Validation of an Intraoperative Neuro-Monitoring Contrast Agent for Cranial Nerves

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Project Summary Due to a lack of tools and new alternatives, the identification of molecular hallmarks of prostate cancer is limited to biopsy detection, usually motivated by high expression of prostate-specific antigen. However, sodium channels appear to present an alternative medium through which prostate cancer can be tracked. In the current research, I plan to interrogate models of prostate cancer, use a venom peptide to investigate NaV1.7 and develop a deep understanding of prostate tumor biology. The ultimate goal of this proposal is to acquire the necessary skills to launch a competitive, independent research career in the field of molecular fluorescence/PDT imaging and treatment, specializing in prostate cancer research. My long-term career goal is to lead a team of researchers (that includes underrepresented students) primarily interested in using synthetic methodologies and developing sensor- driven technologies to identify prostate cancer — approaches that once developed will apply to other diseases. Building on my background in synthetic chemistry and my extensive experience developing fluorescent/PET probe platforms, the research plan centers on the development of a multi-modal theranostic agent comprised of a bio-active venom peptide, a light-driven system that has the potential to target sodium channel NaV1.7 to track prostate cancer cells. Taken together, the next subsequent steps are to use the newly developed theranostic agent in fluorescent imaging and photodynamic therapy of prostate cancer tumors in vivo. Once I develop these technologies with a novel probe platform, I will be uniquely suited to perform in vivo fluorescent/PDT experiments with prostate cancer. The proposal will test my hypothesis that natural venom peptides combined to a sensor can inform a fantastic approach and a reliable theranostic agent to aid in the identification of prostate cancer in vivo via the tracking of sodium channels. Necessary to the success of the K99 phase is the guidance and mentoring of world-class leaders: Dr. Thomas Reiner, leader in the development of nuclear imaging probes and strategies to investigate lung and brain cancers and recently the peripheral nervous system, and Dr. Glenn King, an internationally renowned expert in venom elucidation with a focus on chronic pain, epilepsy and brain stroke. The proposed project will undoubtedly expand to other physiochemically active peptides applicable to other clinically relevant conditions, such as sports injuries, domestic assaults, cancer survivors and blast injuries in warfighters.