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.

项目总结