ESTABLISHED INVESTIGATOR AWARD IN CANCER PREVENTION AND CONTROL

描述(申请人提供)：K05奖将为Thomas L Vaughan博士提供保护时间(30%FTE)，以继续研究与食管腺癌(EA)的病因和预防相关的关键研究问题。在过去的40年里，食管腺癌在美国和许多西方国家的发病率显著上升(总体发病率增加了6倍，白人男性增加了10倍)。它还将提供受保护的时间(20%FTE)，以继续他在华盛顿大学(UW)、弗雷德·哈钦森癌症研究中心(FHCRC)和外部机构的学生、博士后研究员和初级研究员的广泛指导活动。 他目前获奖的前四年(2007年7月至2011年10月)为他提供了关键的保护时间，使他能够专注于进一步发展和加强他的EA研究计划。当前奖项的目标1用于资助他对以前收集的数据和来自当地研究的生物标本进行分析的努力，这些研究的资金已经到期。到目前为止，这种集中的努力已经发表了20篇论文，提交了8篇手稿，其中许多涉及到他对博士后和博士后导师的直接监督。沃恩博士是2005年国际巴雷特和食管腺癌联盟(Beacon)的联合创始人之一，该联盟得到了NCI的部分支持。他当选为第一届指导委员会主席，并继续担任这一职务。当前奖项的目标2涉及将Beacon建立为研究EA病因学和预防的重要纽带。在当前奖项的头四年里，该联盟的成员人数大约翻了一番，年度研讨会通常有40-50人参加。增加了临床胃肠病学、分子生物学、生理学、遗传学、进化生物学和群体遗传学方面的其他专业知识，以显著扩大可用于计划和开展新研究的专家技能和知识的范围。六个研究项目得到了NCI、NIDDK、英国癌症研究中心和瑞典癌症协会的资助。在过去的两年里，又出版或提交了六份手稿，还有几份手稿已进入最后阶段。目前奖项的目标3涉及在Beacon内开发新的合作研究项目。这项奖励让沃恩博士获得了多重PI拨款(2009年底获得资金)，用于一项涉及14个地点和约8500名参与者的全基因组关联研究。K05奖项不仅为开发这一后勤复杂的拨款申请提供了受保护的时间，而且为Vaughan博士提供了重要的遗传流行病学培训机会(例如，欢迎信托常见疾病遗传学会议；受邀参加Illumina美洲科学峰会，并作为昆士兰医学研究所的访问学者)。 在更新期间提出的研究活动代表了在当前K05奖励期间开发的想法和项目的直接演变。第一个目标是利用Beacon丰富的数据资源开发针对特定人群绝对风险的风险和预测模型，这将有助于a)卫生政策的制定，b)教育，c) 临床决策，以及d)设计未来研究。它的目的是解决EA控制的关键障碍，通过确保EA预防干预措施最佳地利用关于预测肿瘤进展、治疗反应和生存的风险因素、保护因素和生物标记物的知识，促进EA预防干预措施的成本和有效性的改善。第二个目标包括他在Beacon继续发挥科学领导作用。具体地说，这涉及与联合会成员一起开发和积极参与正在进行的和新的汇集分析，包括正在进行的信标研究，如分析端粒长度、IGF相关标记和脂肪因子；以及正在进行的BE和EA全基因组关联研究的辅助分析。它还涉及与信标调查人员和被辅导者开发新的合作研究项目，这些项目将利用代表的不同人群以及现有的具有良好特征的组织银行。 沃恩博士在指导研究生和博士后研究员以及流行病学和相关学科的初级教员方面有着良好的记录。他是NCI资助的癌症流行病学和生物统计学培训基金的主任，该基金资助9名博士后和4名博士后学员，并管理着期刊俱乐部。他曾担任过29个硕士论文委员会和26个博士论文委员会的客座教授。K05资助的辅导活动将包括：i)与他在培训补助金上的职责相关的活动；ii)他对其他流行病学系和相关系受训人员的持续辅导；以及iii)在威斯康星大学、FHCRC和外部机构的初级教员的辅导。每年，他计划与两到三名博士后学生、一到两名博士后研究员和一到两名初级教员密切合作。 公共卫生相关性：该奖项将为托马斯·L·沃恩博士提供受保护的时间和资源，让他从事与食管腺癌病因和预防相关的关键研究问题，并解决更有效的预防和控制计划的关键障碍。它还将提供受保护的时间来继续他广泛的指导 多个机构的学生、博士后研究员和初级研究员的流行病学

DESCRIPTION (provided by applicant): The K05 award will provide Dr. Thomas L Vaughan with protected time (30% FTE) to continue to pursue key research questions related to the etiology and prevention of esophageal adenocarcinoma (EA), a cancer that has undergone a remarkable increase in incidence (6-fold overall, and 10-fold among white males) in the US and many western countries during the past four decades. It will also provide for protected time (20% FTE) to continue his extensive mentoring activities of students, postdoctoral fellows and junior investigators at the University of Washington (UW), the Fred Hutchinson Cancer Research Center (FHCRC) and outside institutions. The first four years of his current award (July 2007 - October 2011) provided critical protected time for him to focus on further developing and strengthening his research program on EA. Aim 1 of the current award funds his effort on analyses of previously-collected data and biospecimens from local studies with expired funding. This concentrated effort has thus far resulted in 20 published papers, and eight submitted manuscripts, many involving his direct supervision of pre- and postdoctoral mentees. Dr. Vaughan was one of the co-founders of the international Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) in 2005, supported in part by NCI. He was elected as first Steering Committee Chair and continues in that role. Aim 2 of the current award involves establishing BEACON as an important nexus for research on etiology and prevention of EA. During the first four years of the current award, membership in the consortium has approximately doubled, with annual workshops typically involving 40-50 attendees. Additional expertise in clinical gastroenterology, molecular biology, physiology, genetics, evolutionary biology and population genetics has been added to significantly expand the range of expert skill and knowledge available to plan and carry out new