Role of periostin expressing cells in intramembranous bone regeneration

骨膜蛋白表达细胞在膜内骨再生中的作用

• 批准号: 10556659
• 负责人: Frank Ko
• 金额: $ 4.59万
• 依托单位: RUSH UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10556659
• 关键词: Ablation; Academic Medical Centers; Address; Advisory Committees; Animals; Biological; Biological Assay; Biomechanics; Biometry; Bone Marrow; Bone Marrow Ablation; Bone Regeneration; Cell Culture Techniques; Cells; Clinical; Committee Members; Complement; Core Facility; Data; Degenerative polyarthritis; Development Plans; Disease; Ensure; Failure; Female; Femur; Gene Expression; Goals; Grant; Health Sciences; Histology; Immunohistochemistry; Impairment; Implant; In Vitro; Institution; Knock-out; Knockout Mice; Lead; Light; Marrow; Mentors; Microscopy; Molecular; Molecular Biology; Molecular Medicine; Molecular Profiling; Mus; Musculoskeletal; Natural regeneration; Operative Surgical Procedures; Orthopedic Procedures; Orthopedic Surgery; Osteoporosis; Outcome; Parents; Pathology; Pathway interactions; Patients; Periosteum; Phenotype; Procedures; Publishing; Recovery; Reporter; Research; Research Personnel; Research Training; Role; Sample Size; Science; Scientist; Series; Skeletal Development; Technical Expertise; Therapeutic; Time; Tissues; Training; Vocational Guidance; WNT Signaling Pathway; Women' s Health; Work; Writing; bone; bone fracture repair; bone mass; career development; experience; intramembranous bone; knock-down; lectures; male; microCT; novel; osteogenic; parent grant; periostin; professor; protein expression; research and development; response; responsible research conduct; sample fixation; sex; sexual dimorphism; skeletal disorder; skeletal stem cell; stem cell biology; stem cells; tissue regeneration; tomography

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.

项目摘要/摘要：该提案包括全面的5年指导职业发展 计划弗兰克·KO博士过渡到研究膜内骨骼的独立研究者 再生。该候选人目前是细胞与分子医学系的助理教授 （CMM）在拉什大学医学中心（RUMC），并在RUMC进行研究及其隶属关系 中心和机构。他得到了该机构的良好支持，并将100％的时间投入研究 和职业发展计划。候选人已与 各种各样的补充专业知识和广泛的指导经验，以提供职业指导 他向独立研究的过渡，并培训他的新知识和技术技能 研究。他的导师里克·萨姆纳（Rick Sumner）博士是骨骼再生和植入物领域的专家 RUMC的CMM主席，以及Rush Microct/Histomology核心设施的主任。他的院长安娜博士 Spagnoli是一位临床医生科学家，在骨骼发育和疾病领域具有专业知识，是 RUMC骨科手术系分子医学部门主任。科学 咨询委员会成员Noriaki Ono博士是研究骨骼茎和祖细胞的分子生物学家 细胞。科学侧重于表达骨膜素细胞在膜内骨再生中的作用 术后骨髓消融手术。候选人发现这些细胞通常在 骨髓和居住在骨膜中，在手术后的再生骨髓腔中存在 它们的耗竭延迟了膜内骨再生。因此，具体目的是调查：1） 在膜内再生中表达骨膜素的细胞和骨膜素的必要性； 2）血统 在表达骨膜素细胞及其后代的承诺，分子特征和分化 膜内骨再生。补充他先前在骨生物力学和分子方面的培训 完整组织中的生物学，候选人将接受记者小鼠的使用，动物手术和 再生的骨表型，包括光片和膨胀显微镜，基因和蛋白质表达 分析以及体外培养和测定。此外，他将参加职业发展活动 包括教学讲座和研讨会系列，重点是组织再生，干细胞生物学，生物统计学， 赠款写作，负责任的研究和科学介绍。该K01提案将允许 候选人获得宝贵的职业发展指导，以实现成为独立的目标 研究膜内骨再生的研究者。