T cells in the peripheral blood but discoordinately expressed on natural killer cells (CD8alpha/alpha) and some T cells of the gut potentially involved in immunoregulation. To identify the multiple regulatory elements that determine CD8 expression, we mapped DNase I hypersensitivity sites, and matrix attachment regions. We are testing potential regulatory elements in transgenic animals. In addition, the state of chromatin is important for gene expression. We are studying chromatin structure in different cell types as part of the overall regulation of expression. Determining the transcription factors that are key for expression is another part of the puzzle.

MARK SHLOMCHIK LABORATORY
We study the mechanisms of induction and pathogenesis of graft vs. host disease. One focus is on chronic graft vs. host disease. We are investigating the roles of T cell cytokine polarization, antigen presentation and T regulatory cells in a mouse model of this syndrome. We are also investigating the mechanisms of graft vs. leukemia using a novel model of retroviral (bcr-abl) induced murine CML. In both these projects, we make extensive use of gene-targeted mice, as well as cell purification, FACS analysis, and
immunofluorescence analysis.