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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Exploratory Grants (P20)
Project #
5P20GM109005-05
Application #
9681444
Study Section
Special Emphasis Panel (ZGM1)
Project Start
Project End
2021-03-31
Budget Start
2019-04-01
Budget End
2020-03-31
Support Year
5
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of Arkansas for Medical Sciences
Department
Type
DUNS #
122452563
City
Little Rock
State
AR
Country
United States
Zip Code
72205
Kiaei, Mahmoud; Balasubramaniam, Meenakshisundaram; Govind Kumar, Vivek et al. (2018) ALS-causing mutations in profilin-1 alter its conformational dynamics: A computational approach to explain propensity for aggregation. Sci Rep 8:13102
Koturbash, Igor (2018) 2017 Michael Fry Award Lecture When DNA is Actually Not a Target: Radiation Epigenetics as a Tool to Understand and Control Cellular Response to Ionizing Radiation. Radiat Res 190:5-11
Luo, Yi; Shao, Lijian; Chang, Jianhui et al. (2018) M1 and M2 macrophages differentially regulate hematopoietic stem cell self-renewal and ex vivo expansion. Blood Adv 2:859-870
Alexander, Tyler C; Simecka, Christy M; Kiffer, Frederico et al. (2018) Changes in cognition and dendritic complexity following intrathecal methotrexate and cytarabine treatment in a juvenile murine model. Behav Brain Res 346:21-28
Liu, Xingui; Wang, Yingying; Zhang, Xuan et al. (2018) Senolytic activity of piperlongumine analogues: Synthesis and biological evaluation. Bioorg Med Chem 26:3925-3938
Nukala, Ujwani; Thakkar, Shraddha; Krager, Kimberly J et al. (2018) Antioxidant Tocols as Radiation Countermeasures (Challenges to be Addressed to Use Tocols as Radiation Countermeasures in Humans). Antioxidants (Basel) 7:
Yadlapalli, Jai Shankar K; Dogra, Navdeep; Walbaum, Anqi W et al. (2018) Pinprick hypo- and hyperalgesia in diabetic rats: Can diet content affect experimental outcome? Neurosci Lett 673:24-27
Nekouei, Mina; Ghezellou, Parviz; Aliahmadi, Atousa et al. (2018) Changes in biophysical characteristics of PFN1 due to mutation causing amyotrophic lateral sclerosis. Metab Brain Dis 33:1975-1984
Cheema, Amrita K; Byrum, Stephanie D; Sharma, Neel Kamal et al. (2018) Proteomic Changes in Mouse Spleen after Radiation-Induced Injury and its Modulation by Gamma-Tocotrienol. Radiat Res 190:449-463
Skinner, Charles M; Miousse, Isabelle R; Ewing, Laura E et al. (2018) Impact of obesity on the toxicity of a multi-ingredient dietary supplement, OxyELITE Pro™ (New Formula), using the novel NZO/HILtJ obese mouse model: Physiological and mechanistic assessments. Food Chem Toxicol 122:21-32

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