Myogenic Mechanisms of Craniofacial Skeletal Muscle Regeneration

颅面骨骼肌再生的生肌机制

• 批准号: 10283418
• 负责人: Lauren Katz McKay
• 金额: $ 17万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 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/10283418
• 关键词: Affect; Appearance; Basic Science; Biological Assay; Biology; Birth; Breathing; Cell Separation; Cell Transplantation; Cell physiology; Cells; Cellular Assay; Clinical; Data; Data Analyses; Defect; Deglutition; Development; Discipline; Disease; Eating; Environment; Excision; Face; Facial asymmetry; Foundations; Gene Expression Profile; Genes; Genomics; Goals; Impairment; In Vitro; Individual; Injury; Investigation; K-Series Research Career Programs; Knock-out; Knowledge; Lentivirus Vector; Life; Limb structure; Literature; Malignant Neoplasms; Manuscripts; Masseter Muscle; Mastication; Mediating; Mentors; Mentorship; Methodology; Modality; Modeling; Molecular; Molecular Target; Muscle; Muscle Fibers; Muscle function; Muscle satellite cell; Muscular Dystrophies; Myopathy; Natural regeneration; Oral; Patients; Phenotype; Population; Preparation; Quality of life; Regenerative Medicine; Regenerative capacity; Regulation; Research; Role; Scientist; Skeletal Muscle; Stem cell transplant; Techniques; Technology; Testing; Therapeutic; Time; Tissue-Specific Gene Expression; Tissues; Training; Trauma; Viral; base; career; craniofacial; craniofacial disorder; differential expression; effective therapy; experimental study; genetic manipulation; in vivo; in vivo Model; molecular phenotype; multidisciplinary; muscle regeneration; myogenesis; negative affect; novel; novel strategies; oral biology; orofacial; programs; regeneration potential; regenerative; response to injury; restoration; satellite cell; single-cell RNA sequencing; skeletal; skills; stem; stem cell population; stem cell self renewal; stem cells; tissue regeneration; tumor

ABSTRACT This application is for a Mentored Clinical Scientist Research Career Development Award (K08) for Dr. Lauren Katz. She is currently conducting research on craniofacial skeletal muscle and has observed that this muscle type has a unique regenerative program compared to muscles of the limb and trunk. This K08 will enhance Dr. Katz's ability to 1) become an expert in craniofacial muscle stem cells and regeneration, 2) conduct basic science research at the highest level in a tissue rarely studied, 3) acquire cutting-edge skills in stem cell techniques including single-cell RNA sequencing (scRNA-seq) and ex vivo cell transplantation, 4) gain skills in proposal development, manuscript preparation, and data presentation, and 5) develop a high-quality independent research program that will allow for collaborative opportunities with scientists and clinicians from across disciplines. To achieve these goals, Dr. Katz has devised a clear and focused training plan and has identified individuals who are experts in the aforementioned disciplines. Her multidisciplinary mentoring team consists of: Drs. James White (basic scientist, skeletal muscle regeneration and stem cells), William Maixner (clinician-scientist, oral and craniofacial research), Shannon Wallet (basic scientist, oral and craniofacial research), Elisabeth Barton (basic scientist, skeletal muscle regeneration), Kevin Byrd (clinician-scientist, oral stem cells), Lyndon Cooper (clinician-scientist, oral stem cells), Eric Everett (basic scientist, oral biology), Jimena Giudice (basic scientist, skeletal muscle research), and Simon Gregory (basic scientist, scRNA-seq). There exists a clinical need to rebuild functional craniofacial muscle in patients suffering from certain diseases (muscular dystrophy, hemifacial microsomia), facial trauma, and tumor resections. The lack of a comprehensive investigation of the craniofacial musculature and its stem population has resulted in a poor understanding of the regenerative capacity of this tissue when faced with disease or trauma. Our current knowledge of skeletal muscles and their stem cell populations comes from the limb muscles; however, it is known that distinct differences in embryological origin exist between muscles of the limb and those of the craniofacial region. Therefore, the objectives of this study are to use injury models to elucidate the in vivo regenerative capacity of craniofacial skeletal muscle and to perform deep phenotyping on isolated craniofacial satellite cells to identify molecular targets specific to craniofacial muscle regeneration. Regenerative capacity will be assessed using in vivo models of muscle regeneration and in vitro cellular function assays (Aim 1). scRNA-seq and ex vivo stem cell transplantation will be utilized to identify craniofacial muscle-specific regulators of myogenesis (Aim 2) and identified targets will be investigated using lentiviral vectors and knockout models (Aim 3). Together, the K08 training and mentorship will enable Dr. Katz to transition into an independent research career and become a leader in the field of craniofacial muscle regenerative medicine and translational therapeutics.

摘要