Cellular and Molecular Toxicology Core

项目概要/摘要 阐明抗癌药物诱导正常组织损伤的细胞和分子机制， 药物或电离辐射，由才华横溢的年轻研究人员开发的4个高度创新的研究项目 在华盛顿大学的COBRE中心，研究宿主对癌症治疗的反应。 阿肯色州医学科学（UAMS）。这些研究有助于开发新的机制为基础的 预防或减轻化疗和/或放疗副作用的干预措施。为了实现 这些研究人员将在细胞和分子水平上分析各种组织（体外和体内）。 体内）以确定潜在损伤。由于化学和/或物理制剂的性质、接触途径， 和组织的组成，对损伤的反应是复杂的，变化很大。这一分析要求 昂贵和复杂的仪器，个别实验室负担不起。为了给年轻人提供 调查人员拥有最先进的设备，设施和咨询，否则将是禁止的， 在第1阶段期间建立了细胞和分子毒理学核心（核心B）。在第2阶段，核心B将 继续在Alexei G. Basnakian，MD，PhD，DSc，知名专家 在正常组织损伤和癌症研究领域，一个经验丰富的核心设施主任，和一个成功的COBRE 导师核心主任将监督训练有素的技术人员。在第一阶段，核心证明了 高生产力，同时免费向项目领导人和试点项目受赠人提供服务， 使这个核心在很大程度上自给自足。核心为项目负责人提供各种基本的 和先进的细胞和分子分析化疗和放射诱导的组织损伤，特别是 与DNA断裂相关的不可逆细胞损伤。此外，核心将不断扩大， 现有技术的全部，以满足成员进行的创新研究日益增长的需求 以及UAMS的其他研究人员。具体而言，核心将追求以下目标 具体目标：提供体外和体内功能和结构毒性的灵敏和定量分析 （包括遗传毒性）和测量药物和毒素浓度（目标1）;提供指导、培训、 咨询和技术援助，涉及实验设计、样品制备、分析开发， 数据分析，并为出版物和赠款申请准备高质量的数字，因为它们与 组织损伤的细胞和分子分析（目标2）;并确定和开发新技术， 中心的前沿研究（目标3）。这些目标将极大地有益于 COBRE中心二期的所有4个项目，并丰富了该机构的研究基础设施。

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.