Chuanju Liu, PhD

Professor; Departments of Orthopaedic Surgery (Ortho-Research) and Cell Biology

Liu Lab

Cell Biology

cartilage metabolism and arthritis, molecular biology of skeletal development, interferon and cytokine action, structure, function and pharmacology of ion channels, musculoskeletal tumors



Contact Information

301 East 17th Street
NYU Hospital for Joint Diseases
Floor 16, Room 1608
New York, NY 10003

Tel: 212-598-6103

Research Summary

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 the imbalance between inflammatory cytokines and their antagonists. The discovery of matrix-degrading enzymes and the inhibitors that antagonize the actions of cytokines are therefore important from both a pathophysiologic and a therapeutic standpoint. Our studies led to the identification of ADAMTS-7 and ADAMTS-12 as two metalloproteinases associated with the cartilage and the pathogenesis of arthritis. Our first research focus is to investigate the roles of ADAMTS metalloproteinase in the joint development and arthritic diseases. We hope to increase our ability to monitor the biological and physical properties of cartilage extracellular matrix as they become altered by various disease processes, and ultimately to develop effective therapeutic strategies for arthritis, such as blocking enzymatic agents.

Alongside our investigation into the role of ADAMTS, we have also turned our attention on progranulin (PGRN), an autocrine growth factor with multiple functions, as PGRN was originally isolated as both a chondrogenic and an OA-related growth factor. In addition, we also identified PGRN as a binding partner of TNF receptors (TNFR). Armed with this knowledge, we focused on the therapeutic potential of PGRN by identifying the exact domains that interacted with TNFR, which led to the discovery of an engineered protein, termed ‘antagonist of TNF-TNFR signalling via targeting to TNF receptors’ – Atstrrin for short. Atsttrin inhibited TNF-mediated inflammatory pathways and thus suppressed disease progression in several inflammatory animal models. Thus, our second focus is to investigate the roles of PGRN and its derivatives in the pathogenesis of both arthritis and inflammatory autoimmune diseases, with the goal of developing new interventions for various degenerative and inflammatory diseases and conditions by utilizing PGRN and/or its derivatives, with the special focus on Atsttrin.

Interferons (IFNs) are cytokines with multiple biological activities whose actions are realized via numerous INF-inducible molecules. Our studies of interferon-inducible p200 family proteins, with a special focus on p204, revealed that the proteins of this family are important regulators of cell proliferation, differentiation and interferon activity. Deregulation of these proteins is linked to various diseases, such as immune, inflammation and tumor-related conditions. Recently, p204/IFI16 was isolated to be a cytoplasmic DNA sensor that induces the transcription of genes involved in the innate immune response, including TNFα/β. In addition, it also has the capacity to form an inflammasome within the nucleus and to sense viral DNA in this location. Our third research focus is to continue our current studies of the physiological and pathological roles of interferon-inducible proteins as well as the cellular and molecular mechanisms involved.