The dual goals of this proposal are to investigate the function of microRNAs in hematopoietic/T cell development and to establish the applicant as an independent investigator. MicroRNAs represent a novel class of small regulatory RNAs. miRNAs control gene expression by base pairing with miRNA-recognition elements found in their mRNA targets. The effects of miRNAs in gene expression regulation are pleiotropic, miRNAs control cellular proliferation, apoptosis and development, although many of the genes that mammalian miRNAs regulate are unknown. The role of miRNAs in T lymphocytes and their development is completely unknown. Studies to address the function of miRNAs in hematopoietic/T cell development promise to unravel novel pathways that control hematopoietic/lymphocytic development and at the same time enhance our understanding of the function of miRNAs. In Aim #1, mRNA targets for mammalian miRNAs will be identified. An experimental-computational approach is presented along with strategies for validation of miRNA targets. In Aim #2, the function of miRNAs in murine hematopoietic/T cell development will be investigated. The applicant has spent the last several years for a career as a physician-scientist, through her prior research training in the molecular biology of steroidogenesis and clinical training in Internal Medicine and Rheumatology. Drs. Warren Pear, Zissimos Mourelatos and Philip Cohen, recognized for their expertise in the fields of T cell development and Immunology (Drs. Pear and Cohen) and microRNA biology (Dr. Mourelatos), will sponsor the candidate's scientific development. The quality of the research facilities and the diversity of the resources available at the Sponsoring Institution in combination with the intellectual and academic strength of the sponsors, provide an ideal setting for the conduction of the proposed studies.