Aggressive Prostate Cancer: Linking Epigenomics and Genetics for Prevention

侵袭性前列腺癌：将表观基因组学和遗传学联系起来进行预防

基本信息

批准号：
8635188
负责人：
JANET L STANFORD
金额：
$ 8.9万
依托单位：
FRED HUTCHINSON CANCER RESEARCH CENTER
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-01-09 至 2018-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8635188
关键词：
Adverse effects Age Applications Grants Aspirin Award Biological Markers Biopsy Biopsy Specimen Cancer Control Cancer Patient Cessation of life Clinical Collaborations Complex Cox Proportional Hazards Models DNA DNA Methylation Data Data Analyses Data Collection Development Diagnosis Diagnostic Dietary intake Disease Educational process of instructing Environment Environmental Exposure Epidemiology Epigenetic Process Etiology Event Faculty Gene Expression Genes Genetic Genetic Markers Genetic Transcription Genomics Gleason Grade for Prostate Cancer Goals Government Grant Guidelines Head Heart Human Immune response Individual Indolent Inherited Journals Knowledge Lead Link Malignant Neoplasms Malignant neoplasm of prostate Measures Mediating Mentors Messenger RNA Methodology Methylation Modality Molecular Molecular Biology Molecular Profiling Morbidity - disease rate Mutation Neoplasm Metastasis Obesity Outcome Paper Pathogenesis Pathologic Pathway interactions Patients Phenotype Play Predisposition Prevention Prevention approach Prevention therapy Prognostic Marker Promoter Regions Publications Race Radical Prostatectomy Recurrence Research Research Design Research Ethics Research Infrastructure Research Personnel Research Project Grants Research Training Resources Role Sampling Scientist Senior Scientist Award Single Nucleotide Polymorphism Smoking Staging Stratification Structure of base of prostate Subgroup TMPRSS2 gene Testing Time Training Training Programs Translational Research Working Group Tumor Suppressor Genes Tumor Tissue Variant Work Writing anticancer research base cancer diagnosis cancer genomics cancer prevention cancer recurrence cancer risk cancer therapy career career development clinically significant cohort epigenomics experience fight against genetic variant genome-wide graduate student hazard high risk improved industry partner investigator training meetings member men mortality next generation novel outcome forecast population based professor prognostic programs public health relevance research and development risk variant skills skills training symposium tumor tumor growth tumor progression

项目摘要

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.

描述（由申请人提供）：K05候选人是一名高级教职员工（教授），他已经积极参与癌症研究和指导已有二十年了。她是一名独立的研究者，曾在癌症预防方面发展并维持了一项有力的研究和培训计划。该候选人拥有270多个科学出版物，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）而在国内和国际上得到认可。该候选人的研究计划在建立强大的环境和基础设施方面发挥了作用，该环境和基础设施将为拟议的K05颁奖典礼提供重要的支持，资源和机会。该奖项将为候选人提供所需的支持，以便将更多的时间和精力用于职业发展目标，并成功地推出了下一代年轻调查员在癌症预防方面。 K05提案有3个组成部分：1）职业计划； 2）研究计划； 3）指导计划。斯坦福大学的职业计划包括：1）促进基因组学，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的分析有关； 3）增强她的指导能力。职业计划与拟议的研究和指导计划密切相关，并将涵盖学术课程，会议，领导新的期刊俱乐部以及研究伦理学计划的教学。该研究计划的目的是扩大对PCA生物标志物的知识，并将检验以下假设：表观基因组和遗传改变会影响PCA的进展到其侵略性表型。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命PCA有关； 2）将甲基化和表达谱的顶级基因与与PCA特异性死亡率相关的遗传变异结合在一起，以构建一个综合的生物标志物，以分层患者（侵略性与攻击性肿瘤）分层，这些综合体可能受益于新型治疗和预防方法。该研究计划将利用基于人群的PCA患者队列（n = 1,458），并具有可用的数据和生物测量。指导计划建立在候选人与研究生，研究员和初级教师中获得的经验，并将包括旨在启发和建立K05受训者的研究和职业技能的个人和团体互动（例如，研究设计和方法论，数据分析，数据分析，撰写科学论文和赠款提议，在科学介绍中介绍了科学会议）。通过培训以及候选人研究学术环境中的其他赠款和奖励，将确定和支持学员。候选人研究计划中的所有数据，生物测量和资源都将用于培训这些年轻科学家。