Aggressive Prostate Cancer: Linking Epigenomics and Genetics for Prevention

描述（由申请人提供）：K 05候选人是一名高级教员（教授），他积极参与癌症研究和指导已有二十多年。她是一位独立的研究者，在癌症预防方面开发并维持了一个充满活力的研究和培训计划。候选人拥有超过270篇科学出版物，并因其前列腺癌（PCa）研究而在国内和国际上得到认可（例如，流行病学、生物标志物、预防、结果）。候选人的研究计划有助于建立一个强大的环境和基础设施，将提供关键的支持，资源和机会，为年轻的研究人员在拟议的K 05奖。该奖项将为候选人提供所需的支持，使其能够投入更多的时间和精力实现职业发展目标，并成功推出下一代癌症预防年轻研究人员。 K 05提案有3个组成部分：1）职业计划; 2）研究计划; 3）指导计划。斯坦福大学博士的职业规划包括：1）推进基因组学，表观基因组学和分子生物学的知识; 2）增强她的研究技能，特别是与高通量数据分析相关的技能; 3）增强她的指导技能。职业生涯计划与拟议的研究和指导计划密切相关，并将包括学术课程，会议，领导一个新的期刊俱乐部，并在研究伦理课程教学。该研究计划旨在扩大PCa生物标志物的知识，并将测试表观基因组和遗传改变影响PCa进展到其侵袭性表型的假设。研究计划将：1）确定PCa肿瘤组织中全基因组DNA甲基化和基因表达谱是否与复发性和致死性PCa相关;并且，在本发明中，2）将来自甲基化和表达谱的排名靠前的基因与与PCA特异性死亡率相关的遗传变体联合收割机组合，以构建用于患者分层的生物标志物的整合组（惰性肿瘤与侵袭性肿瘤）可能从新的治疗和预防方法中获益最多。研究计划将利用基于人群的PCa患者队列（n= 1，458）以及可用数据和生物标本。指导计划是建立在候选人的经验，从与研究生，研究员和初级教师的工作，并将包括个人和小组的互动，旨在激励和建立K 05学员的研究和职业技能（例如，研究设计和方法，数据分析，撰写科学论文和赠款提案，在科学会议上发言）。学员将通过培训和其他赠款和奖项在候选人的研究学术环境中确定和支持。所有的数据，生物标本，和候选人的研究计划的资源将提供给培训这些年轻的科学家。

DESCRIPTION (provided by applicant): The K05 candidate is a senior faculty member (professor) who has been actively involved in cancer research and mentoring for over two decades. She is an independent investigator who has developed and sustained a vigorous research and training program in cancer prevention. The candidate has over 270 scientific publications and is recognized nationally and internationally for her prostate cancer (PCa) research (e.g., epidemiology, biomarkers, prevention, outcomes). The candidate's research program has been instrumental in building a robust environment and infrastructure that will provide critical support, resources, and opportunities for young investigators during the proposed K05 award. This award would provide needed support for the candidate to devote substantially more time and effort toward career development goals and successful launching of the next generation of young investigators in cancer prevention. The K05 proposal has 3 components: 1) Career Plan; 2) Research Plan; and, 3) Mentoring Plan. Dr. Stanford's Career Plan includes: 1) advancing knowledge of genomics, epigenomics, and molecular biology; 2) augmenting her research skills, particularly related to analyses of high-throughput data; and, 3) enhancing her mentoring skills. The career plan is strongly tied to the proposed research and mentoring plans, and will encompass academic courses, conferences, heading a new journal club, and teaching in the research ethics program. The Research Plan is aimed to expand knowledge of biomarkers for PCa, and will test the hypothesis that epigenomic and genetic alterations influence PCa progression to its aggressive phenotype. The research plan will: 1) determine whether genome-wide DNA methylation and gene expression profiles in PCa tumor tissue are associated with recurrent and lethal PCa; and, 2) combine top-ranked genes from the methylation and expression profiles with genetic variants associated with PCa-specific mortality to build an integrated panel of biomarkers for stratification of patients (indolent vs. aggressive tumors) who may benefit most from novel therapy and prevention approaches. The research plan will take advantage of a population-based cohort of PCa patients (n=1,458) with available data and biospecimens. The Mentoring Plan is built upon the candidate's experience gained from working with graduate students, fellows, and junior faculty, and will include both individual and group interactions aimed at inspiring and building the research and career skills of K05 mentees (e.g., study design and methodology, data analyses, writing scientific papers and grant proposals, presenting at scientific meetings). Trainees will be identified and supported through training and other grants and awards within the candidate's research-academic environment. All data, biospecimens, and resources from the candidate's research program will be made available for training these young scientists.