Spatialomics and quantitative MRI of ischemic injury in a piglet model of Legg-Calve-Perthes disease

Legg-Calve-Perthes 病仔猪模型缺血性损伤的空间组学和定量 MRI

• 批准号: 10806492
• 负责人: Alexandra PR Armstrong
• 金额: $ 13.24万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2028-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10806492
• 关键词: Acute; Address; Adult; Affect; Animal Model; Appearance; Appointment; Attention; Automobile Driving; Bilateral; Biological Markers; Biological Process; Biology; Cartilage; Cartilage injury; Cell Maturation; Characteristics; Child; Child Care; Child Health; Childhood; Chondrocytes; Clinical; Clinical Management; Clinical Sciences; Complication; Consensus; Contralateral; Data; Dedications; Development; Diagnostic Procedure; Disease; Disease Progression; Disease model; Doctor of Philosophy; Down-Regulation; Early Diagnosis; Educational process of instructing; Educational workshop; Epiphysial cartilage; Evidence based treatment; Faculty; Family suidae; Femur; Foundations; Functional disorder; Funding; Gene Expression; Gene Expression Profile; Genes; Genetic Transcription; Genomics; Goals; Growth; Hemorrhage; Hip region structure; Histologic; Histology; Imaging Techniques; Injury; Intervention; Ischemia; Knowledge; Leadership; Learning; Leg; Legg-Perthes Disease; Length; Magnetic Resonance Imaging; Measures; Mentored Research Scientist Development Award; Mentors; Methods; Microscopic; Molecular; Morphology; Musculoskeletal; Neck; Operative Surgical Procedures; Orthopedic Surgery; Orthopedics; Outcome; Pain; Pathogenesis; Pathology; Pathway interactions; Patients; Pattern; Perfusion; Physiologic Ossification; Positioning Attribute; Recovery; Relaxation; Research; Research Personnel; Rheumatology; Role; Secondary to; Signal Transduction; Site; Surface; Surgeon; Techniques; Thick; Time; Tissues; Training; Transforming Growth Factor beta; Treatment Protocols; Uncertainty; Up-Regulation; Vascular blood supply; Work; candidate marker; career; cartilage repair; clinical care; diagnostic signature; differential expression; effective therapy; experience; femur head; genetic signature; genomic data; high risk; improved; insight; ischemic injury; knowledge base; medical specialties; member; musculoskeletal imaging; novel; porcine model; preservation; prevent; programs; radiological imaging; repaired; response; symposium; tenure track; therapeutic target; transcriptomics; translational potential

PROJECT SUMMARY This K01 award will provide training and protected research time for Alexandra Armstrong, DVM, DACVP, PhD to achieve her career goal of becoming an independently-funded investigator with specialty expertise in animal models of developmental orthopedic diseases, including the application of spatialomic profiling and quantitative magnetic resonance imaging (MRI) techniques. Legg-Calvé-Perthes disease (LCPD) is a developmental orthopaedic disease with uncertainty regarding its pathogenesis or the ideal treatment regimen. Importantly, a key aspect of the pathogenesis is ischemic injury to the growth cartilage in the proximal femur: both the epiphyseal growth cartilage, underlying the articular surface, and the growth plate cartilage, within the femoral neck. Dysfunction of these growth cartilages can contribute to collapse of the femoral head and to growth arrest and leg length discrepancies, respectively. Despite the known role of ischemic injury to cartilage in LCPD, little attention has been paid to the contribution of growth cartilage to either recovery or disease progression. To address this critical gap, Dr. Armstrong will use a well-validated piglet model of LCPD to identify differentially expressed genes within the growth cartilage associated with growth disturbances (Aim 1) and the response of the growth plate and epiphyseal cartilage to transphyseal drilling (Aim 2), a treatment that may benefit children with LCPD-induced growth disturbances. The patterns and pathways identified by spatialomics profiling will be correlated with the histological features and compared to the quantitative MRI features of the epiphyseal cartilage, with the potential to identify translational biomarkers of growth cartilage injury. Dr. Armstrong has a strong scientific foundation, including expertise in musculoskeletal pathology, but she requires additional training and dedicated time to develop her orthopaedic research program addressing questions of pathogenesis of pediatric orthopaedic diseases using animal models. During the five-year training period, she will gain knowledge in the clinical management of developmental orthopaedic disorders, develop expertise in novel spatialomics methods and analysis, develop a strong knowledge base in cutting-edge musculoskeletal MRI techniques, gain crucial experience in grantwriting, and undergo professional development in diversity, mentoring, teaching, and leadership that will benefit her as a tenure-track faculty member with a primarily research-focused appointment. This training will culminate in Dr. Armstrong achieving R01 or equivalent funding. She will be mentored by leading experts in animal models, orthopaedic surgery, musculoskeletal imaging, rheumatology, and pathology, along with didactic training in the analysis of genomic data, hands-on experiences, seminars/workshops, and conferences. Dr. Armstrong’s work will be centered on the UMN Veterinary Clinical Sciences department, where three of her four mentors are situated. Dr. Armstrong’s K01 training will fully prepare her to launch an independent research career focused on improving the health of children affected by pediatric orthopaedic diseases.

