Midcareer Award in Translational Immunology of Aging

描述(申请人提供)：本申请K24职业中期调查员奖的患者为导向的研究，旨在促进指导活动和职业发展的重点是衰老的免疫学。值得注意的是，目前NIA没有其他资助的K24致力于翻译免疫学。他是耶鲁医学院的医学副教授，受过内科和传染病方面的培训，此外还拥有遗传学博士学位，是一名训练有素的免疫学家。肖博士是公认的研究人类免疫系统衰老的权威；他的实验室对先天免疫系统的衰老特别感兴趣，并就衰老对人类Toll样受体(TLR)功能的影响进行了迄今为止规模最大、最全面的研究。这些研究明确了先天免疫系统中免疫衰老的特征，并证明了TLR功能与获得性免疫反应之间的联系，如对流感疫苗的抗体反应。尽管邵逸夫已经指导了几名仍在学术研究岗位上的年轻研究人员，但目前，他的指导活动必须与行政、临床和研究承诺相竞争。在这方面，他正处于职业生涯的理想点，通过K24机制扩大自己的辅导活动。肖博士最近启动了两个新资助的以患者为中心的研究项目--第一个是他担任NIAID合同的项目负责人，该合同专注于了解与生俱来的免疫模式识别受体功能与年龄相关的变化。在第二个案例中，他是美国国立卫生研究院人类免疫表型鉴定联盟U19中心拨款中的R01的PI。该项目将阐明流感疫苗反应的免疫学和基因表达特征，并将确定衰老和虚弱如何影响这些特征。这两项倡议构成了制定指导和职业发展计划的平台，旨在培养研究衰老免疫学的新研究人员。此外，这一应用还将直接支持另外两个项目：第一个是关于感染艾滋病毒的年轻人和老年人的先天免疫功能的试验性研究。第二个探索性项目利用NIA赞助的耶鲁大学正在进行的临床试验，对直立喂养姿势和加强口腔护理的疗养院肺炎预防进行多组分干预。我们将评估先天免疫功能与一项正在进行的关于加强口腔护理的口腔微生物组组成变化的子研究结果之间的关系。这一研究平台将得到职业发展活动的支持，其中包括临床老年病学、计算生物学和老年生物统计学方面的教程。总而言之，这一计划将进一步加强PI作为下一代研究人员的导师的角色，他们将促进我们对老龄化背景下的人类免疫学的理解。

DESCRIPTION (provided by applicant): This application for a K24 Midcareer Investigator Award in Patient-Oriented Research is intended to promote mentoring activities and career development focused on the immunology of aging. Notably, no other currently funded K24 at the NIA is devoted to translational immunology. The PI, Dr. Shaw, is Associate Professor of Medicine at the Yale School of Medicine; he is trained in Internal Medicine and Infectious Disease, and in addition has a Ph.D. in Genetics and is a trained immunologist. Dr. Shaw is recognized as an authority on the aging of the human immune system; his lab has a special interest in aging of the innate immune system, and has carried out the largest and most comprehensive studies to date of the consequences of aging on human Toll-like Receptor (TLR) function. These studies defined features of immunosenescence in the innate immune system, and also demonstrated the linkage between TLR function and adaptive immune responses such as antibody response to influenza vaccine. Although Dr. Shaw has mentored several young investigators who remain in academic research positions, at present his mentoring activities must compete with administrative, clinical and research commitments. In this regard, he is at an ideal point in his career to expand his mentoring activities through the K24 mechanism. Dr. Shaw has recently begun two newly funded projects in patient- oriented research-in the first, he serves as Project Leader for an NIAID contract focusing on understanding age-associated alterations in innate immune pattern recognition receptor function. In the second, he is the PI of an R01 within a U19 Center Grant that is part of the NIH Human Immunophenotyping Consortium. This project will elucidate immunologic and gene expression signatures of influenza vaccine response, and will determine how aging and frailty affect these signatures. These two initiatives form the platform for development of a mentoring and career development plan directed to developing new investigators studying the immunology of aging. In addition, two additional projects would be directly supported by this application: the first, a pilot study of innate immune function in young and older individuals with HIV infection. The second exploratory project leverages an ongoing NIA-sponsored clinical trial at Yale of a multicomponent intervention of upright feeding position and enhanced oral care on nursing home pneumonia prevention. We will evaluate the relationship between innate immune function and results of an ongoing substudy on alterations in oral microbiome composition with enhanced oral care. This research platform will be supported by career development activities that include tutorials in clinical geriatrics, computational biology, and gerontologic biostatistic. Taken together, this program will further enhance the PI's role as a mentor to the next generation of investigators who will advance our understanding of human immunology in the context of aging.