David Center M.D.
Office: 72 E.Concord St R-Bd
Dr. Center’s laboratory studies the function of human CD4 and regulation of the cell cycle in T cells. The Center laboratory discovered, cloned and characterized most of the biologic functions of Interleukin (IL-16). Using functional and microarray analyses they are exploring the signal transduction pathways associated with CD4 activation by IL-16 and the mechanisms by which CD4 functions as a chemotactic factor and growth factor receptor. Most recently this work has led to the discovery that IL-16-CD4 interactions result in selective chemotaxis of CD4+CD25+ regulatory T cells and that IL-16 is sufficient to induce differentiation of CD4+CD25 T cells to express FoxP3 and acquire regulatory T cell functions. One major part of the laboratory looks at the role IL-16 plays in development of regulatory T cells using knock-out and over expressing mice and animal models of Th1 and Th2 driven inflammation, including a model of airway inflammation. The second focus of work in Dr. Center’s laboratory relates to the study of a nuclear protein complex that targets histone deacetylases to specific transcription factors and represses transcription of a select family of genes involved in maintenance of T cell quiescence. The complex is regulated by T cell activation at the level of the scaffold protein as the enzymatically active components do not change with cell activation or during the cell cycle. Mutations and deletions in the scaffold protein, the precursor for IL-16 are common in T cell lymphomas and replacement of nuclear expression of the normal protein results in return to a normal cell cycle profile and loss of malignant characteristics. The current studies are exploring the mechanisms of regulation of pro-IL-16 transcription itself as a regulatory element in T cell cycle and its role in the development of anergy.