Risk for Lung Cancer Asthma and COPD; Integrating Clinical and Airway Biomarker

描述(由申请者提供)：这项K24奖项提案的总体目标是进一步将Spivack博士发展成为一名以患者为中心的特殊跨学科研究导师，能够指导学员从提出临床假说到制定一系列可回答的组成部分问题。指导作用的关键组成部分将包括阐明相关人类研究设计的关键方面；在适用的情况下，通过与适当的实验室支持合作，创造性地采购和分析相关组织生物标记物；以及参与复杂的数据分析技术，以临床有意义的方式最终解决假说。因此，该提案的总体目标是支持这一翻译指导职能。具体目标是： 1)为PI提供受保护的时间，以进一步培训流行病学和统计学，特别是在多维观察数据集的累积和分析方面，包括病例对照/横断面和具有时间维度的预期队列。这将包括那些援引遗传数据分析的研究，以及在预防试验设计和分析中。 2)在项目期间的任何时间，为一至两名初级临床教员提供临床-翻译指导，并连续轮换两至四名肺内科或内科肿瘤学博士后临床研究员。 3)启动基于队列的前瞻性临床风险评估，调用常见肺部疾病(肺癌、哮喘、COPD)的临床和呼吸道特异性分子生物标记物分析，以促进早期发现和预防策略的制定。 Spivack实验室目前开发、采样、积累和分析人群的能力，以及构思、开发和应用最先进的分子方法对同一人群进行呼吸道疾病生物标记物分析的能力，为临床和其他博士后实习生提供了非常独特的培训机会，涉及医学、肺部医学、肿瘤学和一般的翻译研究。在K24奖项的推动下，指导经验将得到显著增强，并将以跨学科的方式转向评估现有的潜在队列。研究问题从根本上是临床的：(1)我们能否识别肺癌、哮喘和COPD的风险个体，以促进早期发现策略？(2)我们能否使用预防策略对个体进行干预，以降低风险？

DESCRIPTION (provided by applicant): The overall goal of this K24 award proposal is to further the development of Dr. Spivack into an exceptional trans-disciplinary patient-oriented research mentor, capable of guiding trainees from developing a clinical hypothesis to formulation of a series of answerable component questions. Key components of that mentorship role will include the articulation of critical aspects of relevant human study design; invoking, where applicable, the creative procurement and analyses of relevant tissue biomarkers by collaboration with appropriate laboratory support; and engagement of sophisticated data analytic techniques to definitively address the hypotheses in a clinically-meaningful manner. The overall aim of the proposal is therefore to support this translational mentorship function. The Specific Aims are: 1) Provide protected time for the PI to further train in epidemiology and statistics, particularly with respect to accrual and analysis of multi-dimensional observational datasets, both case-control/cross-sectional, and prospective cohorts with a time dimension. This will include those studies invoking genetic data analyses, and in prevention trials design and analyses. 2) Provide clinical-translational mentorship for one to two junior clinical faculty members, and a continuous rotation of two to four Pulmonary Medicine or Medical Oncology post-doctoral clinical fellows, at any given time over the project period. 3) Initiate the assessment of prospective cohort-based clinical risk, invoking clinical and airway-specific molecular biomarker analyses of common lung diseases (lung cancer, asthma, COPD), for facilitating the development of early detection and prevention strategies. The current capacity of the Spivack laboratory to develop, sample, accrue and analyze a population, and to conceive, develop and apply state-of-art molecular methodologies for airway disease biomarker analyses to the same population, provides a very unique training opportunity for clinical and other post-doctoral trainees in Medicine, Pulmonary Medicine, Oncology, and in translational research in general. Facilitated by a K24 award, the mentoring experience will be markedly enhanced, as will a shift to evaluating existing prospective cohorts, in a trans-disciplinary manner. The research questions are fundamentally clinical: (1) Can we identify individuals at risk for lung cancer, asthma, and COPD, to facilitate early detection strategies? (2) Can we intervene in individuals, to reduce that risk, using preventive strategies?