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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-like molecule 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 its 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 involved 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 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.

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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Zhu, Xiaofang; Li, Xiangfen; Wang, Xiaoxuan; Chen, Ting; Tao, Fengjuan; Liu, Chuanju; Tu, Qisheng; Shen, Guofang; Chen, Jake J

Journal of cellular physiology. 2020 Jun 22;

Zhu, Ke; Lai, Yumei; Cao, Huiling; Bai, Xiaochun; Liu, Chuanju; Yan, Qinnan; Ma, Liting; Chen, Di; Kanaporis, Giedrius; Wang, Junqi; Li, Luyuan; Cheng, Tao; Wang, Yong; Wu, Chuanyue; Xiao, Guozhi

Nature communications. 2020 Jan 24; 11(1):484

Pu, Xiangyuan; Chan, Kenneth; Yang, Wei; Xiao, Qingzhong; Zhang, Li; Moore, Andrew D; Liu, Chuanju; Webb, Tom R; Caulfield, Mark J; Samani, Nilesh J; Zhu, Jianhua; Ye, Shu

Atherosclerosis. 2020 Jan 21; 296:11-17

Wei, Jianlu; Zhang, Lei; Ding, Yuanjing; Liu, Ronghan; Guo, Yuqi; Hettinghouse, Aubryanna; Buza, John; De La Croix, Jean; Li, Xin; Einhorn, Thomas A; Liu, Chuan-Ju

Annals of the New York Academy of Sciences. 2020 Jan; 1460(1):43-56

Kuang, Liang; Wu, Jiangyi; Su, Nan; Qi, Huabing; Chen, Hangang; Zhou, Siru; Xiong, Yan; Du, Xiaolan; Tan, Qiaoyan; Yang, Jing; Jin, Min; Luo, Fengtao; Ouyang, Junjie; Zhang, Bin; Wang, Zuqiang; Jiang, Wanling; Chen, Liang; Chen, Shuai; Wang, Ziming; Liu, Peng; Yin, Liangjun; Guo, Fengjin; Deng, Chuxia; Chen, Di; Liu, Chuanju; Xie, Yangli; Ni, Zhenhong; Chen, Lin

Annals of the rheumatic diseases. 2020 Jan; 79(1):112-122

Cao, Huiling; Yan, Qinnan; Wang, Dong; Lai, Yumei; Zhou, Bo; Zhang, Qi; Jin, Wenfei; Lin, Simin; Lei, Yiming; Ma, Liting; Guo, Yuxi; Wang, Yishu; Wang, Yilin; Bai, Xiaochun; Liu, Chuanju; Feng, Jian Q; Wu, Chuanyue; Chen, Di; Cao, Xu; Xiao, Guozhi

Bone research. 2020; 8:2

Wang, Chao; Zhang, Lu; Ndong, Jean De La Croix; Hettinghouse, Aubryanna; Sun, Guodong; Chen, Changhong; Zhang, Chen; Liu, Ronghan; Liu, Chuan-Ju

Journal of neuroinflammation. 2019 Nov 27; 16(1):238

Wang, Yishu; Yan, Qinnan; Zhao, Yiran; Liu, Xin; Lin, Simin; Zhang, Peijun; Ma, Liting; Lai, Yumei; Bai, Xiaochun; Liu, Chuanju; Wu, Chuanyue; Feng, Jian Q; Chen, Di; Cao, Huiling; Xiao, Guozhi

JCI insight. 2019 11 14; 4(22):