项目摘要 该K01奖将为Alexandra Armstrong，DVM，DACVP，PhD提供培训和受保护的研究时间 为了实现她成为拥有动物专业专业知识的独立资助的调查员的职业目标 发生骨科疾病的模型，包括应用空间分析和定量的应用 磁共振成像（MRI）技术。 legg-calvé-珀斯病（LCPD）是一种发育 关于其发病机理或理想治疗方案的骨科疾病。重要的是， 发病机理的关键方面是股骨近端生长软骨的缺血性损伤：既 骨骨表面和生长板软骨的基础性骨膜生长软骨在股骨内部 脖子。这些生长软骨功能障碍可能导致股骨头崩溃并捕捉逮捕 和腿长差异分别差异。尽管已知缺血性软骨在LCPD中的作用，但很少 已经注意了软骨对恢复或疾病进展的贡献。到 解决这个关键的差距，阿姆斯特朗博士将使用验证良好的LCPD仔猪模型来识别不同的识别 与生长灾害相关的生长软骨（AIM 1）和反应的生长软骨内的基因 生长板和外周期软骨到遗传钻孔（AIM 2），这种治疗可能使儿童受益 LCPD诱导的生长障碍。通过空间分析确定的模式和途径将是 与组织学特征相关，并将其与骨epiphyseal的定量MRI特征进行比较 软骨，有可能鉴定生长软骨损伤的转化生物标志物。阿姆斯特朗博士有一个 强大的科学基础，包括肌肉骨骼病理学的专业知识，但她需要额外的培训 并专门开发她的骨科研究计划，以解决有关的发病机理的问题 使用动物模型的小儿骨科疾病。在五年的培训期间，她将获得知识 在发育骨科疾病的临床管理中，发展新型时尚学方面的专业知识 方法和分析，在尖端的肌肉骨骼MRI技术中发展有很强的知识基础，增益 在授予写作和经历多样性，心理，教学和经历专业发展方面的重要经验 领导力将使她成为终身轨道的教职员工，并以主要的研究为中心的任命。 这项培训将在阿姆斯特朗博士获得R01或同等资金中达到高潮。她将通过领导来修补 沿着动物模型，骨科手术，肌肉骨骼成像，风湿病学和病理学专家 通过分析基因组数据，动手体验，半手/讲习班和 会议。阿姆斯特朗博士的工作将集中在UMN兽医临床科学系，那里 她的四位导师中有三名位于位置。 Armstrong博士的K01培训将为她做好准备，以启动独立 研究职业的重点是改善受小儿骨科疾病影响的儿童的健康。