Four highly innovative research projects developed by the talented young investigators of the proposed COBRE Center for Studies of Host Response to Cancer Therapy at the University of Arkansas for Medical Sciences (UAMS) will elucidate the underlying cellular and molecular mechanisms of normal-tissue injury induced by ionizing radiation (IR) for the development of novel mechanism-based interventions to prevent or mitigate the side effects of radiotherapy. To accomplish the goals of their projects, these investigators need to analyze tissue injury at the cellular and molecular levels, particularly in rare populations of adult stem cells in various tissues such as bone marrow hematopoietic stem cells (HSCs), intestinal epithelial stem cells (iESCs), and skin epithelial stem cells (sESCs) because these cells are primarily responsible for tissue repair and regeneration after injury. This analysis requires expensive and sophisticated instrumentation that cannot be afforded by individual laboratories, as well as special expertise that can be obtained only by an individual after receiving extensive training and practice. Therefore, we plan to establish a shared Cellular and Molecular Analytic Core (CMAC) that will operate as a centralized and shared core facility to assist the Project Leaders with their research efforts in the most economic and efficient manner possible. The CMAC is equipped with state-of-the-art instruments. It will be under the leadership of Daohong Zhou, MD, a well-established expert in normal-tissue injury and stem cell research fields, an experienced core facility director, and a successful COBRE mentor; it will be staffed by well-trained technical personnel. The CMAC can provide Project Leaders with various basic and advanced cellular and molecular analyses for IR-induced tissue injury, particularly at the level of tissue stem cells. In addition, the CMAC will constantly expand the repertoire of available techniques to meet the growing needs of the innovative research conducted by members of the COBRE Center, as well as the other investigators at UAMS. Specifically, the CMAC will pursue the following the specific aims: 1) provide mentoring, training, consultation, and technical assistance concerning experimental design, sample preparation, assay development, data analysis, and preparation of high-quality figures for publications and grant applications as they relate to cellular and molecular analysis of tissue injury induced by IR; 2) provide sensitive and quantitative analysis of gene expression, live-cell imaging, and in vitro and in vivo functional assessments of HSCs, iESCs, and sESCs after IR exposure; and 3) identify and develop new technologies to assist in cutting-edge research at the COBRE Center. These objectives will greatly benefit the research proposed in Projects 1, 2, and 3, and impact on Project 4.

Public Health Relevance

The CMAC will provide essential research support services to a group of young COBRE investigators at UAMS to elucidate the underlying cellular and molecular mechanisms of normal-tissue injury induced by ionizing radiation for the development of novel mechanism-based interventions to prevent or mitigate the side effects of radiotherapy. These services will facilitate their career development and enhance scientific innovation and productivity in a cost-efficient manner.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Exploratory Grants (P20)
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Special Emphasis Panel (ZGM1-TWD-A (1C))
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University of Arkansas for Medical Sciences
Little Rock
United States
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