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. TABLE OF CONTENTS OVERALL DESCRIPTION 2 OVERALL CENTER CRITIQUE 3 CENTER DIRECTOR 5 OVERALL COMMITTEE BUDGET RECOMMENDATIONS 6 OVERALL ACTION 6 SUPPORT TO BE NEGOTIATED 6 RESEARCH BASE... 6 ADMINISTRATIVE CORE: Yi Zheng, Ph.D ... 10 XENOTRANSPLANT &TRANSGENIC CORE: James Mulloy, PhD, Marie-Dominique Filippi, Ph.D... 11 GENOMICS AND GENETICS CORE: Gregory Grabowsky, MD, Bruce Aronow, PhD ... 14 CELL ANALYSIS AND SORTING CORE: Jose Cancelas, MD, PhD, Claire Chougnet, PharmD, PhD ... 17 TRANSLATIONAL CORE: Punam Malik, MD ... 20 PILOT AND FEASIBILITY (P&F) PROGRAM: Timothy Cripe, M.D., Ph.D. 23

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 #
1P30DK090971-01
Application #
8054038
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
2010-09-30
Budget End
2011-06-30
Support Year
1
Fiscal Year
2010
Total Cost
$714,422
Indirect Cost
Name
Cincinnati Children's Hospital Medical Center
Department
Type
DUNS #
071284913
City
Cincinnati
State
OH
Country
United States
Zip Code
45229
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