The James Laboratory is located in the Department of Pathology in the Johns Hopkins University School of Medicine. Our research focus lies at the intersection of bone pathophysiology and stem cell biology. Current subjects of study include bone repair and regeneration, osteoprogenitor cell characterization and use, and neoplastic bone. A partial description of current interests is presented below:
Perivascular progenitor cells
Perivascular stem cells induce ectopic bone formation. MicroCT reconstructions (left) and axial cross-sectional images (right) of ectopic bone after perivascular stem cell implantation.
Once considered a simple regulator of blood flow, it is clear that the vascular wall houses a wealth of resident progenitor or stem cells. Multipotent mesenchymal progenitors are able to be identified in situ or purified and applied for tissue regeneration purposes. See below for several links to publications.
- Human perivascular stem cell-derived extracellular vesicles mediate bone repair.
- Comparison of Human Tissue Microarray to Human Pericyte Transcriptome Yields Novel Perivascular Cell Markers
- Perivascular Mesenchymal Progenitors for Bone Regeneration.
- Relative contributions of adipose-resident CD146+ pericytes and CD34+ adventitial progenitor cells in bone tissue engineering.
Neural influence on bone formation and repair
Nerve and vessel patterning within a healing bone after stress fracture in a mouse. Nerves appear green (Thy1-YFP), vessels appear red (CD31). Dashed lines indicate the upper and lower bounds of the fracture callus, with high magnification images to the right. Fracture sites are indicated by arrowheads.
Skeletal sensory nerves are abundant in mature bone tissue, but their role in mammalian bone morphogenesis and repair is poorly understood. Our group studies the role of skeletal sensory nerves, focusing on understanding the crosstalk between peripheral nerves and bone-forming cells during tissue repair. Recently we have shown that NGF (Nerve growth factor) responsive TrkA (Tropomyosin receptor kinase A)-expressing sensory nerve fibers are integral for stress fracture healing in the mouse skeleton.
Novel differentiation factors for bone repair
Colorized micro computed tomography (microCT) reconstruction of a mouse calvarial defect model. On the right, the original and unhealed parietal bone defect site can be visualized in blue. On the left, partial bone defect healing is observed in white.
Numerous growth and differentiation factors are produced or released from bone after injury, some of which aid in the reparative process. We have shown that exogenous application of positive regulators of Hedgehog and Wnt signaling induce bone healing in both calvarial, axial, and appendicular skeleton. See below for several links to publications.
- Calvarial Defect Healing Induced by Small Molecule Smoothened Agonist
- Vertebral Implantation of NELL-1 Enhances Bone Formation in an Osteoporotic Sheep Model
- Novel Wnt Regulator NEL-Like Molecule-1 Antagonizes Adipogenesis and Augments Osteogenesis Induced by Bone Morphogenetic Protein 2
- NELL-1 in the treatment of osteoporotic bone loss
- Combining Smoothened Agonist (SAG) and NEL-like protein-1 (NELL-1) Enhances Bone Healing
Bone and soft tissue tumors
The wide histologic spectrum of osteosarcoma.
Malignant tumors of mesenchymal origin are a complex and heterogeneous group of aggressive tumors, termed sarcomas. Our group is most interested in skeletal sarcomas (osteosarcoma and chondrosarcoma), and perivascular soft tissue tumors. See below for several links to publications.
- Vascular patterning in human heterotopic ossification
- Sclerostin expression in skeletal sarcomas
- NELL-1 expression in benign and malignant bone tumors
- Pericytic mimicry in well-differentiated liposarcoma/atypical lipomatous tumor
- The pericyte antigen RGS5 in perivascular soft tissue tumors
- Ang-2 but not Ang-1 expression in perivascular soft tissue tumors