Aggressive Prostate Cancer: Linking Epigenomics and Genetics for Prevention

描述(由申请人提供)：K05候选人是一名资深教员(教授)，积极参与癌症研究和指导超过20年。她是一名独立调查员，在癌症预防方面制定并维持了一项强有力的研究和培训计划。这位候选人拥有270多篇科学出版物，她的前列腺癌(PCA)研究(例如，流行病学、生物标记物、预防、结果)在国内和国际上都得到了认可。候选人的研究计划在建立健全的环境和基础设施方面发挥了重要作用，这些环境和基础设施将在拟议的K05奖项期间为年轻研究人员提供关键支持、资源和机会。这一奖项将为候选人提供必要的支持，以便为实现职业发展目标和成功启动下一代年轻癌症预防研究人员投入更多的时间和精力。K05计划包括3个部分：1)职业规划；2)研究计划；3)指导计划。斯坦福博士的职业规划包括：1)提高基因组学、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；以及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，将包括学术课程、会议、领导一个新的期刊俱乐部，以及在研究伦理计划中授课。该研究计划旨在扩大对PCa生物标志物的了解，并将检验表观基因组和遗传改变影响PCa向侵袭性表型发展的假设。该研究计划将：1)确定全基因组DNA甲基化和PCa肿瘤组织中的基因表达谱是否与复发和致死性PCa有关；以及2)将甲基化和表达谱中的顶级基因与与PCa特异性死亡率相关的遗传变异结合起来，建立一个综合的生物标记物小组，用于对可能从新的治疗和预防方法中受益最大的患者(惰性肿瘤和侵袭性肿瘤)进行分层。该研究计划将利用以人群为基础的前列腺癌患者队列(n=1,458)，并利用现有的数据和生物样本。导师计划建立在候选人从与研究生、研究员和初级教师合作中获得的经验基础上，并将包括旨在激励和培养K05名导师的研究和职业技能的个人和小组互动(例如，研究设计和方法、数据分析、撰写科学论文和拨款提案、在科学会议上发表)。受训者将在候选人的研究-学术环境中通过培训和其他拨款和奖励来确定和支持。候选人研究计划中的所有数据、生物样品和资源都将用于培训这些年轻科学家。

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.