Hematopoietic stem and progenitor cell regulation for enhanced clinical efficacy

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 DESCRIPTION (provided by applicant): The proposed Indiana University School of Medicine (IUSM) Cooperative Hematology Specialized Core Center (CHSCC) brings together 28 investigators whose research activities are focused on various aspects of nonmalignant hematology and whose work is highly dependent on one or more of the four biomedical research cores proposed in this application. The central theme of our CHSCC is the regulation of human and murine hematopoiesis at the level of hematopoietic stem (HSC) and progenitor (HPC) cells. The goal of the investigations of members of this center is to leverage different components of the hematopoietic system to improve the advancement of the clinical utility and efficacy of HSC/HPC-based therapies. We believe that in order to attain these goals, we must understand basic biological processes that affect hematopoietic stem cell behavior both in vitro and in vivo in a basic science laboratory and to eventually establish clinical trials that transfor these findings into translational efforts. The proposed CHSCC membership in this application draws from a group of well-funded investigators with a diverse but complementary experience in experimental and clinical stem cell transplantation, signaling in and regulation of HSC and HPC, developmental emergence of fetal hematopoiesis, gene transfer, interactions between HSC and the hematopoietic niche, mobilization, homing and engraftment of HSC, modulation of function of freshly isolated and ex vivo manipulated HSC, and functional status of HSC after exposure to ionizing radiation. The cores proposed in this CHSCC submission evolved from existing shared facilities and have been adapted to the current needs of this program. These include: Experimental Mouse Resources, Optical Microscopy, Angiogenesis, and Flow Cytometry cores. All cores will support the basic and translational studies that underlie the mission of the CHSCC and will facilitate development of new discoveries into human trials. The program also includes a Pilot and Feasibility Project to be funded in part through Institutional funds in order to enhanc the training of young investigators and enhance their ability to successfully compete for extramural (e.g. NIH) funding. Furthermore, to ensure continued scientific growth and progress, the proposed center has a well-developed enrichment program to advance the development of both young and established CHSCC members. Together, the CHSCC represents an important assembly of critical cores needed to promote and enhance the basic and clinical work in progress and to provide support that we believe is needed over the next five years.