Cellular and Molecular Toxicology Core

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PROJECT SUMMARY/ABSTRACT To elucidate the underlying cellular and molecular mechanisms of normal-tissue injury induced by anticancer drugs or ionizing radiation, 4 highly innovative research projects developed by the talented young investigators of the proposed Phase 2 COBRE Center for Studies of Host Response to Cancer Therapy at the University of Arkansas for Medical Sciences (UAMS). These studies contribute to the development of novel mechanism-based interventions to prevent or mitigate the side effects of chemo- and/or radiotherapy. To accomplish the goals of their projects, these investigators will analyze various tissues at the cellular and molecular levels (in vitro and in vivo) to determine potential injury. Due to the nature of the chemical and/or physical agent, route of exposure, and the composition of the tissue, the response to the insult is complex and varies widely. This analysis requires expensive and sophisticated instrumentation that individual laboratories cannot afford. To provide junior investigators with state-of-the-art equipment, facilities, and consultation that would otherwise be prohibitive, the Cellular and Molecular Toxicology Core (Core B) was established during Phase 1. In Phase 2, Core B will continue to offer services under the leadership of Alexei G. Basnakian, MD, PhD, DSc, a well-established expert in normal-tissue injury and cancer research fields, an experienced core facility director, and a successful COBRE mentor. The core director will oversee well-trained technical personnel. During Phase 1, the core demonstrated high productivity, and while offering services to project leaders and pilot project grantees at no cost, fees charged to other users have made this core largely self-sufficient. The core provides project leaders with various basic and advanced cellular and molecular analyses for chemotherapy- and radiation-induced tissue injury, particularly irreversible cell injury associated with DNA fragmentation. In addition, the core 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 other investigators at UAMS. Specifically, the core will pursue the following specific aims: provide sensitive and quantitative analysis of in vitro and in vivo functional and structural toxicity (including genotoxicity) and measurements of drug and toxin concentrations (Aim 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 (Aim 2); and identify and develop new technologies to assist in the cutting-edge research of the Center (Aim 3). These objectives will greatly benefit the research proposed in all 4 projects of the Phase 2 COBRE Center as well as enrich the research infrastructure of the institution.