Aggressive Prostate Cancer: Linking Epigenomics and Genetics for Prevention

描述（申请人提供）：K05候选人是一名资深教师（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，在癌症预防方面开展并维持了一项强有力的研究和培训计划。该候选人发表了270多篇科学论文，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）在国内和国际上得到认可。候选人的研究项目在建立一个强大的环境和基础设施方面发挥了重要作用，将在拟议的K05奖期间为年轻的研究人员提供关键的支持、资源和机会。该奖项将为候选人提供所需的支持，使其投入更多的时间和精力实现职业发展目标，并成功启动下一代癌症预防领域的年轻研究人员。K05提案包括三个部分：1)职业规划；2)研究计划；3)师徒计划。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)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，将包括学术课程、会议、领导一个新的期刊俱乐部，以及研究伦理项目的教学。该研究计划旨在扩大前列腺癌生物标志物的知识，并将测试表观基因组和遗传改变影响前列腺癌进展到其侵袭性表型的假设。研究计划将：1)确定前列腺癌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前列腺癌相关；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结合起来，建立一个综合的生物标志物面板，用于患者分层（惰性肿瘤与侵袭性肿瘤），这些患者可能从新的治疗和预防方法中获益最多。该研究计划将利用基于人群的PCa患者队列（n= 1458）的可用数据和生物标本。指导计划是建立在候选人与研究生，研究员和初级教师一起工作的经验基础上的，并将包括个人和小组互动，旨在激励和建立K05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赠款和奖励来确定和支持。候选人研究项目的所有数据、生物标本和资源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.