The successful application of molecular and cell therapeutics to transplantable hematopoietic cells, including hematopoietic stem cells, holds the promise of life-long cures for inherited diseases of bone marrow-derived cells. The long term goal of the Cincinnati Center of Excellence in Molecular Hematology (CCEMH) is to understand and correct at the molecular level diseases with gene/environmental interactions affecting cells derived from hematopoietic stem cells. We believe that to attain this goal, we must understand basic biological processes that affect lympho-hematopoietic stem cell behavior in vitro and in vivo. We envision this long term goal will be accomplished by inter-disciplinary approaches using state-of-the-art molecular and cell biology methods along with timely and rational use of translational studies in the preclinical and clinical settings. Cincinnati Children's Hospital Medical Center (CCHMC), University of Cincinnati College of Medicine (UC), has developed an intellectual environment that brings together outstanding expertise in virus vector technology, stem cell biology, immune cell biology, basic research in signaling and clinical care in hematology, allergy/immunology and hematopoietic stem cell transplantation. This focus has been greatly strengthened by recruitment of over 50 faculty in these areas in the last 10 years at CCHMC and UC. The areas of basic research are linked by a newly developed and unique Translational Research Initiative, which has facilitated inter-disciplinary interactions and developed an infrastructure that is supporting state-of-the-art trials in cell and gene therapy. Thus, in this application for a new CEMH, we seek to solidify exciting and dramatic growth of research in hematology and related innate immunity/immunology at CCHMC using the shared services and administrative structure of this center grant mechanism. The CCEMH seeks to support a well developed translational research core which complements an outstanding array of basic science cores at CCHMC. These cores are functioning to support innovative research and clinical trials both locally and, in some cases nationally and internationally, in hematology and related immune-based diseases. The relevant cores include a Mouse Xenotransplant/transgenic Core, which maintains specialized mouse strains and provides mouse transplant and transgenic services, a Flow Cytometry Core that includes state-of-the-art hematology flow analysis and sorting capabilities, a Genomics &Genetics Core that support cutting edge genomic analysis of hematologic diseases and normal genetic traits of stem/progenitor cells, and a Translational Core that covers services such as ex vivo manipulation and collection of human cell products, lenti- and retrovirus production, and sophisticated preclinical assay development. Finally, this core grant seeks support for a Pilot/Feasibility program that focuses a highly successful institutional peer-reviewed pilot project initiative into hematologic and related immunologic research and an enhancement program in hosting seminars and annual retreat of the center.

Public Health Relevance

CCHMC provides an outstanding environment to pursue innovative therapies in diseases of the blood and immune system. The CCEMH will provide an essential structure that will allow further coordination in these areas and facilitate new studies, both basic and translational, related to experimental hematology and immunity.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Center Core Grants (P30)
Project #
5P30DK090971-03
Application #
8298260
Study Section
Special Emphasis Panel (ZDK1-GRB-G (O3))
Program Officer
Bishop, Terry Rogers
Project Start
2010-09-30
Project End
2015-06-30
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
3
Fiscal Year
2012
Total Cost
$724,661
Indirect Cost
$240,850
Name
Cincinnati Children's Hospital Medical Center
Department
Type
DUNS #
071284913
City
Cincinnati
State
OH
Country
United States
Zip Code
45229
Rydyznski, Carolyn E; Cranert, Stacey A; Zhou, Julian Q et al. (2018) Affinity Maturation Is Impaired by Natural Killer Cell Suppression of Germinal Centers. Cell Rep 24:3367-3373.e4
Goodman, Michael Aaron; Arumugam, Paritha; Pillis, Devin Marie et al. (2018) Foamy Virus Vector Carries a Strong Insulator in Its Long Terminal Repeat Which Reduces Its Genotoxic Potential. J Virol 92:
Zhang, Cuiping; D'Alessandro, Angelo; Wellendorf, Ashley M et al. (2018) KLF5 controls glutathione metabolism to suppress p190-BCR-ABL+ B-cell lymphoblastic leukemia. Oncotarget 9:29665-29679
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
Rochman, Yrina; Dienger-Stambaugh, Krista; Richgels, Phoebe K et al. (2018) TSLP signaling in CD4+ T cells programs a pathogenic T helper 2 cell state. Sci Signal 11:
Serrano-Lopez, Juana; Nattamai, Kalpana; Pease, Nicholas A et al. (2018) Loss of DEK induces radioresistance of murine restricted hematopoietic progenitors. Exp Hematol 59:40-50.e3
McCauley, Heather A; Chevrier, VĂ©ronique; Birnbaum, Daniel et al. (2017) De-repression of the RAC activator ELMO1 in cancer stem cells drives progression of TGF?-deficient squamous cell carcinoma from transition zones. Elife 6:
Lages, Celine S; Simmons, Julia; Maddox, Avery et al. (2017) The dendritic cell-T helper 17-macrophage axis controls cholangiocyte injury and disease progression in murine and human biliary atresia. Hepatology 65:174-188
Fang, Jing; Bolanos, Lyndsey C; Choi, Kwangmin et al. (2017) Ubiquitination of hnRNPA1 by TRAF6 links chronic innate immune signaling with myelodysplasia. Nat Immunol 18:236-245
Fang, Jing; Bolanos, Lyndsey C; Choi, Kwangmin et al. (2017) Corrigendum: Ubiquitination of hnRNPA1 by TRAF6 links chronic innate immune signaling with myelodysplasia. Nat Immunol 18:474

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