Role of periostin expressing cells in intramembranous bone regeneration

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Project Summary/Abstract: The proposal includes a comprehensive 5-year mentored career development plan for Dr. Frank Ko to transition to an independent investigator who studies intramembranous bone regeneration. The candidate is currently an assistant professor in the Department of Cell & Molecular Medicine (CMM) at Rush University Medical Center (RUMC) and conducts his research at RUMC and at its affiliated centers and institutions. He is well supported by the institution and will devote 100% of his time to his research and career development plan. The candidate has assembled mentors and a scientific advisory committee with a wide array of complementary expertise and extensive mentoring experience to offer career guidance during his transition to independent research and train him in new intellectual and technical skills for his proposed studies. His mentor, Dr. Rick Sumner, is an expert in the field of bone regeneration and implant fixation, the Chair of CMM at RUMC, and the director of Rush MicroCT/Histology Core Facility. His co-mentor, Dr. Anna Spagnoli, is a clinician-scientist with an expertise in the field of skeletal development and diseases and is the director of Section of Molecular Medicine in the Department of Orthopedic Surgery at RUMC. Scientific advisory committee member Dr. Noriaki Ono is a molecular biologist studying skeletal stem and progenitor cells. The science focuses on the role of periostin-expressing cells in intramembranous bone regeneration following marrow ablation surgery. The candidate discovered that these cells, which are normally absent in marrow and reside in the periosteum, are present in the regenerating marrow cavity following the surgery and their depletion delays intramembranous bone regeneration. Thus, the specific aims are to investigate: 1) the necessity of periostin-expressing cells and periostin in intramembranous bone regeneration; and 2) the lineage commitment, molecular signatures, and differentiation of periostin-expressing cells and their progeny during intramembranous bone regeneration. To complement his prior training in bone biomechanics and molecular biology in intact tissues, the candidate will be trained in the use of reporter mice, animal surgery, and regenerated bone phenotyping, including light sheet and expansion microscopy, gene and protein expression analyses, and in vitro culture and assay. Further, he will participate in career development activities that include didactic lectures and seminar series focusing on tissue regeneration, stem cell biology, biostatistics, grant writing, responsible conduct of research, and scientific presentation. This K01 proposal will allow the candidate to gain valuable career development mentoring to achieve his goal of becoming an independent investigator studying intramembranous bone regeneration.