Mentoring Research in Precision Medicine for Lung Disease

肺部疾病精准医学的指导研究

• 批准号: 10301481
• 负责人: PRESCOTT G WOODRUFF
• 金额: $ 12.11万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-04-28 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10301481
• 关键词: African American population; Airway Disease; Applications Grants; Area; Asthma; Award; Biology; Characteristics; Chronic Obstructive Pulmonary Disease; Cilia; Clinical; Clinical Research; Consensus; Data; Development; Disease; Educational Curriculum; Educational process of instructing; Ensure; Equation; Faculty; Fortune; Funding; Genomics; Goals; Grant; Health; Human; Incubated; Individual; Inflammation; Institutional Review Boards; Interferons; Laboratories; Longitudinal cohort; Lung; Lung diseases; Maintenance; Measures; Medicine; Mentors; Methods; Modernization; Molecular; National Heart, Lung, and Blood Institute; Obstructive Lung Diseases; Pathologic; Pathway interactions; Patients; Physicians; Predictive Value; Publishing; Pulmonary function tests; Race; Research; Research Methodology; Resources; Respiratory Disease; Risk; Role; Sampling; Scientist; Series; Severities; Severity of illness; Smoker; Smoking; Societies; Structure; Symptoms; Systematic Bias; Testing; Time; Tissue Banks; Training; Translational Research; United States National Institutes of Health; Work; airway epithelium; base; career; clinical care; cohort; design; endoplasmic reticulum stress; experience; health disparity; human old age (65+); innovation; interest; laboratory experience; member; multidisciplinary; novel; patient oriented; patient oriented research; precision medicine; preservation; programs; pulmonary function; racial disparity; resilience; skills; success; targeted treatment; time use; tool; translational research program

PROJECT SUMMARY By combining a firm understanding of the design and conduct of rigorous human studies with the growing toolkit of the molecular biologist and geneticist, modern patient-oriented physician-scientists have the potential to overcome age-old barriers to the development of targeted therapies in common and morbid respiratory diseases. Accordingly, the first goal of this K24 Mentoring grant renewal application is to continue to protect my time for mentoring of young research scientists in patient oriented translational research in asthma and COPD. This work is a natural extension of work undertaken in the first funding period and builds on the success of my mentees and in further increases in NIH grant support of my research programs. These mentoring efforts have been strongly supported by UCSF through the provision of space to start and expand a “Pulmonary Precision Medicine Core Laboratory” that I direct and which provides scalable space and resources and a common area for didactics and informal research interactions for mentees in patient oriented research (POR). This K24 grant has significantly protected my time and provided resources (some matched by Divisional resources) to ensure the success of this endeavor. In a new direction that I have recently been inspired to pursue, the second goal of this K24 renewal is to support my mentoring efforts in the study of racial disparities in how we assess and treat obstructive lung disease. This new research area flows directly from new data that I and two mentees generated in SPIROMICS, the longitudinal cohort that I direct. These data highlight systematic bias that results from race-adjusted pulmonary function testing equations that are used in research and clinical care. In its structure, this K24 renewal application proposes three scientific aims and a fourth organizational aim which describes my approach to expanding the core training laboratory and seminar series that I have developed by leveraging larger new space that is being conferred to me by the Pulmonary Division and Department of Medicine at UCSF based on the success of these programs to date. Aim 1 will test the hypothesis that airway epithelial endoplasmic reticulum stress identifies a common pathway related to both T2 and interferon-driven inflammation and which is associated with increased disease severity and exacerbation risk in asthma and COPD. Aim 2 will test the hypothesis that maintenance of cilia and detoxifying pathways in the airway epithelium of smokers is associated with clinical resilience in smokers. Aim 3 will test the hypothesis that our current practices for lung function normalization are fundamentally biased and that race-agnostic PFT equations better measure health and disease in our diverse society. Aim 4 will test the hypothesis that the “Pulmonary Precision Medicine Core Laboratory” that I have developed will enhance multidisciplinary training across a range of trainees with diverse scientific backgrounds and enable them to expand their capabilities well beyond their existing core training, while focusing on human studies and POR.

项目总结 通过将对设计和进行严格的人体研究的坚定理解与日益增长的 分子生物学家和遗传学家的工具包，现代以患者为导向的内科科学家有潜力 克服常见和病态呼吸道靶向治疗发展的古老障碍 疾病。因此，此次K24辅导助学金续签申请的第一个目标是继续保护我的 是时候在哮喘和慢性阻塞性肺病的面向患者的转化性研究中指导年轻的研究科学家了。 这项工作是在第一个供资期间开展的工作的自然延伸，并建立在我的 并进一步增加了NIH对我研究项目的拨款支持。这些指导努力已经 得到了加州大学旧金山分校的大力支持，通过提供空间来启动和扩大一项“肺精密手术” 提供可扩展的空间和资源以及一个公共区域 在以患者为中心的研究(POR)中，为指导对象提供教学和非正式研究互动。这笔K24拨款 极大地保护了我的时间，并提供了资源(其中一些与部门资源相匹配)以确保 这一努力的成功。在我最近受到启发追求的一个新方向上，第二个目标 K24的更新是为了支持我在研究种族差异方面的指导努力，这些差异是我们如何评估和 治疗阻塞性肺病。这个新的研究领域直接来自于我和两个被指导者的新数据 在SPIROMICS中产生的，我指导的纵向队列。这些数据突显了系统性偏差的结果 来自用于研究和临床护理的经种族调整的肺功能测试方程式。在ITS中 结构，这次K24续签申请提出了三个科学目标和第四个组织目标， 描述我扩展核心培训实验室和研讨会系列的方法，这些实验室和研讨会系列是由 利用肺科和新闻部授予我的更大的新空间 加州大学旧金山分校的医学研究是基于这些项目迄今的成功。目标1将检验这样的假设：呼吸道 上皮内质网应激识别与T2和干扰素驱动的共同途径 炎症，与哮喘和哮喘的疾病严重性和恶化风险增加有关 慢性阻塞性肺疾病（慢阻肺）。目标2将验证这样一种假设，即纤毛和排毒途径在呼吸道中的维持 吸烟者的上皮细胞与吸烟者的临床弹性有关。目标3将测试这样的假设：我们的 目前肺功能正常化的做法从根本上是有偏见的，而且不受种族因素影响的PFT 等式更好地衡量了我们多样化社会中的健康和疾病。目标4将检验这一假设 我所开发的“肺精准医学核心实验室”将加强多学科培训 涵盖具有不同科学背景的一系列受训人员，使他们能够很好地扩展自己的能力 除了他们现有的核心培训外，还将重点放在人类研究和POR上。