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INFORMATION FOR

Chuan-Ju Liu, PhD

Charles W. Ohse Professor of Orthopaedics & Rehabilitation

Contact Information

Chuan-Ju Liu, PhD

Office Location

Mailing Address

  • Orthopaedics & Rehabilitation

    P.O. Box 208071

    New Haven, CT 06520-8071

    United States

Research Summary

In the Liu Lab at Yale School of Medicine, our current research interests include 1) musculoskeletal development and disorders, with particular focuses on osteoarthritis and fracture healing; 2) inflammation and autoimmunity, with a special focus on rheumatoid arthritis; and 3) rare genetic lysosomal storage diseases, including Gaucher disease and Tay-Sachs disease.

Extensive Research Description

Arthritis is a degenerative disease that affects more than 66 million individuals in the United States alone. The destruction of the extracellular matrix of cartilage and bone is thought to be mediated by excessive proteolytic activity and an imbalance between inflammatory cytokines and their antagonists. The discovery of matrix-degrading enzymes and the inhibitors that antagonize the actions of cytokines is therefore important from both a pathophysiological and a therapeutic standpoint.

Flow Chart Demonstrating that ADAMTS-7 Plays a Role in the Progression of Osteoarthritis
We discovered that ADAMTS-7 plays a role in COMP degradation in the progression of osteoarthritis.

In the Liu Lab, our studies have led to the identification of ADAMTS-7 and ADAMTS-12 as two metalloproteinases associated with cartilage destabilization and the pathogenesis of arthritis.

In addition to our investigation into the role of ADAMTS, we have turned our attention to progranulin (PGRN), an autocrine growth factor-like molecule with multiple functions, because it was originally isolated as both a chondrogenic and osteoarthritis-related growth factor in our laboratory. Importantly, we also identified PGRN as a binding partner of tumor necrosis factor (TNF) receptors, also known as TNFRs, which are implicated in the regulation of inflammation and autoimmunity.

    Graphic Showing that Tumor Necrosis Factor Receptors are Implicated in the Regulation of Inflammation and Autoimmunity
    Tumor necrosis factor receptors are implicated in the regulation of inflammation and autoimmunity.

    Our primary focus, accordingly, is to further investigate the roles of PGRN in arthritis and autoimmune diseases, in hopes of using PGRN and its derivatives in the development of new interventions for various degenerative and inflammatory conditions.

    Series of Three Microscopic Images Showing that Progranulin is a Factor Involved in Lysosomal Storage Disorders
    We discovered that progranulin is a factor involved in lysosomal storage diseases.

    In our efforts to determine the role of PGRN in lung inflammation, we unexpectedly identified PGRN as a factor involved in Gaucher disease, one of the most common lysosomal storage diseases. Isolation of PGRN as a Gaucher disease modifier provides a foundation for future discoveries relating to this crucial factor in its disease pathogenesis, as well as in uncovering a unique target for developing novel therapies to combat Gaucher disease and probably other lysosomal storage diseases as well.

    Sodium channel Nav1.7, previously believed to be exclusive to neurons, has been identified in chondrocytes. Despite its low density, chondrocyte-expressed Nav1.7 plays a significant role in osteoarthritis progression. Genetic deletion or pharmacological inhibition of Nav1.7 reduced joint damage and alleviated joint pain in various mouse osteoarthritis models. The potential use of existing non-specific Nav blockers or Nav1.7-specific inhibitors represents an unexplored avenue for disease-modifying treatment in osteoarthritis. https://doi.org/10.1038/d41586-023-03845-2


    Coauthors

    Research Interests

    Arthritis, Rheumatoid; Autoimmune Diseases; Bone Regeneration; Cartilage; Inflammation; Musculoskeletal Diseases; Osteoarthritis; Sodium Channels; Lysosomal Storage Diseases; Chondrocytes; Tissue Engineering; Musculoskeletal Development; Fractures, Cartilage; Musculoskeletal Pain

    Selected Publications