Pilot and Exploratory Core

总结/摘要 波士顿胡椒OAIC的目的是支持一个跨学科的研究计划，促进 功能促进疗法（FPT）。在审计和调查办公室的总体使命范围内， 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的核心支持。的总体目标 PESC是为了使早期阶段的制冷剂启动的研究，以获得试点数据所需的发展， 强大的，资金充足的，富有成效的FPT转化研究项目。PESC的主要目标 在这种更新的背景下，是建立在我们OAIC主题的科学基础上，而第二个 我们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 继续我们的翻译管道为早期阶段的创新和跨学科的研究，提供 利用我们的Boston Pepper OAIC核心和基础设施进行概念验证的资金 临床前数据，以加快FPT的开发，靶点鉴定的机制研究，或 FPT对骨骼肌和身体功能产生影响的假设建立;以及 在人类研究参与者或动物模型中的安全性转化干预或研究方案， 可行性，或确定最佳的时间进程或剂量。目标2将促进PESC之间的联系 调查员和审调处资源核心。目标3将促进试点和探索性项目成为高质量的同行项目， 审查出版物、资助申请和知识产权/专利。 我们的波士顿胡椒OAIC指导委员会选择了三个创新的候选项目， 考虑PESC的支持，在我们的更新，从19个申请，收到了在 对广泛宣传的应用程序请求（RFA）的响应。这三个canddidate项目很好 与OAIC通过机制阐明促进FPT发展的使命相一致， 鉴定、模式生物概念验证研究、流行病学调查和随机试验， 并将受益于我们的资源核心的使用。这三个项目是建立在创新 细胞衰老在间质性肺疾病中的作用的假说和 老年捐赠者的器官移植，以及早期生活压力影响器官移植的表观遗传机制。 跨性别人群的衰老轨迹。PES-1评估移植较旧的器官是否会引发 衰老细胞通过衰老相关分泌表型（SASP）扩散， 炎症程序对老年人的身体功能产生不利影响。PES-2将检查 衰老相关生物标志物在改善衰老早期阶段的识别和预测中的作用 肺纤维化（PF），根据肺成像确定为间质性肺异常（ILA）。PES-3 将评估压力驱动的表观遗传年龄加速和变性成年人的炎症。

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.