This proposal requests support for a predoctoral and postdoctoral Training Program in Pediatric Hematologic and Oncologic Diseases in the Cincinnati Children's Hospital Medical Center (CCHMC), University of Cincinnati College of Medicine. The underlying premise of this Training Program is that there is a recognition of and need to address the lack of individuals trained in therapeutic research on pediatric hematologic and oncologic diseases who also have a deep appreciation for taking scientific discovery into the clinic. Therefore, the goal of the Training Program is to provide a rigorous understanding of the basic mechanisms of pediatric hematologic and oncologic diseases with a clear translational focus. The program draws heavily upon integrated, m ultidisciplinary, innovative, and established graduate progr ams, Ph.D. postodoctoral training programs, and clinical fellowship training programs from 7 divisions within CCHMC, and involves 21 NIH funded basic scientists and physician-scientists as core mentoring faculty and 5 ancillary clinical faculty. This program enrolls promising young doctoral and postdoctoral (2 predoctoral and 4 postdoctoral) candidates, with a emphasis on minority candidate recruitment, to specialize on one of the hematology and oncology research areas under the direct mentorship of a core mentoring faculty and an ancillary clinical faculty. The areas of research include pediatric hematologic diseases such as leukemia, Fanconi anemia, myeloproliferative disorders, coagulation disorders, and sickle cell disease, immuno- deficiency disorders such as X-linked lymphoproliferative disorder, severe combined immunodeficiencies, Wiskott-Aldrich syndrome, and common variable immunodeficiency, molecular gene therapy strategies treating Fanconi anemia, storage diseases, and sickle cell anemia, and targeted therapies against childhood cancers such as leukemia/lymphoma, neuroblastoma, sarcomas, and musculoskeletal tumors. The selected program faculty share research interests and have a history of collaboration in studies of various blood- related research activities, yet they approach hematologic and oncologic diseases and therapeutics from different perspectives. The use of mouse models combined with patient-directed initiatives represents one of the unique strengths of the Training Program. The grant will include an administrative core consisting of the Principal Investigator, Co-Pi, an Executive Committee, an Admission Committee, an Advisory Committee, and an External Advisory Committee. Training will combine a series of required curriculum including an ethical education course, Experimental Hematology, Immunological Mechanisms of Diseases, Action of Cancer Therapeutics, and Translational Trial Development and Support Laboratory Educational Activities, as well as a number of electives including Biostatistics, Clinical Trials, Functional Genomics, and Seminar in Drug Development. Regular research retreats, data clubs, journal clubs, and seminar series will serve to complement the mentor-directed research activities by further enhancing the knowled ge base of the trainees and cohesiveness of the program. The progress of each trainee will be reviewed and evaluated semi- annually.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Institutional National Research Service Award (T32)
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NHLBI Institutional Training Mechanism Review Committee (NITM)
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Chang, Henry
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Cincinnati Children's Hospital Medical Center
United States
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Du, Wei; Liu, Wei; Mizukawa, Benjamin et al. (2018) A non-myeloablative conditioning approach for long-term engraftment of human and mouse hematopoietic stem cells. Leukemia 32:2041-2046
Du, Wei; Li, Xiaoli; Wilson, Andrew F et al. (2018) A small molecule p53 activator attenuates Fanconi anemia leukemic stem cell proliferation. Stem Cell Res Ther 9:145
Li, Xiaoli; Wilson, Andrew F; Du, Wei et al. (2018) Cell-Cycle-Specific Function of p53 in Fanconi Anemia Hematopoietic Stem and Progenitor Cell Proliferation. Stem Cell Reports 10:339-346
Zhang, Tingting; Du, Wei; Wilson, Andrew F et al. (2017) Fancd2 in vivo interaction network reveals a non-canonical role in mitochondrial function. Sci Rep 7:45626
Du, Wei; Amarachintha, Surya; Wilson, Andrew F et al. (2016) SCO2 Mediates Oxidative Stress-Induced Glycolysis to Oxidative Phosphorylation Switch in Hematopoietic Stem Cells. Stem Cells 34:960-71
Du, Wei; Amarachintha, Surya; Wilson, Andrew F et al. (2016) Hyper-active non-homologous end joining selects for synthetic lethality resistant and pathological Fanconi anemia hematopoietic stem and progenitor cells. Sci Rep 6:22167
Zhang, Tingting; Wilson, Andrew F; Mahmood Ali, Abdullah et al. (2015) Loss of Faap20 Causes Hematopoietic Stem and Progenitor Cell Depletion in Mice Under Genotoxic Stress. Stem Cells 33:2320-30
Li, Xiaoli; Li, Jie; Wilson, Andrew et al. (2015) Fancd2 is required for nuclear retention of Foxo3a in hematopoietic stem cell maintenance. J Biol Chem 290:2715-27
Du, Wei; Amarachintha, Surya; Erden, Ozlem et al. (2015) Fancb deficiency impairs hematopoietic stem cell function. Sci Rep 5:18127
Amarachintha, Surya; Sertorio, Mathieu; Wilson, Andrew et al. (2015) Fanconi Anemia Mesenchymal Stromal Cells-Derived Glycerophospholipids Skew Hematopoietic Stem Cell Differentiation Through Toll-Like Receptor Signaling. Stem Cells 33:3382-96

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