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Core E: Experimental Therapeutics Core

核心 E：实验治疗核心

基本信息

批准号：
8933233
负责人：
JAMES E BRADNER
金额：
$ 16.5万
依托单位：
DANA-FARBER CANCER INST
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-04-15 至 2020-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8933233
关键词：
Acute Graft Versus Host Disease Address Allogenic Analytical Chemistry Antibodies Antigens B-Lymphocytes Bacteria Biochemical Biochemistry and Cellular Biology Biological Biological Markers Biological Models Biology Cell physiology Cells Characteristics Chemicals Chromatin Chronic Clinical Clinical Research Clinical assessments Collaborations Computational Biology Development Disease Drug effect disorder Epigenetic Process Fibrosis Goals Histocompatibility Testing Histones Human Immune Immunoglobulins Immunology Inflammation Inflammatory Response Insecta Interdisciplinary Study Laboratories Leadership Mass Spectrum Analysis Methods Modeling Molecular Morbidity - disease rate Organic Chemistry Organic Synthesis Pathway interactions Patients Peptide Synthesis Peptides Pharmaceutical Preparations Pharmacologic Substance Pharmacology Phase Pre-Clinical Model Prevention Production Proteins Reader Reagent Recombinant Proteins Research Research Infrastructure Research Personnel S Phase Series Signal Pathway Signal Transduction Solid Surface Antigens Technology Tertiary Protein Structure Testing Therapeutic Therapeutic Agents Therapeutic Intervention Toxic effect Translational Research Translations Validation Yeasts base chronic graft versus host disease clinical investigation clinical practice graft vs host disease hematopoietic cell transplantation in vivo inhibitor/antagonist innovation insight interdisciplinary approach mortality novel novel therapeutics pre-clinical programs prototype response small molecule synthetic peptide tool translational study treatment strategy

项目摘要

Project Summary Core E The discovery, characterization and development of novel therapeutic strategies to ameliorate the morbidity and mortality of graft-versus-host disease (GVHD) requires an interdisciplinary approach leveraging emerging biological insights and novel pharmacologic strategies. Already, this Program has successfully developed new and effective therapeutic interventions based on biological hypotheses tested in preclinical models of GVHD. To accelerate the pace of research and to more immediately connect the preclinical and clinical programs, we have created a new Experimental Therapeutics Core Laboratory. The goals of the Core are (a) to provide immediate and unrestricted access to chemical probes, investigational agents and therapeutic substances for preclinical and biological assessment, (b) to derive chemical derivatives of active agents to address disclosed pharmacologic liabilities encountered in this research, as needed, (c) to provide high-purity synthetic peptides allowing the validation of surface antigens and (d) to purify recombinant proteins or protein domains for the characterization of putative alloreactive antibodies. Beyond these technical objectives, the leadership and staff of the Experimental Therapeutics Core Laboratory will provide expertise in molecular pharmacology guiding selection and use of chemical tools alone or in combination in biological and translational studies proposed herein. As therapeutic agents enter human clinical investigation, the Core will contribute to the selection and assessment of clinical biomarkers of drug action. The completion of these objectives will require the development of new methods in organic synthesis, parallel solid-phase peptide synthesis, analytical chemistry, protein production and mass spectrometry. As such, the Core is located in a state-of-the-art chemical biology laboratory which possesses the infrastructure, expertise and technology required to complete the stated Aims and to integrate inter-programmatic activities.

项目摘要核心E 发现、表征和开发新的治疗策略以改善发病率移植物抗宿主病（GVHD）的发病率和死亡率需要一种跨学科的方法，生物学见解和新的药理学策略。目前，该项目已成功开发出新的以及基于在GVHD临床前模型中测试的生物学假设的有效治疗干预。为了加快研究的步伐，并更直接地连接临床前和临床项目，我们创建了一个新的实验治疗学核心实验室。核心的目标是：（a）提供立即和不受限制地获得化学探针、研究试剂和治疗物质，临床前和生物学评估，（B）衍生活性剂的化学衍生物以解决所公开的根据需要，（c）提供高纯度的合成肽允许表面抗原的验证，和（d）纯化重组蛋白或蛋白结构域，推定的同种异体反应性抗体的表征。除了这些技术目标，领导层和工作人员实验治疗学核心实验室将提供分子药理学指导方面的专业知识在生物学和转化研究中单独或组合选择和使用化学工具本文所随着治疗药物进入人类临床研究，核心将有助于选择和评估药物作用的临床生物标志物。要实现这些目标，有机合成、平行固相肽合成、分析化学、蛋白质生产和质谱分析。因此，核心位于最先进的化学生物学拥有完成所述目标所需的基础设施、专业知识和技术的实验室并整合方案间活动。