Role of Zfx in lymphocyte development and function

Columbia University Health Sciences, New York NY

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Abstract

DESCRIPTION (provided by applicant): Lymphocyte quiescence is a process not fully understood, but crucial in the function and maintenance of the immune system. Under normal conditions when the immune system is not activated by foreign invaders, lymphocytes remain in a quiescent state to prevent unprovoked immune responses and to protect against autoimmunity. This state of quiescence is actively controlled by various signaling pathways and transcription regulators. Identifying the molecular mechanisms controlling lymphocyte quiescence should increase our understanding of autoimmune diseases and facilitate novel approaches to their therapy. Preliminary data from our lab suggests that the transcription factor, Zfx (Zinc Finger protein encoded on the X chromosome), may be an essential regulator of lymphocyte quiescence and survival. Using various conditional knock out animal models of murine Zfx, the role of Zfx in lymphocyte development and quiescence will be determined through flow cytometry characterization of lymphoid compartments in these mice. The functional role of Zfx in T lymphocytes will be tested through molecular biology and immunological assays. Lastly, Zfx-dependent target genes and effector pathways will be identified through Microarray and biochemical approaches.