Aggressive Prostate Cancer: Linking Epigenomics and Genetics for Prevention

描述（由申请人提供）：K05 候选人是一位高级教员（教授），二十多年来一直积极参与癌症研究和指导。她是一名独立调查员，制定并维持了强有力的癌症预防研究和培训计划。该候选人发表了 270 多篇科学出版物，并因其前列腺癌 (PCa) 研究（例如流行病学、生物标志物、预防、结果）而获得国内外认可。候选人的研究项目有助于建立一个强大的环境和基础设施，为年轻研究人员在拟议的 K05 奖项期间提供关键的支持、资源和机会。该奖项将为候选人提供必要的支持，使其能够投入更多的时间和精力实现职业发展目标，并成功培养下一代癌症预防领域的年轻研究人员。 K05提案有3个组成部分：1）职业规划； 2）研究计划；以及，3) 指导计划。斯坦福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) 提高她的指导技能。职业规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、领导新的期刊俱乐部以及研究伦理项目的教学。该研究计划旨在扩展对 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 进展为其侵袭性表型的假设。该研究计划将：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； 2) 将甲基化和表达谱中排名靠前的基因与与 PCa 特异性死亡率相关的遗传变异相结合，构建一个综合的生物标志物组，用于对可能从新的治疗和预防方法中受益最多的患者（惰性肿瘤与侵袭性肿瘤）进行分层。该研究计划将利用基于人群的 PCa 患者队列（n=1,458）以及可用的数据和生物样本。指导计划建立在候选人与研究生、研究员和初级教师合作的经验基础上，并将包括个人和小组互动，旨在激发和培养 K05 受训者的研究和职业技能（例如，研究设计和方法、数据分析、撰写科学论文和资助提案、在科学会议上发言）。将通过候选人研究学术环境中的培训和其他资助和奖励来确定和支持受训者。候选人研究项目的所有数据、生物样本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.