Core E: Experimental Therapeutics Core

项目摘要核心E 改善发病率的新治疗策略的发现、特征和发展 移植物抗宿主病(GVHD)的死亡率需要一个跨学科的方法，利用新出现的 生物学见解和新的药理策略。该计划已经成功地开发了新的 以及基于在GVHD临床前模型中检验的生物学假设的有效治疗干预。 为了加快研究的步伐，并更快地将临床前和临床计划联系起来，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)衍生活性物质的化学衍生物，以解决所披露的问题 在本研究中遇到的药理责任，根据需要，(C)提供高纯度合成肽 允许验证表面抗原和(D)纯化重组蛋白或蛋白结构域以用于 推测的同种异体反应抗体的特征。除了这些技术目标之外，领导层和工作人员 将提供分子药理学指导方面的专业知识 建议在生物和翻译研究中单独或结合使用化学工具 在这里。随着治疗药物进入人类临床研究，核心将有助于选择和 评价药物作用的临床生物标志物。完成这些目标将需要 有机合成、平行固相多肽合成、分析化学新方法的发展 蛋白质生产和质谱学。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 以及整合方案间活动。

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.