This new NIDDK P30 proposal seeks to establish a Center of Excellence in Hematology at the joint campuses of the University of Pennsylvania (UPENN) and the Children's Hospital of Philadelphia (CHOP) We believe that research and education in the field of benign hematology has achieved a critical mass a UPENN/CHOP. The 13 Investigators of this proposal are well funded by the NIH and published and have multiple co-authored papers and grants. Recent investigator driven enhancements in our research and clinical infrastructures include establishing: a) a Human Embryonic Stem Cell Center (2008);b) an overarching Blood Center focused on enhancing "bench-to-bedside" research in benign hematology (2009);and c) have recruited two new highly regarded investigators to establish a Comprehensive Adult and Pediatric Bone Marrow Failure Program to coordinate patient care as well as basic and translational research. Our educational efforts are supported by two major NIH training grants: An NIDDK benign hematopoiesis T32 and a NHLBI K12 award on benign hematology. As the number of UPENN/CHOP hematology investigators, research projects, clinical programs and trainees expand, it becomes increasingly important to focus our efforts into a cohesive, synergistic whole. To address this need, the current application seeks support to establish and maintain a multi-investigator, collaborative program on benign human hematopoiesis and associated diseases. Scientific efforts will involve three intertwined foci: 1) advancing our understanding of normal hematopoiesis and of BMF syndromes, 2) using such knowledge to develop novel therapeutic approaches for the hemoglobinopathies and BMF syndromes, as well as 3) using the knowledge gained under (1) to develop novel cellular-based therapeutics for the treatment of hematologic disorders. We believe that this propitious P30 RFA offers the opportunity to exploit and enhance our current strengths in benign hematology. Accordingly, we seek to develop an organized hematopoiesis program that will provide centralized state-of-the-art core facility technical support, offer pilot programs to attract young investigators and organize educational events. We anticipate that 5 years of such support will enhance our productivity as evidenced by important publications in the area of benign hematopoiesis, more synergistic research efforts, growth in the number of faculty and fellows focused on relevant areas and a further increase in our NIH-based funding, particularly multi-investigator grants.
This proposal is to support on-going efforts in our group in understanding how the bone marrow makes blood and use this knowledge to treat a number of blood diseases as well as use this same knowledge to develop new strategies for delivering care for a wide number of diseases (cellular therapeutics). The proposal is not only to gain additional support for key research cores in the area of making blood, but also to use this to bring the various research efforts on campus into a cohesive whole.
|Wunderlich, Mark; Brooks, Ryan A; Panchal, Rushi et al. (2014) OKT3 prevents xenogeneic GVHD and allows reliable xenograft initiation from unfractionated human hematopoietic tissues. Blood 123:e134-44|
|Sullivan, Spencer K; Mills, Jason A; Koukouritaki, Sevasti B et al. (2014) High-level transgene expression in induced pluripotent stem cell-derived megakaryocytes: correction of Glanzmann thrombasthenia. Blood 123:753-7|
|Kamat, Viraj; Paluru, Prasuna; Myint, Melissa et al. (2014) MicroRNA screen of human embryonic stem cell differentiation reveals miR-105 as an enhancer of megakaryopoiesis from adult CD34+ cells. Stem Cells 32:1337-46|
|Thom, Christopher S; Traxler, Elizabeth A; Khandros, Eugene et al. (2014) Trim58 degrades Dynein and regulates terminal erythropoiesis. Dev Cell 30:688-700|
|Paralkar, Vikram R; Mishra, Tejaswini; Luan, Jing et al. (2014) Lineage and species-specific long noncoding RNAs during erythro-megakaryocytic development. Blood 123:1927-37|
|Shin, Jae-Won; Buxboim, Amnon; Spinler, Kyle R et al. (2014) Contractile forces sustain and polarize hematopoiesis from stem and progenitor cells. Cell Stem Cell 14:81-93|
|Paluru, Prasuna; Hudock, Kristin M; Cheng, Xin et al. (2014) The negative impact of Wnt signaling on megakaryocyte and primitive erythroid progenitors derived from human embryonic stem cells. Stem Cell Res 12:441-51|
|Tiyaboonchai, Amita; Mac, Helen; Shamsedeen, Razveen et al. (2014) Utilization of the AAVS1 safe harbor locus for hematopoietic specific transgene expression and gene knockdown in human ES cells. Stem Cell Res 12:630-7|
|Crispino, John D; Weiss, Mitchell J (2014) Erythro-megakaryocytic transcription factors associated with hereditary anemia. Blood 123:3080-8|
|Buxboim, Amnon; Swift, Joe; Irianto, Jerome et al. (2014) Matrix elasticity regulates lamin-A,C phosphorylation and turnover with feedback to actomyosin. Curr Biol 24:1909-17|
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