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，他于 2003 年在该校 启动了一项开发分子探针的多学科研究计划，该计划导致 化学生物学、放射学、细胞基因组学/转录组学等领域的突破 麻醉学。在本研究过程中，PI指导了8名博士后，25名 研究生、本科生40名，其中有多人获国家级奖项，其中多位获国家级奖项。 从事科学和生物医学职业的毕业生。 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 过去 15 年在宾夕法尼亚大学生物医学研究事业中的浸淫已得到磨练 这次经历。通过重要的合作，PI 已经完成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 发表的 85 篇同行评审出版物、6 项专利、2 本编辑书籍和贡献书籍 各章重点介绍了生产力、创新、影响和传播的记录 生物医学研究化学工具的开发和应用。 PI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 师资辅导。 MIRA 奖项将延续 PI 非常成功的 GM 资助的研究成果 三个项目领域：1）使用基于氙的 MRI 造影剂进行分子成像； 2） 使用光激活的细胞体内转录组分析和 mRNA 调控 寡核苷酸探针；以及，3) 阐明全身麻醉剂与新型药物的蛋白质相互作用 荧光探针、超灵敏 129Xe NMR 光谱和其他生物物理方法。 下一个五年的重要目标是完善这些基于探针的技术 宾夕法尼亚大学的世界级研究合作者，并建立了高价值的探针，可以 广泛传播给生物医学研究界。总的来说，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），并为改善许多疾病的诊断和治疗提供途径 人类疾病，包括癌症、神经退行性疾病和糖尿病。

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.