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.
