Hematopoietic stem and progenitor cell regulation for enhanced clinical efficacy

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OVERALL CENTER PROJECT SUMMARY The proposed Indiana University School of Medicine (IUSM) Cooperative Center of Excellence in Hematology (CCEH) brings together 25 investigators whose research activities are focused on various aspects of nonmalignant hematology and whose work is highly dependent on one or more of the three biomedical research cores proposed in this application. The central theme of our CCEH 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 transform these findings into translational efforts. The proposed CCEH membership in this application draws from a group of very productive, well-funded and team-oriented investigators with a diverse but complementary experience in hematopoiesis. These experiences include experimental and clinical stem cell transplantation, signaling in and regulation of HSC and HPC, interactions between HSC and the hematopoietic niche, mobilization, homing and engraftment of HSC, modulation of function of freshly isolated cells under different O2 levels, and functional status of HSC after exposure to ionizing radiation. The cores proposed in this CCEH submission evolved from existing shared facilities or cores previously established during the prior funding period and were tailored specifically to meet the current research needs of CCEH members and the general research community nationwide. These include: Experimental Mouse Resources, Flow and Tissue Cytometry, and Hypoxia cores. All cores will support the basic and translational studies that underlie the mission of our CCEH and the community of nonmalignant hematology research at large. These cores will facilitate the development of new discoveries into human trials. 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 CCEH members inside and outside IUSM. Our goal is to establish, maintain, and successfully operate these three state-of-the-art biomedical core facilities and to provide a supportive and enriching environment to foster the growth and development of young and new investigators in nonmalignant hematology. As proposed, the CCEH represents an important assembly of critical cores, infrastructure, and investigators needed to promote and enhance the basic and clinical work in progress in nonmalignant hematology and to provide support that we believe is needed over the next five years.