Pilot and Exploratory Core

摘要/摘要 波士顿胡椒OAIC的目标是支持一个跨学科的研究计划，以促进 功能促进疗法(FPTs)的发展。在审查办的总体任务范围内，飞行员 和探索性研究核心(PESC)将通过资助试点和 探索性研究，并提供指导和基础设施核心支持。《公约》的总体目标 PESC将使研究人员发起的早期研究能够获得开发 雄厚、资金充足和富有成效的烟草控制框架下的翻译研究项目。PESC的首要目标 在这次更新的背景下，是建立在我们伊斯兰会议组织主题的科学基础上，而次要的 目标是帮助那些研究与我们的主题相一致的科学家建立职业生涯。目标1将 继续为早期创新和跨学科研究提供翻译渠道，通过提供 利用我们的Boston Pepper OAIC核心和基础设施生成概念验证的资金 临床前数据，以加快FPTS的开发，靶标识别的机制研究或 建立FPT对骨骼肌和身体功能产生影响的假设；以及初步测试 人类研究参与者或动物模型中的转译干预或研究方案以确保安全， 可行性，或最佳时间进程或剂量的确定。AIM 2将促进PESC之间的连接 调查员和伊斯兰会议组织资源核心。目标3将催化试点和探索性项目成为高质量的同行- 审查出版物、授权申请和知识产权/专利。 我们的波士顿胡椒OAIC指导委员会选出了三个创新的候选项目 在我们的续签中考虑PESC的支持，从#年收到的19份申请中 响应广为宣传的应用程序请求(RFA)。这三个坦率的项目都很好 与OAIC通过阐明机制促进FPTS发展的使命保持一致，目标 鉴定、模式生物的概念验证研究、流行病学调查和随机试验， 并将从我们的资源核心的使用中受益。这三个项目建立在创新的基础上 细胞衰老在间质性肺疾病中作用的假说和次优转归 来自老年捐赠者的移植器官，以及早期生活应激影响的表观遗传学机制 变性人的老龄化轨迹。PES-1评估移植较老的器官是否启动 衰老细胞通过衰老相关分泌表型(SASP)的传播 对老年人身体功能产生不利影响的炎症性项目。PES-2将检查 衰老相关生物标志物在提高老年痴呆早期识别和预测中的作用 肺纤维化(PF)是基于肺部影像的间质性肺异常(ILA)。PES-3 将评估压力驱动的变性人表观遗传年龄和炎症的加速。

SUMMARY / ABSTRACT The aim of the Boston Pepper OAIC is to support an interdisciplinary research program that fosters the development of function promoting therapies (FPTs). Within the context of the OAIC's overall mission, the Pilot and Exploratory Studies Core (PESC) will catalyze scientific advances in FPTs through funding of pilot and exploratory studies, and provision of mentorship and infrastructural core support. The overall objective of the PESC is to enable early stage investigator-initiated studies to acquire the pilot data needed to develop a robust, well-funded, and productive translational research projects of FPTs. The primary objective of the PESC in the context of this renewal is to build upon the science underlying our OAIC theme, while a secondary objective is to help build the careers of scientists whose research is aligned with our theme. Aim 1 will continue with our translational pipeline for early stage innovative and interdisciplinary research by providing funding that leverages our Boston Pepper OAIC cores and infrastructure for the generation of proof-of-concept preclinical data to expedite the development of FPTs, mechanistic studies for target identification or hypotheses building by which FPTs exert effects on skeletal muscle and physical function; and pilot testing of translational interventions or research protocols in human study participants or animal models for safety, feasibility, or determination of optimal time course or dosage. Aim 2 will foster connectivity between PESC investigators and OAIC resource cores. Aim 3 will catalyze pilot and exploratory projects into high quality peer- reviewed publications, grant applications, and intellectual property/patents. Our Boston Pepper OAIC Steering Commmitteee selected three innovative candidate projects for consideration of PESC support in our renewal, from among a pool of 19 applications that were received in response to a widely advertised request for applications (RFA). These three canddidate projects are well aligned with the OAIC's mission of promoting the development of FPTs by mechanism elucidation, target identification, proof-of-concept studies in model organisms, epidemiolgical investigation, and randomized trials, and would benefit from the use of our resource cores. The three projects are founded on innovative hypotheses of the role of cellular senescence in interstitial lung disease and suboptimal outcomes of transplanted organs from older donors, as well as epigenetic mechanisms by which early life stress affects the trajectory of aging among transgender people. PES-1 evaluates whether transplanting older organs initiates the spread of senescent cells through senescence-associated secretory phenotype (SASP) linked inflammatory programs that adversely influence physical function in older adults. PES-2 will examine the role of senescence-associated biomarkers in improving the identification and prediction of early stage of pulmonary fibrosis (PF) identified as interstitial lung abnormalities (ILA) based on pulmonary imaging. PES-3 will evaluate stress-driven acceleration of epigenetic age and inflammation in transgender adults.