Our Department’s basic and translational research program has a clear and direct mission to produce new treatments for a variety of ailments affecting the musculoskeletal system. We have orthopaedic research laboratories operating at Parnassus Heights, San Francisco General Hospital, and the VA Medical Center. Please contact individual labs to learn more about opportunities for participating in or supporting our research efforts.
Our major areas of expertise and investigation include:
Ongoing Research Projects
- Genomic Response During Fracture Repair:
This research uses cDNA microarray approaches to allow a rapid understanding of gene and gene regulatory networks that are responsible for bone repair thereby aiding in the design of more comprehensive, gene-targeted therapies for fracture repair.
- Effects of Age on Bone Healing: This project identifies genetic and physiological factors compromising the healing process of older individuals using a mouse model. A goal is to develop molecular strategies to restore an older animal's ability to heal skeletal injuries.
- The Role of Vascularization During Bone Repair: This work examines molecular, cellular, and physiological events that are associated with revascularization of injured bone. A goal is to design novel therapeutic strategies to enhance revascularization and bone regeneration.
- Therapeutic Loading of the Intervertebral Disc: This research characterizes a disc-loading regimen that optimizes disc health. Using a combination of mathematical models and a dynamic in vivo mouse model, this research will define a therapeutic loading regimen for the intervertebral disc.
- Tissue Biomechanics: This research is focused on developing structure/function relationships for musculoskeletal tissues. The goal is to define dependencies between extracellular matrix content and organization and mechanical function. These relationships will provide the basis for clarifying disease etiology as well as defining targets for therapeutic intervention.
- Biomechanics of Orthopaedic Implants: Studies are being conducted to characterize biomechanical features of novel devices used in a number of orthopaedic applications. For example, cadaveric models are employed to quantify the efficacy of total disc replacement implants toward restoring spine kinematics. Experimental biomechanics is also being used to characterize and optimize external fixation devices for stabilizing long-bone fractures.
- Intervertebral Disc Repair with Mesenchymal Stem Cells: This project tests the ability of bone marrow-derived stem cells to differentiate within the environment of the intervertebral disc and to participate during remodeling and repair. A goal is to produce new techniques for treating degenerated and/or injured discs in humans.
- Molecular Mechanisms Regulating Mineralization: This research focuses on molecular signaling pathways regulating the mineralization of osteoblasts derived from embryonic mesenchymal stem cells. A goal is to develop novel therapeutic approaches for inducing bone mineralization following disease or injury.
- Mesenchymal Stem Cells and Skeletogenesis: This work identifies developmental mechanisms through which mesenchymal stem cells acquire spatiotemporal patterning information during the development of the skeleton. A goal is to utilize various molecules to control when, where, and in what size and shape stem cells differentiate into cartilage and bone.
- Mesenchymal Stem Cells and Mechanoplasticity: This project examines the potential of stem cells in musculoskeletal tissue engineering as a means to regenerate matrix structure and function. A goal is to define mechanical receptiveness of stem cells as a function of differentiation stage, and to develop techniques for patterning tissues using mechanical cues.
- Molecular and Cellular Mechanisms of Secondary Injury Cascades Following Trauma: This research investigates mechanisms involved in programmed cell death following acute trauma involving articular cartilage and the spinal cord. Interventions designed to limit programmed cell death in these tissues may form the basis of future therapeutic strategies for facilitating skeletal tissue regeneration.
- Mouse Disk Regeneration by Injection: This project seeks to increase cell proliferation and matrix synthesis in degenerated disc by injecting growth factors such as Fibroblast Growth Factors (FGF) into the nucleus of mouse tail discs which have undergone compression and degeneration. A goal is to understand the effects of injected growth factors and stem cells in a mouse model in order to aid in the development of effective treatments for humans with degenerated disks.
- Animal Models of Disc Degeneration and Low Back Pain: Because disc degeneration is an evolving process in vivo, animal models are necessary to clarify degeneration mechanisms as well as to study novel clinical interventions. Several systems have been developed and characterized via a series of outcome measures that include: biomechanics, imaging, cell biology, and tissue morphology.
- BMP Signaling and the Generation of Cartilage and Bone: This research employs various approaches to manipulate the activity of Bone Morphogenetic Proteins (BMP) during development of the skeleton. A goal is to test the therapeutic potential of these growth factors to stimulate bone and/or cartilage formation in vivo.
- Molecular and Cellular Mechanisms Controlling Intramembranous Ossification: This project defines signaling pathways and tissue interactions required for intramembranous ossification. A goal is to identify molecular processes that can re-initiate intramembranous ossification in cases of skeletal disease or trauma.
- Molecular and Cellular Mechanisms Controlling Musculoskeletal Integration: This study investigates developmental mechanisms through which skeletal and muscular precursor populations achieve their proper size, shape, orientation, and functional integration. Such information will be critical for devising molecular-based therapies that can induce repair and regeneration of anatomical complexes affected by congenital defects, disease, and trauma.
- Tissue Engineering of Fibrocartilage: This project identifies the mechanical and biologic environment necessary to produce the extracellular matrix found in hydrated soft tissues such as temporomandibular joint (TMJ) and intervertebral disc. A goal is to design interventions for arthritis including clinical interventions and development of tissue engineered constructs for implantation.
