Cellular and Molecular Toxicology Core

细胞和分子毒理学核心

• 批准号: 10025389
• 负责人: Alexei G Basnakian
• 金额: $ 25.84万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-06-24 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10025389
• 关键词: Address; Adverse effects; Analytical Chemistry; Animals; Antineoplastic Agents; Apoptosis; Applications Grants; Arkansas; Autophagocytosis; Biological; Biological Assay; Biomedical Research; Blood; Bone Marrow; Cancer Patient; Cancer Survivor; Cells; Centers of Research Excellence; Chemicals; Chemotherapy and/or radiation; Collaborations; Colorimetry; Comet Assay; Communication; Communities; Complex; Consultations; Core Facility; Country; DNA; DNA Damage; DNA Fragmentation; DNA Nucleotidylexotransferase; DNA Repair; Data Analyses; Deoxyribonucleases; Development; Diagnostic; Disease-Free Survival; Doctor of Philosophy; Economics; Ensure; Enzyme-Linked Immunosorbent Assay; Equipment; Experimental Designs; Faculty; Fee-for-Service Plans; Fees and Charges; Financial Hardship; Fluorescence Microscopy; Goals; Government; Healthcare; Heart; Human Resources; Immune response; Immunohistochemistry; In Situ Hybridization; In Situ Nick-End Labeling; In Vitro; Individual; Injury; Institution; Intervention; Intestines; Ionizing radiation; Kidney; Label; Laboratories; Laboratory Animals; Lead; Leadership; Length; Liquid substance; Liver; Long-Term Effects; Lung; Measurement; Measures; Medical; Mentors; Methods; Molecular; Molecular Analysis; Molecular Toxicology; Nature; Normal tissue morphology; Organ; Outcome; Performance; Pharmaceutical Preparations; Phase; Pilot Projects; Poison; Preparation; Productivity; Publications; Quality of life; Radiation Dose Unit; Radiation therapy; Regimen; Research; Research Infrastructure; Research Personnel; Research Project Grants; Resources; Risk; S Phase; Sampling; Science; Services; Spectral Karyotyping; Spleen; Structure; Talents; Techniques; Testing; Tissues; Toxic effect; Toxicology; Toxin; Training; Treatment-Related Cancer; Universities; Work; anticancer research; assay development; base; burden of illness; cancer therapy; cell injury; cost; design; enzyme activity; experience; exposure route; genotoxicity; in vivo; inflammatory marker; innovation; instrument; instrumentation; mass spectrometer; member; new technology; novel; prevent; programs; radiation-induced tissue damage; response; side effect; small molecule; therapy design; tissue injury; toxicant; training project

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.

项目摘要/摘要 阐明抗癌引起的正常组织损伤的潜在细胞和分子机制 药物或电离辐射，由才华横溢的年轻研究者开发的4个高度创新的研究项目 拟议的第2阶段索布雷研究中心，用于宿主对癌症治疗的宿主反应研究中心 阿肯色州医学科学（UAMS）。这些研究有助于开发基于新机制的新型 预防或减轻化学疗法的副作用的干预措施。实现目标 他们的项目，这些研究者将在细胞和分子水平（体外和IN中）分析各种组织 体内）确定潜在伤害。由于化学和/或物理剂的性质，暴露途径， 组织的组成，对侮辱的反应是复杂的，并且变化很大。该分析需要 单个实验室负担不起的昂贵且精致的仪器。提供初级 使用最先进的设备，设施和咨询的调查人员，否则会令人难以置信 细胞和分子毒理学核心（核心B）是在第1阶段建立的。在第2阶段，核心B将 继续在Alexei G. Basnakian，医学博士，博士，DSC的领导下提供服务， 在正常组织伤害和癌症研究领域，经验丰富的核心设施总监和成功的毛病 导师。核心主任将监督训练有素的技术人员。在第1阶段，核心证明 高生产率，并以免费的费用为项目负责人和试点项目授予者提供服务，但费用收取费用 对于其他用户，这种核心在很大程度上是自给自足的。核心为项目负责人提供了各种基本 以及用于化学疗法和放射诱导的组织损伤的晚期细胞和分子分析，特别是 与DNA碎片相关的不可逆细胞损伤。此外，核心将不断扩展 可用技术的曲目，以满足成员进行的创新研究的不断增长的需求 毛绒中心以及UAMS的其他调查员。具体而言，核心将追求以下 具体目的：对体外和体内功能和结构毒性进行敏感和定量分析 （包括遗传毒性）和药物和毒素浓度的测量（AIM 1）；提供指导，培训， 咨询和有关实验设计，样本准备，测定开发的技术援助， 数据分析以及与出版物的高质量数据和授予应用程序有关 组织损伤的细胞和分子分析（AIM 2）；并确定并开发新技术以协助 中心的尖端研究（AIM 3）。这些目标将极大地受益于提议的研究 第2阶段索布雷中心的所有4个项目以及丰富了该机构的研究基础设施。