The overall goal of the Pilot/Exploratory Studies Core (PESC) is to support and facilitate innovative and rigor- ous research that will enhance our understanding of the etiology, pathogenesis, diagnosis, prevention, conse- quences, and management of multifactorial geriatric conditions (the focus of the Yale OAIC), leading ultimately to the development of interventions to increase or maintain independence in older persons. The Leader of the PESC, Dr. Albert Shaw, is nationally recognized for his research on aging of the human immune system. He holds a K24 award from the NIA focused on immunosenescence, is MPI of the Yale Infectious Diseases NIH training grant, and is the current chair of a standing NIH study section on vaccines. These activities give him an exceptional overview of aging research. Dr. Shaw will work closely with the Co-Leader of the PESC, Dr. Terri Fried, a leader in research on clinical decision-making in older persons. The Specific Aims of the PESC are to: (1) solicit and select the most meritorious research proposals for PESC funding; (2) provide investigators of PESC studies with access to resources from the Operations (RC1) and Biostatistics (RC2) Cores; (3) facilitate potential opportunities for collaboration among PESC investigators; (4) monitor the progress of PESC studies; (5) facilitate development of PESC studies into independently funded grant applications; and (6) ensure the safety and protection of human subjects and vertebrate animals enrolled in PESC studies. In addition to one- year $40,000 pilot/exploratory studies (PESs), we will continue an Expedited Pilot (EXPI) grant program, which will fund small grants (capped at $5000) that are awarded within 4 weeks. These grants are intended for re- search activities in which a rapid infusion of a relatively small amount of funds will facilitate a successful extra- mural grant application. PESs and EXPI awards will take full advantage of the resources and expertise availa- ble from the OAIC’s two Resource Cores. Priority for PESC funding will be given to early-stage investigators who are transitioning to independence, including the growing number of prior REC Scholars. By facilitating ac- cess to the OAIC research infrastructure, these PESC awards will continue to foster the development of exter- nal grants that will advance our understanding of multifactorial geriatric conditions. During the current funding cycle, the PESC invested $625,000 (total costs) that has resulted, to date, in 92 publications and $14.6 million in extramural funding (total costs). During Year 1 of the next cycle, three innovative PESs will be supported from early-stage physician scientists: PES-1—Age-associated alterations in NLRP3 inflammasome function in the setting of COVID-19 (PI, Heidi Zapata, MD, PhD); PES-2—Evaluating short-term outcomes of surveillance mammography among older women with a history of breast cancer (PI, Ilana Richman, MD, MHS); and PES- 3—Transcriptomic signatures of microgl...