Designer Molecular Probes for Biomedical Applications

项目摘要/摘要： PI是宾夕法尼亚大学(UPenn)的化学教授，2003年他在那里 启动了一项多学科研究计划，开发分子探测器，导致 在化学生物学、放射学、细胞基因组学/转录组学和 麻醉学。在这项研究的过程中，国际和平研究所指导了8名博士后研究员，25名 研究生和40名本科生，其中许多人获得了国家奖项，大多数人 毕业生追求科学和生物医学方面的职业。PI的研究借鉴了正式的 超分子有机化学(哈佛-美因茨)、生物无机和生物物理培训 化学(加州理工，博士)和生物学/生物分子成像(加州理工，博士后)。少年派的 在过去的15年里，沉浸在宾夕法尼亚大学的生物医学研究企业中已经变得更加光鲜 这段经历。通过关键的合作，PI已经解决了重大的生物医学研究 问题，使用化学合成、蛋白质化学和生物分析化学的工具。 该协会的85份同行评议出版物、6项专利、2本编辑书籍和投稿书籍 各章重点介绍了生产力、创新、影响和传播在 生物医学研究中化学工具的开发与应用。私家侦探的服务 确认对科学教育、外展、社区建设和青少年的坚定承诺 教职员工指导。这项米拉奖将延长PI非常成功的通用汽车资助的研究 在三个项目领域：1)使用氙基核磁共振造影剂的分子成像；2) 细胞转录组的体内分析和光激活的mRNA调控 寡核苷酸探针；以及，3)阐明全麻药-蛋白质与新的 荧光探针、超灵敏的129Xe核磁共振波谱和其他生物物理方法。 下一个五年计划的重要目标是改进这些基于探测器的技术 世界级研究-宾夕法尼亚大学的合作者建立了高价值的探测器，可以 广泛传播给生物医学研究界。总而言之，这些工具将 促进我们对正常生物/生物医学过程的分子理解(包括 全身麻醉)，并为改善诊断和治疗许多 人类疾病，包括癌症、神经变性和糖尿病。

Project Summary/Abstract: The PI is a Professor of Chemistry at the University of Pennsylvania (UPenn), where in 2003 he launched a multidisciplinary research program developing molecular probes that have led to breakthroughs in Chemical Biology, Radiology, Cellular Genomics/Transcriptomics, and Anesthesiology. In the course of this research, the PI has mentored 8 postdoctoral fellows, 25 graduate students, and 40 undergraduates, with many winning national awards and most graduates pursuing careers in science and biomedicine. The PI's research draws on formal training in supramolecular organic chemistry (Harvard-Mainz), bioinorganic and biophysical chemistry (Caltech, Ph.D.), and biology/biomolecular imaging (Caltech, postdoc). The PI's immersion for the past 15 years in the biomedical research enterprise at UPenn has burnished this experience. Through key collaborations, the PI has tackled significant biomedical research questions, using the tools of chemical synthesis, protein chemistry, and bioanalytical chemistry. The PI's 85 peer-reviewed publications, 6 patents, 2 edited books and contributed book chapters highlight a track record of productivity, innovation, impact, and dissemination in the development and application of chemical tools for biomedical research. The PI's service confirms a strong commitment to science education, outreach, community building, and junior faculty mentoring. This MIRA award will extend the PI's highly successful GM-funded research in three program areas: 1) molecular imaging using xenon-based MRI contrast agents; 2) cellular transcriptome-in-vivo-analysis and mRNA regulation using light-activated oligonucleotide probes; and, 3) elucidation of general anesthetic-protein interactions with novel fluorescent probes, ultrasensitive 129Xe NMR spectroscopy, and other biophysical methods. Significant goals of the next five-year period are to refine these probe-based technologies with world-class research-collaborators at UPenn and establish high-value probes that can be disseminated broadly to the biomedical research community. Collectively, these tools will advance our molecular understanding of normal biological/biomedical processes (including general anesthesia), and provide avenues for improved diagnosis and treatment of many human diseases, including cancer, neurodegeneration, and diabetes.