Bioflavonoid apigenin induces phosphorylation of p53

描述(由申请人提供)：本申请是由Rukiyah Van Dross博士(首席调查员)和Jill C.Pling博士(赞助人)提交的，旨在为代表不足的少数族裔颁发K01导师职业发展奖。申请包括两个阶段的职业发展：第一阶段(指导，依赖)将包括为期两年的持续博士后指导范德罗斯博士由佩林博士和第二阶段(指导，独立)包括三年的继续研究，范德罗斯博士以一种更独立的方式在病理学和实验室医学系担任研究助理教授，但仍在毗邻佩林博士的研究实验室的空间工作，由佩林博士继续指导。在第一阶段，范·德罗斯博士将在佩林博士的实验室担任博士后研究员，继续在实验设计、数据解释、手稿/赠款撰写、研究生/技术人员监督、参加科学会议以及发展与癌症发生和化学预防领域的同事的联系方面发展独立的研究技能，目的是建立未来的研究合作，并发展一个可以为范·德罗斯博士提供建议的该领域同事网络。Van Dross博士将在其职业发展计划的第一阶段进行的研究项目在本申请中详细介绍，重点是研究p38 MAP激酶在生物黄酮类芹菜素调节化学预防作用中的作用。这项研究项目是由范德罗斯博士与佩林博士共同开发的，其目标显然与癌症生物学和化学预防有关。Van Dross博士提出的实验方法将扩展她对芹菜素诱导p38 MAP激酶以及伴随而来的P53蛋白磷酸化和细胞凋亡的初步观察。在这项K01申请中提出的研究与佩林博士的NIH资助CA72987-05是分开的，该资助题为“芹菜素化学预防的分子机制”，其重点是芹菜素诱导ERK和翻译后修饰后对P53的下游影响。在职业发展计划的第二阶段，Van Dross博士将被提升为病理学和实验室医学系的研究助理教授(见主席信)，假设继续提高生产率，实现K01拨款的研究目标。在第二阶段，范·德罗斯博士将继续接受佩林博士在她的研究以及拨款撰写技能、手稿写作、期刊文章评论和她所在领域的专业联系方面的指导。Van Dross博士在其职业发展计划的第二阶段进行的研究在本申请中详细介绍，并将重点研究p38 MAPK和P53的蛋白质/蛋白质相互作用及其在细胞凋亡中的作用。范德罗斯博士职业发展计划的长期目标是为她提供开发、建立和管理独立的外部资助研究项目的技能，她是一家学术医学中心的终身教员。

DESCRIPTION (provided by applicant): This application for a K01 Mentored Career Development Award for Underrepresented Minorities is being submitted by Dr. Rukiyah Van Dross (Principal Investigator) and Dr. Jill C. Pelling (Sponsor). The application consists of two Phases for career development: Phase I (mentored, dependent) will consist of two-years of continuing postdoctoral supervision for Dr. Van Dross by Dr. Pelling, and Phase II (mentored, independent) consisting of 3 years of continued research by Dr. Van Dross in a more independent fashion as a research assistant professor in the Department of Pathology and Laboratory Medicine, but still working in space adjacent to Dr. Pelling's research laboratory with continued mentoring by Dr. Pelling. In Phase I Dr. Van Dross will work as a postdoctoral investigator in Dr. Pelling's laboratory, continuing to develop independent research skills in experimental design, data interpretation, manuscript/grant writing, graduate student/technician supervision, travel to scientific meetings and development of contacts with colleagues in the field of carcinogenesis and chemoprevention for purposes of establishing future research collaborations and developing a network of colleagues in the field who can advise Dr. Van Dross. The research project that Dr. Van Dross will work on during Phase I of her career development plan is presented in detail in this application, and is focused on specific aims to investigate the role of p38 MAP kinase in modulation of chemopreventive action by the bioflavonoid apigenin. This research project has been developed by Dr. Van Dross in consultation with Dr. Pelling, and its goals are clearly relevant to cancer biology and chemoprevention. The experimental approach proposed by Dr. Van Dross will extend her preliminary observations on apigenin induction of p38 MAP kinase and concomitant phosphorylation of p53 protein and apoptosis. The research proposed in this K01 application is separate from Dr. Pelling's NIH grant CA72987-05, entitled "Molecular mechanism of chemoprevention by apigenin," which focuses on induction of ERK by apigenin and downstream effects on p53 post-translational modification. In Phase II of the career development plan, Dr. Van Dross will be promoted to research assistant professor in the Department of Pathology and Laboratory Medicine (see Chairman's letter), assuming continued productivity toward research goals of the K01 grant. In Phase II Dr. Van Dross will continue to be mentored by Dr. Pelling in her research as well as in grant writing skills, manuscript writing, reviewing journal articles and professional contacts in her field. The research carried out by Dr. Van Dross during Phase II of her career development plan is outlined in detail in this application and will focus on investigating the protein/protein interactions of p38 MAP kinase and p53 and their role in apoptosis. The long-term goal of Dr. Van Dross' career development plan is to provide her with the skills to develop, establish and manage an independent externally-funded research program as a tenure-track faculty member at an academic medical center.