Transducible Molecular Probes for Imaging Tumors

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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.