The northern New England region constitutes a unique public health landscape with challenging needs for its residents, particularly prevention, early detection, and intervention of chronic diseases. The Pilot Projects Program (PPP) successfully provided support to clinical and translational investigators to conduct public health research on chronic diseases in the region. The PPP worked with all the NNE-CTR Cores over the first four years to develop and implement 29 projects with clinical and translational implications. Those pilots enhanced healthcare delivery as well as accelerated the career trajectory of several pilot project awardees. Building upon our considerable accomplishments, the current aims of the PPP will support a three-step process to enhance further pilot success while simultaneously improving our mentoring program in collaboration with the Professional Development Core. In Aim 1 of this three-stage process, we will expand researcher recruitment and support concept development to incentivize and build meaningful interdisciplinary collaborations. We will disseminate PPP opportunities through our NNE-CTR website, newsletter, and social media, and support young, early-stage and established investigators during concept development in collaboration with the Professional Development (PDC) and the Biostatistics, Epidemiology, and Research Design (BERD) Cores. In Aim 2, we will help investigators prepare Pilot Project applications by providing mentorship in study design and data analysis, and by engaging navigators from the Community Engagement and Outreach (CEO), PDC, and BERD Cores. We will encourage consultation with Core leadership, community representatives, and content experts to enhance design feasibility. In the final stage, Aim 3, we will mentor pilot project awardees during the post-award phase by providing scientific and professional development guidance to awardees via quarterly meetings. We will assist awardees to develop extramural grant proposals, including holding mock “study sections” in partnership with the PDC, to ensure competitive proposals. For those whose external applications fell below the payline, we will return to the first stage and support further concept development for subsequent applications. We will leverage our existing partnerships with CTSAs, State Departments of Health, the Northern New England Practice-Based Research Network, and the Rural Health Communications Network. By restructuring our pilot awards, we will support an array of projects, ranging from multistage clinical and translational studies to community-specific public health initiatives. This should provide pilot awardees with the opportunity to enhance their academic careers while serving the rapidly shifting public health needs of our communities.