Jonathan Kaye, PhD
|Professor, Biomedical Sciences|
Awards and Activities
|Major Symposium Invited Speaker and Co-Chair, AAI Annual Meeting||2009|
|Member, Investigations on Primary Immunodeficiency Diseases Review Panel, NIH||2009|
|Member, Special Emphasis Review Panels, Center for Scientific Review, NIH||2009|
|Section Editor: Journal of Immunology||Current|
|Associate Editor: Journal of Immunology||1993 - 1999|
|American Association of Immunologists||1991|
As a site of continuing somatic cell differentiation throughout life, the immune system provides a unique opportunity to reveal fundamental pathways of gene regulation and cell fate decisions. We are interested in understanding the molecular regulation of T cell development, with a particular focus on lineage diversification in the thymus. This process is initiated by recognition of major histocompatibility complex-encoded antigens on resident epithelial cells by a cell surface antigen receptor expressed by immature thymocytes. Activation of this receptor leads to a cascade of changes in gene expression, ultimately linking the function of the T cell to antigen receptor specificity. This process is of fundamental importance to establishment of a diverse but self-tolerant immune system. In addition, we are interested in aspects of mature T cell function as it relates to germinal center formation, as well as molecular regulation of lymph node organogenesis. Finally, our work on a family of nuclear proteins has led to recent focus on the function of one of these proteins in relation to cancer.
Most recently, we have identified a novel family of nuclear factors, the founding member of which plays critical roles in development of the immune system. We have also linked signaling pathways activated by the T cell antigen receptor to downstream transcriptional regulators that control T cell differentiation in the thymus. Earlier work was at the forefront of research in identifying the T cell antigen receptor and using transgenic mice to elucidate the biological role of this receptor in regulating lineage commitment in the thymus.
Current investigations include:
Dissection of the mechanism of action of a nuclear factor. identified in this laboratory. in development of multiple lineages of T lymphocytes; role of this nuclear factor in lymph node organogenesis and development of natural killer cells; molecular regulation of the development of germinal center formation; role of a related transcriptional regulator in breast cancer.
- Aliahmad P, Kaye J: Development of all CD4 T lineages requires nuclear factor TOX. J. Exp. Med., 205(1): 245-56, 2008
- Krieg C, Boyman O, Fu YX, Kaye J: B and T lymphocyte attenuator regulates CD8+ T cell-intrinsic homeostasis and memory cell generation. Nat. Immunol., 8(2): 162-71, 2007
- Aliahmad P, O'Flaherty E, Han P, Goularte OD, Wilkinson B, Satake M, Molkentin JD, Kaye J: TOX provides a link between calcineurin activation and CD8 lineage commitment. J. Exp. Med., 199(8): 1089-99, 2004
- Wilkinson B, Chen JY, Han P, Rufner KM, Goularte OD, Kaye J: TOX: an HMG box protein implicated in the regulation of thymocyte selection. Nat. Immunol., 3(3): 272-80, 2002