Designer Molecular Probes for Biomedical Applications

项目概要/摘要： PI是宾夕法尼亚大学（UPenn）的化学教授，2003年， 启动了一项多学科研究计划，开发分子探针， 化学生物学、放射学、细胞基因组学/转录组学的突破， 麻醉科。在这项研究的过程中，PI指导了8名博士后研究员，25名 研究生和40名本科生，其中许多人获得国家奖项， 追求科学和生物医学事业的毕业生。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（加州理工学院，博士），和生物学/生物分子成像（加州理工学院，博士后）。PI的 在过去的15年里，在宾夕法尼亚大学的生物医学研究企业中， 这段经历通过重要的合作，PI已经解决了重要的生物医学研究 问题，使用化学合成，蛋白质化学和生物分析化学的工具。 PI的85篇同行评审出版物，6项专利，2本编辑书籍和贡献书籍 章节强调了生产力，创新，影响和传播的跟踪记录， 生物医学研究化学工具的开发和应用。PI的服务 确认了对科学教育，外展，社区建设和初级教育的坚定承诺。 教师指导。这MIRA奖将扩大PI的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MRI造影剂的分子成像; 2） 细胞转录组在体内分析和mRNA调控使用光激活 寡核苷酸探针;和，3）阐明全身麻醉剂-蛋白质相互作用与新的 荧光探针、超灵敏的129 NMR光谱和其他生物物理方法。 下一个五年期的重要目标是改进这些基于探针的技术， 世界级的研究合作者在宾夕法尼亚大学，并建立高价值的探针，可以 广泛传播到生物医学研究界。总的来说，这些工具将 推进我们对正常生物/生物医学过程的分子理解（包括 全身麻醉），并提供了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.