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Chuanju Liu

Chuanju Liu, PhD

Professor, Department of Orthopaedic Surgery

Professor, Department of Cell Biology

Keywords
cartilage metabolism and arthritis, skeletal development and diseases, inflammation and immunology, autoimmune diseases, lysosomal storage diseases, structure, function and pharmacology of ion channels
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 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. 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.

One of our research goals is to determine the roles of ADAMTS metalloproteinases in joint development and arthritic diseases. We hope to increase our ability to monitor the biological and physical properties of cartilage extracellular matrix as it becomes altered by various disease processes and, ultimately, to develop effective therapeutic strategies for treating arthritis, such as blocking enzymatic agents.

In addition to our investigation into the role of ADAMTS, we have turned our attention to progranulin (PGRN), an autocrine growth factor with multiple functions, because it was originally isolated as both a chondrogenic and osteoarthritis-related growth factor. Importantly, we identified PGRN as a novel binding partner of tumor necrosis factor (TNF) receptors, also known as TNFRs, which are implicated in the regulation of inflammation and apoptosis. Armed with this knowledge, we focused on the therapeutic potential of PGRN by isolating the domains of PGRN that interact with TNFRs, which led to the development of an engineered protein called “antagonist of TNF–TNFR signaling via targeting to TNF receptors,” or Atsttrin.

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

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

The discovery of PGRN as a crucial mediator of protein disaggregation may help to elucidate the currently puzzling relationship between PGRN deficiency and various neurodegenerative diseases. Consequently, our third research focus is determining the role and mechanism of PGRN in lysosomal storage diseases, Gaucher disease in particular, and associated neurodegenerative disorders.

Interferons are cytokines with multiple biological activities whose actions are realized via numerous interferon-inducible molecules. Our studies of interferon-inducible p200 family proteins revealed that they are important regulators of cellular proliferation and differentiation, as well as interferon activity. Deregulation of these proteins is linked to various diseases, including autoimmune and inflammation- and tumor-related conditions.

Our studies have focused on p204, a highly conserved murine ortholog of human interferon-inducible protein 16 (IFI16). Recently, p204/IFI16 was isolated as a cytoplasmic DNA sensor that induces the transcription of genes involved in the innate immune response, including TNFα/β. In addition, p204/IFI16 has the capacity to form an inflammasome within the cell nucleus and act as a sensor of nuclear pathogenic DNA. Our fourth research goal, therefore, 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.

Phone

212-598-6103

Academic office

301 East 17th Street

Sixteenth Floor

New York, NY 10003

Lab Website
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These focus areas and their associated publications are derived from medical subject headings from PubMed.
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Professor, Department of Orthopaedic Surgery

Professor, Department of Cell Biology

PhD from Shanghai Institute of Cell Biology

Lata, Michal; Hettinghouse, Aubryanna S; Liu, Chuan-Ju

Annals of the New York Academy of Sciences. 2019 Apr; 1442(1):5-16

Cui, Yazhou; Hettinghouse, Aubryanna; Liu, Chuan-Ju

Cytokine & growth factor reviews. 2019 Feb; 45:53-64

Chen, Yuehong; Liu, Ronghan; Hettinghouse, Aubryanna; Wang, Shuya; Liu, Gang; Liu, Chuan-Ju

JBJS reviews. 2019 Jan; 7(1):e10

Chen, Yuehong; Jian, Jinlong; Hettinghouse, Aubryanna; Zhao, Xueheng; Setchell, Kenneth D R; Sun, Ying; Liu, Chuan-Ju

Journal of molecular medicine (Berlin). 2018 Dec; 96(12):1359-1373

Osteocytic Kindlin-2 regulates bone mass accrual and maintenance and mediates skeletal response to mechanical loading and PTH anabolism [Meeting Abstract]

Cao, Huiling; Yan, Qinnan; Wang, Dong; Lai, Yumei; Lin, Simin; Lei, Yimin; Ma, Liting; Guo, Yuxi; Wang, Yishu; Wang, Yilin; Gao, Huanqing; Bai, Xiaochun; Liu, Chuanju; Feng, Jian Q.; Wu, Chuanyue; Chen, Di; Xiao, Guozhi

Journal of bone & mineral research. 2018 NOV; 33:31-31

Novel TNFR2 Signaling in Osteoarthritis [Meeting Abstract]

Fu, Wenyu; Yi, Young-Su; Mundra, Jyoti Joshi; Hettinghouse, Aubryanna; Liu, Chuanju

Journal of bone & mineral research. 2018 NOV; 33:220-220

Wei, Jian-Lu; Fu, Wenyu; Hettinghouse, Aubryanna; He, Wen-Jun; Lipson, Kenneth E; Liu, Chuan-Ju

Arthritis & rheumatology. 2018 Nov; 70(11):1745-1756