: The central hypotheses of this proposal's Research Plan are that detection of cartilage oligomeric matrix protein (COMP) degradative fragments will yield a sensitive and specific marker of arthritis and that the zinc metalloproteinase ADAMTS-7 (ADAMTS = a disintegrin and metalloproteinase with thrombospondin motifs) will be the first physiological enzyme found to be responsible for endogenous COMP degradation in arthritis. To test these hypotheses, the applicant will conduct experiments with the specific aims of (1) determining the potential of COMP fragments as a biomarker of arthritis; (2) characterizing the enzyme(s) and associated endogenous inhibitors responsible for COMP degradation in arthritis; and (3) determining whether the COMP fragment ELISA to be developed is more sensitive and specific than the currently available ELISA in detecting cartilage degeneration in serum from patients with and without arthritis. The applicant has already distinguished himself as a productive scientist. His immediate goal is to improve his knowledge and research skills as they apply to the musculoskeletal system, and his long-term goal is to extend his basic scientific investigations in the service of advancing the diagnosis and treatment of musculoskeletal disorders. The proposal is designed to provide him with new knowledge and experience in the design and management of clinical research studies, allowing him to launch a career as an independent clinical research scientist. The applicant will develop the necessary expertise through a structured career development program under the guidance of mentor Dr. Steven Abramson, a prominent clinician-scientist. Relevance to Public Health: Arthritis eventually afflicts the majority of people, but there is no cure for it. The discovery of biological markers of arthritis promises to bring about dramatic improvement in our ability to treat arthritis, particularly with regard to early diagnosis and institution of treatment before marked loss of joint cartilage has begun. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01AR053210-02
Application #
7477791
Study Section
Special Emphasis Panel (ZAR1-CHW-M (M2))
Program Officer
Tyree, Bernadette
Project Start
2007-08-01
Project End
2012-07-31
Budget Start
2008-08-01
Budget End
2009-07-31
Support Year
2
Fiscal Year
2008
Total Cost
$127,548
Indirect Cost
Name
New York University
Department
Orthopedics
Type
Schools of Medicine
DUNS #
121911077
City
New York
State
NY
Country
United States
Zip Code
10016
Wei, Jian-Lu; Buza 3rd, John; Liu, Chuan-Ju (2016) Does progranulin account for the opposite effects of etanercept and infliximab/adalimumab in osteoarthritis?: Comment on Olson et al.: ""Therapeutic Opportunities to Prevent Post-Traumatic Arthritis: Lessons From the Natural History of Arthritis After Art J Orthop Res 34:12-4
Lai, Yongjie; Bai, Xiaohui; Zhao, Yunpeng et al. (2014) ADAMTS-7 forms a positive feedback loop with TNF-? in the pathogenesis of osteoarthritis. Ann Rheum Dis 73:1575-84
Zhao, Yunpeng; Liu, Ben; Liu, Chuan-ju (2014) Establishment of a surgically-induced model in mice to investigate the protective role of progranulin in osteoarthritis. J Vis Exp :e50924
Zhao, Yun-Peng; Tian, Qing-Yun; Liu, Chuan-Ju (2013) Progranulin deficiency exaggerates, whereas progranulin-derived Atsttrin attenuates, severity of dermatitis in mice. FEBS Lett 587:1805-10
Zhao, Yun-peng; Tian, Qing-yun; Frenkel, Sally et al. (2013) The promotion of bone healing by progranulin, a downstream molecule of BMP-2, through interacting with TNF/TNFR signaling. Biomaterials 34:6412-21
Jian, Jinlong; Konopka, Jessica; Liu, Chuanju (2013) Insights into the role of progranulin in immunity, infection, and inflammation. J Leukoc Biol 93:199-208
Tian, Qing-Yun; Zhao, Yun-Peng; Liu, Chuan-ju (2012) Modified yeast-two-hybrid system to identify proteins interacting with the growth factor progranulin. J Vis Exp :
Liu, Chuan-ju; Bosch, Xavier (2012) Progranulin: a growth factor, a novel TNFR ligand and a drug target. Pharmacol Ther 133:124-32
Lai, Y; Yu, X-P; Zhang, Y et al. (2012) Enhanced COMP catabolism detected in serum of patients with arthritis and animal disease models through a novel capture ELISA. Osteoarthritis Cartilage 20:854-62
Liu, Chuan-ju (2011) Progranulin: a promising therapeutic target for rheumatoid arthritis. FEBS Lett 585:3675-80

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