studies. Six research projects have been by grants from the NCI, NIDDK, Cancer Research UK, and the Swedish Cancer Society. Over the past two years, a further six manuscripts have been published or submitted and several more are in the final phases of development. Aim 3 of the current award involves development of new collaborative research projects within BEACON. The award allowed Dr. Vaughan to develop a multiple PI grant (funded in late 2009) for a genome-wide association study involving 14 sites and about 8,500 participants. The K05 award was key in providing not only protected time to develop this logistically-complicated grant application, but important training opportunities for Dr. Vaughan in genetic epidemiology (e.g., Welcome Trust conference on genetics of common diseases; invited participation at the Illumina Americas Scientific Summit and as a visiting scholar at Queensland Institute of Medical Research.) Proposed research activities during the renewal period represent a direct evolution of ideas and projects developed during the current K05 award period. The first aim will utilize the rich data resources of BEACON to develop risk and prediction models which are tailored to the absolute risk of specific populations that will be useful for a) health policy development, b) education, c) clinical decision-making, and d) designing future research. This aims address critical barriers to EA control by facilitating improvement in the costs and effectiveness of EA prevention interventions by ensuring that they make optimum use of knowledge regarding risk factors, protective factors and biomarkers that predict neoplastic progression, response to therapy and survival. The second aim encompasses his continued scientific leadership role in BEACON. Specifically this involves developing and actively participating in ongoing and new pooled analyses with the Consortium members, including ongoing BEACON studies such as analysis of telomere length, IGF-related markers, and adipokines; as well as ancillary analyses to the ongoing genome-wide association study of BE and EA. It also involves developing new collaborative research projects with BEACON investigators and mentees that will take advantage of the diverse populations represented, along with existing banks of well-characterized tissues. Dr. Vaughan has a well-established track record of mentoring graduate students and postdoctoral fellows, as well as junior faculty in Epidemiology and related disciplines. He is Director of an NCI-funded Cancer Epidemiology and Biostatistics Training Grant which funds nine predoctoral and four postdoctoral trainees and runs the journal club. He guest lectures in established epidemiology courses, and has served on 29 master's thesis committees, and 26 doctoral dissertation committees. Mentoring activities funded by the K05 will include: i) those associated with his responsibilities on the training grant, ii) his ongoing mentoring of other trainees from Epidemiology and related departments, and iii) mentoring junior faculty at the UW, FHCRC and outside institutions. Each year, he plans to work closely with two to three predoctoral students, one to two postdoctoral fellows; and one to two junior faculty members. PUBLIC HEALTH RELEVANCE: This award will provide Dr. Thomas L Vaughan with protected time and resources to pursue key research questions related to the etiology and prevention of esophageal adenocarcinoma, and address critical barriers to a more effective program of prevention and control. It will also provide for protected time to continue his extensive mentoring in epidemiology of students, postdoctoral fellows and junior investigators at multiple institutions