Pilot and Exploratory Core

试点和探索核心

• 批准号: 10293913
• 负责人: DOUGLAS P. KIEL
• 金额: $ 29.25万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10293913
• 关键词: Acceleration; Adult; Affect; Age; Aging; Animal Model; Applications Grants; Behavior Therapy; Biological Markers; Boston; Capsicum; Cell Aging; Cells; DNA Methylation; Data; Development; Doctor of Philosophy; Elderly; Epigenetic Process; Exposure to; Fibroblasts; Fostering; Funding; Gender; Generations; Impairment; Inflammaging; Inflammation; Inflammatory; Infrastructure; Intellectual Property; Interdisciplinary Study; Interleukin-6; Interstitial Lung Diseases; Intervention; Investigation; Legal patent; Life Cycle Stages; Link; Lung; Lung diseases; Mentorship; Mission; Muscle function; Organ; Organ Transplantation; Outcome; Outcome Study; Participant; Patients; Peer Review; Phenotype; Physical Exercise; Physical Function; Proteomics; Protocols documentation; Psychosocial Stress; Publications; Pulmonary Fibrosis; Request for Applications; Research; Research Personnel; Research Project Grants; Resources; Role; Science; Scientific Advances and Accomplishments; Scientist; Skeletal Muscle; Stress; Testing; Time; Translational Research; Transplantation; base; career; dosage; early life stress; exercise capacity; exercise intervention; follow-up; functional decline; human study; idiopathic pulmonary fibrosis; improved; innovation; interstitial; lung imaging; medical schools; patient stratification; peripheral blood; pre-clinical; programs; psychosocial stressors; randomized trial; response; safety and feasibility; senescence; transgender; translational approach; translational pipeline

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.

摘要 /摘要 波士顿胡椒OAIC的目的是支持一项跨学科研究计划，以促进 促进疗法功能的发展（FPT）。在OAIC的整体任务中，飞行员 探索性研究核心（PESC）将通过飞行员和 探索性研究，提供指导和基础设施核心支持。总体目标 PESC将使早期研究者发起的研究能够获取开发的试点数据 FPT的强大，资金充足且富有成效的翻译研究项目。 PESC的主要目标 在这种续约的背景下 目的是帮助建立与我们的主题保持一致的科学家的职业。目标1意志 继续我们通过提供早期创新和跨学科研究的转化管道 利用我们的波士顿胡椒OAIC核心和基础设施来产生概念证明的资金 临床前数据加快FPT的发展，目标识别的机理研究或 假设建筑物对fpt对骨骼肌肉和身体机能产生影响；和试点测试 人类研究参与者或动物模型的转化干预措施或研究方案，以确保安全， 可行性或确定最佳时间课程或剂量。 AIM 2将促进PESC之间的连通性 研究人员和OAIC资源核心。 AIM 3将催化飞行员和探索性项目成高质量的同行 审查出版物，赠款申请和知识产权/专利。 我们的波士顿胡椒OAIC转向商业委员会选择了三个创新的候选项目 在我们的续约中考虑了PESC支持，从收到的19个申请中的池中 响应广泛宣传的申请请求（RFA）。这三个烛台项目很好 与OAIC的使命保持一致，该使命是通过机制促进FPT的发展，目标 识别，模型生物的概念验证研究，流行病研究和随机试验， 并将受益于使用我们的资源核心。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的作用和次优的结果的假设 来自老年捐助者的移植器官以及早期生活压力影响的表观遗传机制 跨性别者衰老的轨迹。 PES-1评估移植较旧的器官是否启动 衰老细胞通过与衰老相关分泌表型（SASP）连接的衰老细胞的扩散 炎症计划会对老年人的身体机能产生不利影响。 PES-2将检查 衰老相关生物标志物在改善早期识别和预测中的作用 肺纤维化（PF）基于肺成像，被鉴定为间质性肺部异常（ILA）。 PES-3 将评估跨性别成年人表观遗传年龄和炎症的压力驱动的加速度。