Transducible Molecular Probes for Imaging Tumors

应聘者：克劳德·瑟林博士，医学博士，放射学助理教授，在临床影像和影像研究方面有很强的背景。他的长期职业目标是成为一名临床科学家和独立调查员，开发新的成像探针，以改进对人类肿瘤的非侵入性检测和表征。他的近期目标是在分子生物学和小动物成像方面进行一段时间的高强度科学培训和发展。他设计了一个分阶段的职业发展计划，强调实践研究，但也包括课程工作和其他有组织的教学活动。 环境：加州大学圣地亚哥分校丰富的跨学科环境是求职者短期和长期成功的理想选择。瑟林博士将得到史蒂文·道迪博士的指导，他是一位成就卓著的分子生物学家和霍华德·休斯研究员，他对利用蛋白质转导来开发用于肿瘤治疗的新型分子探测器产生了浓厚的兴趣。瑟林博士将把这项技术用于成像。候选人还将得到罗伯特·马特里博士的指导，他是一位在造影剂和小动物成像方面拥有专业知识的成功的临床成像科学家，也是P20拨款的首席研究员，该基金旨在加州大学圣迭戈分校开发活体细胞和分子成像中心。通过这两位导师，Sirlin博士还将有机会与加州大学圣地亚哥分校医学院及其附属机构的其他杰出研究人员建立大量联系和长期合作。加州大学圣迭戈分校拥有西林博士实现目标所需的所有研究和成像资源。 研究：细胞和分子过程成像是诊断成像的新天地。Sirlin博士将专注于将蛋白质转导作为一种强大的解决方案，以解决许多细胞内靶向范例的药物传递限制。他将构建由一个或多个蛋白质转导结构域组成的分子探针，用于细胞内递送，靶向结构域将探针捕获在感兴趣的细胞中，以及三种不同的成像报告，以允许对活体小鼠的肿瘤进行正电子发射计算机断层扫描、闪烁成像和磁共振成像。药物将在体外进行测试和优化，然后在体内进行测试。Sirlin博士提出的研究融合了分子生物学、报告探针设计、合成化学、动物肿瘤模型和多模式小动物成像的不同方面，因此与他的培养目标非常吻合，并为他的职业发展提供了合理的机制。

DESCRIPTION (provided by applicant): Candidate: Dr. Claude Sirlin, M.D., is an assistant professor in radiology with a strong background in clinical imaging and imaging research. His long-term career goal is to become a clinical scientist and independent investigator developing novel imaging probes to improve the non-invasive detection and characterization of human tumors. His immediate objective is to pursue an intense period of scientific training and development in molecular biology and small animal imaging. He has designed a phased career development plan that emphasizes hands-on research but also incorporates course work and other structured didactic learning activities. Environment: The rich and interdisciplinary environment at the University of California, San Diego is ideal for the candidate's short- and long-term success. Dr. Sirlin will be mentored by Dr. Steven Dowdy, Ph.D., an accomplished molecular biologist and Howard Hughes investigator who has developed a focused interest in using protein transduction to develop novel molecular probes for tumor therapy. Dr. Sirlin will adapt this technology for imaging. The candidate will also be mentored by Dr. Robert Mattrey, M.D., a successful clinical imaging scientist with expertise in contrast media and small animal imaging who is the principal investigator on a P20 grant aimed at developing an In Vivo Cellular and Molecular Imaging Center at UCSD. Through both of his mentors, Dr. Sirlin will also have the opportunity to form numerous contacts and long-term collaborations with other outstanding investigators in the UCSD School of Medicine and affiliated institutes. UCSD has all the necessary research and imaging resources for Dr. Sirlin to accomplish his goals. Research: Imaging cellular and molecular processes is the new horizon for diagnostic imaging. Dr. Sirlin will focus on protein transduction as a powerful solution to drug delivery limitations for many intracellular targeting paradigms. He will construct molecular probes consisting of one or more protein transduction domains for intracellular delivery, targeting domains to trap the probes in the cells of interest, and three different imaging reporters to permit PET, scintigraphic, and MR imaging of tumors in live mice. Agents will be tested and optimized in vitro and then tested in vivo. Dr. Sirlin's proposed research integrates different aspects of molecular biology, reporter probe design, synthetic chemistry, animal tumor models, and multimodality small animal imaging and therefore provides a good fit with his training objectives and serves as logical mechanism for his career development.