Overall Program (L. Liaw PD/PI) MaineHealth Institute for Research initiated a Phase I COBRE in Mesenchymal and Neural Regulation of Metabolic Networks (COBRE in Metabolic Networks) in 2017, directed by Lucy Liaw PhD, Faculty Scientist and Professor at MaineHealth. Our Center in Phase I developed a critical mass of investigators with biomedical research interests in metabolic health and disease, focusing on adipose tissue, bone and skeletal biology, and environmental, neural, and pharmacological inputs that regulate these tissues. Our COBRE also supported three scientific core facilities – Physiology, Histopathology, and Proteomics and Lipidomics cores. These scientific core facilities provide outstanding services, and have responsibility for maintaining state-of-the-art technologies in their respective areas by updating technology, equipment, and maintaining current knowledge. In addition, scientific core facilities are responsible for the training of staff, and assisting in experimental design, project implementation and data analysis. We established a robust mentoring network for our junior investigators, and engaged an external advisory committee to evaluate projects, cores, and our overall Center. Our investment in Phase I COBRE projects and pilot projects thus far has directly yielded six NIH R01 awards (including funding of the original four junior investigator project leads) with seven COBRE members, one NSF CAREER award, one NIH S10 instrumentation grant, and one foundation research grant. Two COBRE members also mentor PhD students who were awarded NIH F31 fellowships during this time. In year four of Phase I, we held a national faculty recruitment that yielded two outstanding new junior investigators who joined our COBRE; one in August 2021 (Matt Lynes PhD), and one in August 2022 (Ziru Li PhD). In addition to Drs. Lynes and Li, Phase II includes support for a third new junior investigator project lead, Dr. Isha Agarwal. These new project leads bring expertise in thermogenic adipocytes, a gut-bone signaling axis, and impact of night shift work on diabetes risk in pregnant women. Our Phase II program will build upon our successful leadership, mentorship and professional development model. We will focus on expanding our portfolio of research and scientific resources under the guidance of an Advisory Committee. Goals for Phase II of this COBRE in Metabolic Networks are: 1) Provide leadership to evolve a robust Center infrastructure including administrative, fiscal and scientific management to support growth of collaborative research and resources in metabolic health and disease, 2) Support career advancement for COBRE investigators and alumni, 3) Maintain high quality shared scientific resources, and 4) Build a diverse research community that is guided by principles of diversity, inclusion, and equity. Successful achievement of these goals will support professional development of promising junior investigators while expanding the use of well-regarded scientific shared research resources, which are already highly utilized by a researcher user base throughout the country.

Narrative This application requests Phase II support for a successful COBRE in Mesenchymal and Neural Regulation of Metabolic Networks. Three new diverse projects study thermogenic adipocytes, gut-bone interactions, and impact of night shift work on diabetes risk in pregnancy, and they will contribute to our knowledge about how to better treat chronic metabolic diseases. Core facilities provide support for Physiology, Histopathology and Microscopy, and Proteomics and Lipidomics.