Harnessing the Power of p53 with Panaxynol from American Ginseng to Suppress Colitis and Prevent Colon Cancer - admin supp

项目总结 炎症性肠病(IBD)是一种慢性疾病，发生结肠癌的风险很高。这 由于复发和缓解的特点，疾病有很高的经济负担。新出现的证据将 肠神经免疫轴与IBD的发生发展巨噬细胞和感觉器官 传入神经在胃肠道系统中非常接近，它们有必要的机械来 相互交流。因此，我们有兴趣针对免疫学和神经学 IBD和相关结肠癌的成分。具体地说，我们想要研究神经免疫相互作用 巨噬细胞和感觉神经之间。人参醇是美国人参中的生物活性成分。 人参、胡萝卜、芹菜和小茴香。人参醇已被证明具有抗炎特性和 神经保护作用，这使它成为一种理想的化合物来检验我们的假设，即人参醇能调节 结肠炎和结肠炎相关结肠癌的神经免疫相互作用。提出了两个目标：1) 确定人参醇对胃肠系统感觉神经的影响，以及2) 检查人参醇是否影响巨噬细胞与感觉神经的相互作用。基于当前的 文献和我们之前使用有条不紊和科学严谨的方案所做的工作，我们假设 人参醇可开发为一种安全、经济有效的抗炎和神经保护剂。 治疗IBD和相关的结肠癌。 该提案中的研究是由Gustavo和他的导师(Murphy博士和Velazquez博士)设计的 考虑到：1)以前的研究和培训，2)额外培训的需要，3)研究潜力，4) 导师对培训的承诺，5)可用的资源，6)职业目标和目的，以及7)公众 拟议研究的健康重要性。墨菲博士(父母资助和导师的MPI)和韦拉兹克斯博士 (导师)将指导古斯塔沃完成研究和培训计划的每一个方面。具体地说，墨菲医生将 提供涉及免疫功能方面的培训，包括巨噬细胞，Velazquez博士将提供 关于人参醇神经保护特性方面的培训。两位导师都将在 天然化合物(人参醇类)研究，以及在结肠炎/癌症模型中。同样重要的是，需要指出的是，戴维斯博士。 墨菲和韦拉兹奎兹处于职业生涯的不同阶段，因此他们的研究领域不仅将相互补充 但他们在专业发展方面的培训也是如此。根据这一奖项，预计古斯塔沃 将：1)在癌症、免疫学和神经科学研究方面实现新的尖端技术培训，2) 发表至少6篇论文，其中至少2篇是第一作者，以及3)成功获得博士后学位 一家顶尖研究机构的研究员职位。精心制定的研究和职业发展培训计划 这一提议将确保实现这些目标。

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 that these goals are reached.