Basic Research
Center for Pediatric Bone Biology and Translational Research
Working with Scottish Rite for Children patients and their doctors, scientists in the Center for Pediatric Bone Biology and Translational Research work to discover the underlying causes of poorly understood musculoskeletal disorders in children, and to understand the fundamental steps that lead to disease. In parallel, we work with clinicians to translate this knowledge into new treatments and improved diagnoses. The Center works in close partnership with the University of Texas Southwestern Medical Center and collaboration with many investigators around the world. Center laboratories are located on both the Scottish Rite for Children Dallas Campus and on the UT Southwestern South Campus.
Divisions & Laboratories
Molecular Genetics
Principal Investigators
Carol A. Wise, Ph.D., DirectorJonathan Rios, Ph.D., Co-director
We work with clinicians to identify unsolved and problematic pediatric musculoskeletal disorders. Our laboratory uses high throughput genomics, cell-based assays, and transgenic animal models to define underlying disease mechanisms that will enlighten improved treatments. Major areas of investigation include:
- Developmental Mechanisms of Idiopathic Scoliosis: This program, funded by the National Institutes of Health, is a collaboration with Dr. Lila Solnica-Krezel, Washington University in St. Louis, and Dr. Nadav Ahituv, University of California, San Francisco.
- Fracture healing defects (pseudarthrosis): SRC scientists within the Division of Molecular Genetics have discovered genetic causes of persistent fracture pseudarthroses that occur in children. Using high-throughput molecular techniques, including single-cell sequencing, we are dissecting the role that skeletal stem cells play in fracture repair and are understanding how these genetic alterations lead to persistent fractures. Using a variety of techniques, we are identifying and testing novel treatment strategies to improve fracture healing in these patients.
- G.O.O.D. (Genomics of Orthopaedic Disorders) for Kids Program: This program uses state-of-the-art methods to discover genetic causes of rare musculoskeletal disorders. G.O.O.D. for Kids focuses on rare conditions that are often unstudied and remain undiagnosed. The success of this Program stems from the unique collaboration between SRC orthopaedic surgeons and research personnel within the Division of Molecular Genetics.
- Pre-clinical model development: As part of the UT Southwestern Mutagenetix saturation mutagenesis screen in mice (mutagenetix.utsouthwestern.edu), we are identifying and characterizing novel pre-clinical mouse models of human disease. By integrating these pre-clinical models with ongoing human clinical and research sequencing projects, we are discovering novel human genetic diseases. These pre-clinical models also enable translational studies focused on the development and testing of novel therapies for these and related conditions.
Tissue Repair and Regeneration
Principal Investigator
Harry Kim, M.D., M.S., F.R.C.S.C. Our lab is leading the development of new treatment strategies for femoral head osteonecrosis and Legg-Calvé-Perthes disease through basic and translational research. Current areas of investigation include:
- Elucidating molecular mechanisms leading to chronic inflammation and poor bone healing response (increased bone resorption and decreased new bone formation) following femoral head osteonecrosis.
- Development of novel tissue engineering methods to recondition and revitalize the necrotic femoral head.
- Determining the efficacy of pharmaceutical agents that block interleukin-6 receptor, toll-like receptor-4 and bone resorption for the treatment of femoral head osteonecrosis.
- Development of advanced MRI for early detection, assessment and follow-up of femoral head osteonecrosis.
Pediatric Musculoskeletal Infection
Principal Investigator
Lawson Copley, M.D.We study the genomic and virulence factors that cause deep and severely debilitating musculoskeletal infections in children. Major areas of investigation include:
- Identifying gene expression signatures that correlate with disease severity in children with acute hematogenous osteomyelitis
- Identifying genomic virulence determinants of Staphylococcus aureus
- Leading collaborative studies to establish a mouse model of acute hematogenous osteomyelitis
- Defining the bacterial gene expression patterns during the pathogenesis of the infection
- Investigating cellular effects (hemolysis, neutrophil killing, endothelial uptake or collagen adhesion) of Staphylococcus aureus as a function of virulence capability of the specific isolate
Core Facilities
The Center is supported by two core facilities, Cellular Pathology and the Scottish Rite for Children Biobanking Service.
Scottish Rite for Children Biobanking Service
The Scottish Rite for Children Biobanking service is a centralized resource for collecting, processing, storing and distributing annotated biospecimens and their derivatives for research purposes. Collection services include procuring samples in coordination with Scottish Rite for Children surgical teams and researchers, annotation with unique identifiers, logging into a centralized database and storage. Processing serves include tissue embedding, cell culture, DNA isolation and freezing. Samples are stored in the Cellular Pathology laboratory and distributed upon request and approval of the Biobank Oversight Committee.
Cellular Pathology
Cellular pathology services are provided for the processing of clinical neuromuscular, orthopedic diagnostic biopsies. Tissue specimens are also processed for research projects. Specimens including soft and hard tissues, blood and other body fluids are handled. The following procedures are offered as a service for all tissue samples:
- Routine Histology
- Rapid Frozen Section
- Immunocytochemistry
- Image Analysis
- Hard Tissue Techniques
- Tissue Banking
- Send outs
Scottish Rite for Children Biobanking Service
The Scottish Rite for Children Biobanking service is a centralized resource for collecting, processing, storing and distributing annotated biospecimens and their derivatives for research purposes. Collection services include procuring samples in coordination with Scottish Rite for Children surgical teams and researchers, annotation with unique identifiers, logging into a centralized database and storage. Processing serves include tissue embedding, cell culture, DNA isolation and freezing. Samples are stored in the Cellular Pathology laboratory and distributed upon request and approval of the Biobank Oversight Committee.
