PROJECT SUMMARY Inflammatory Bowel Disease (IBD) is a chronic condition with a high risk for development of colon cancer. This illness has a high financial burden due to its relapsing and remitting features. Emerging evidence links the intestinal neuro-immune axis to the development and progression of IBD. Both macrophages and sensory afferent nerves are in close proximity in the gastrointestinal system, and they have the machinery necessary to communicate with one another. Thus, we are interested in targeting the immunological and neurological components of IBD and associated colon cancer. Specifically, we want to study the neuro-immune interactions between macrophages and sensory afferent nerves. Panaxynol is a bioactive component of American Ginseng, carrots, celery, and fennel. Panaxynol has been shown to exhibit anti-inflammatory properties and neuroprotective effects, which make it an ideal compound to test our hypothesis that panaxynol can modulate neuro-immune interactions in colitis and colitis-associated colon cancer. Two aims are proposed: 1) To determine the impact of panaxynol on sensory afferent nerves in the gastrointestinal system, and 2) To examine whether panaxynol influences macrophage interactions with sensory nerves. Based on the current literature and our previous work using methodical and scientifically rigorous protocols, we hypothesize that panaxynol can be developed as a safe, cost-effective anti-inflammatory and neuro-protective agent to be used for IBD and associated colon cancer. The studies in this proposal were designed by Gustavo and his Mentors (Drs. Murphy and Velazquez) taking into consideration: 1) previous research and training, 2) need for additional training, 3) research potential, 4) mentors’ commitment to training, 5) available resources, 6) career goals and objectives, and 7) the public health importance of the proposed research. Drs. Murphy (MPI on parent grant and Mentor) and Dr. Velazquez (Mentor) will guide Gustavo through each aspect of the research and training plan. Specifically, Dr. Murphy will provide training in aspects that involve immune function including macrophages and Dr. Velazquez will provide training in aspects involving neuro-protective properties of panaxynol. Both mentors will provide guidance in natural compound (panaxynol) research, and in colitis/cancer models. It also is important to point out that Drs. Murphy and Velazquez are at different stages of their careers so not only will their research areas complement each other but so will their training in professional development. Under this award it is expected that Gustavo will: 1) achieve new training in cutting edge techniques in cancer, immunology, and neuroscience research, 2) publish at least 6 papers with a minimum of 2 as first author, and 3) be successful in attaining a post-doctoral fellow position at a top-notch research institute. The elaborate research and career development training plan that is proposed will ensure t...