This COBRE grant has 4 major objectives: 1.) The development of a strong mentoring group of established investigators; 2.) The enhancement of infrastructure support through the development of core laboratories, administrative support, and resources; 3.) The recruitment and retention of young and established faculty at Roger Williams Medical Center (RWMC) and collaborating Providence institutions (Brown, Miriam Hospital, and Rhode Island Hospital) in order to continue the establishment of a major stem cell research center for the state, region, and country; and 4.) To define the capacity of marrow cells to produce skin and muscle cells, and to define the clinical potential of these approaches in murine wound healing and muscular dystrophy models, and to establish Vector Systems to use siRNA to inhibit stem cell transcriptional pathways and to assess the effect on the stem cell phenotype, beginning with PU.1. We have assembled an experienced group of scientists who will mentor 3 promising young investigators and are prepared to mentor others in different research areas. The work is thematically coordinated around stem cell biology and plasticity and transcriptional regulation of stem cells and the potential for using siRNA to redirect stem cell differentiation. The 3 projects and their P.I.s are: Project 1 - Dr. Evangelos Badiavas - studies on the capacity of marrow cells to transdifferentiate (or convert) to skin cells and heal wounds. Project 2 - Dr. Mehrdad Abedi - the capacity of marrow cells to produce skeletal muscle cells and treat muscle disorders. Project 3 - Dr. Bharat Ramratnam - Stem cell gene modulation by RNAi. These scientific projects are supported by an Administrative Core, A Cell Sorter/Flow Cytometry Clore, and a Cell Phenotyping Core. Plans are outlined for continued mentoring of junior P.l.s, and specific approaches for evaluating the progress of the P.I.s. and a plan to specifically guide the P.l.s to RO1 funding is included. Institutional commitment is strong and not dependent on COBRE funding. Plans are also outlined for the recruitment and development of new junior faculty to the institutions and COBRE. The award of this COBRE application would effectively facilitate the continued development of The Center for Stem Cell Biology. This grant also has real promise in expanding our understanding of stem cell plasticity and stem cell transcriptional regulation and developing pre-clinical models for wound healing and muscular dystrophy.