Degradative COMP Fragments as a Biomarker of Arthritis

降解性 COMP 片段作为关节炎的生物标志物

基本信息

批准号：
7884343
负责人：
Chuanju Liu
金额：
$ 12.75万
依托单位：
NEW YORK UNIVERSITY SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-08-01 至 2012-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7884343
关键词：
ADAMTS Address Affect Age Amino Acid Sequence Arthritis Baculoviruses Binding Biochemical Biological Assay Biological Markers Biological Markers Biology Blocking Antibodies Blood Body Fluids C-terminal Cartilage Catalytic Domain Chondrocytes Clinical Clinical Research Data Databases Degenerative polyarthritis Detection Diagnosis Digestion Disease Disintegrins Early Diagnosis Elderly Enzyme-Linked Immunosorbent Assay Enzymes Etiology Extracellular Matrix Proteins Foundations Goals Harvest Healthcare Human Hyperostosis Immunohistochemistry In Situ Hybridization In Vitro Inflammation Institution Interleukin-1 beta Investigation Joint Capsule Joints Knowledge Mentors Messenger RNA Metalloproteases Monitor Monoclonal Antibodies Musculoskeletal Diseases Musculoskeletal System N-terminal Northern Blotting PC cell-derived growth factor Pain Pathogenesis Patients Pattern Peptide Sequence Determination Physiological Population Prevalence Process Protein Binding Domain Protein Fragment Proteins Proteolysis Public Health Quality of life Recombinants Research Research Proposals Sampling Scientist Sclerosis Serum Services Site Societies Staging Structure Symptoms Synovial Fluid Synovial Membrane Testing Tissue Banking Tissue Banks Tumor Necrosis Factor-alpha Ulcer Urine Western Blotting Zinc articular cartilage base career career development cartilage metabolism design disability experience granulin improved inhibitor/antagonist mammalian COMP mutant novel outcome forecast programs protein degradation repaired research study skills treatment effect

项目摘要

DESCRIPTION (provided by the applicant): 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.

DESCRIPTION (provided by the applicant): 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负责关节炎的内源性降解。为了检验这些假设，申请人将进行实验，以（1）确定Comp片段作为关节炎的生物标志物的特定目的；（2）表征负责关节炎中补充降解的酶和相关的内源性抑制剂；（3）确定要开发的COMP片段ELISA是否比目前可用的ELISA更敏感和特异性ELISA在检测患有和没有关节炎患者血清的软骨变性方面。申请人已经将自己作为一名富有成效的科学家。他的近期目标是提高他的知识和研究技能，因为它们适用于肌肉骨骼系统，他的长期目标是扩展他的基本科学研究，以推进肌肉骨骼疾病的诊断和治疗。该提案旨在为他提供临床研究设计和管理方面的新知识和经验，从而使他能够从事独立的临床研究科学家职业。申请人将在著名的临床医生 - 科学家史蒂芬·艾布拉姆森（Steven Abramson）博士的指导下，通过一项结构化的职业发展计划来开发必要的专业知识。与公共卫生有关：关节炎最终使大多数人都折磨，但无法治愈。关节炎的生物学标志物的发现有望使我们的治疗关节炎的能力显着改善，尤其是在早期诊断和治疗方面的治疗能力，在明显的关节软骨丧失之前已经开始。