BCCMA: Targeting Osteoarthritis Pain and Progression: Proteomics, RNASeq & Immunostaining to elucidate the immune pathotypes of OA

BCCMA:针对骨关节炎疼痛和进展:蛋白质组学、RNASeq

基本信息

项目摘要

The TOPP Collaborative Merit will test the central hypothesis that heterogeneity in OA pain and structural progression is related to the “immune pathotype” of OA, which arises from the variability in the cellular and molecular responses of bone, cartilage, and synovium to inflammation and joint mechanical environment. The overarching Specific Aims are: Aim 1: To improve understanding of osteoarthritis (OA) pathogenesis to enable development of targeted early treatment approaches; and Aim 2: To establish preclinical and clinical data for new therapeutic targets to reduce pain and prevent OA progression. This VA Merit is Project 2 of our TOPP Collaborative Merit. This Merit will use biospecimens from early and late OA clinical cohorts prevalent in the the VA health care system to define the immune pathotypes of OA, with the ultimate goal of using biomarkers for these pathotypes to guide care. Previous studies from our laboratory implicate “low-grade” innate immune inflammation, and we previously identified key roles for dysregulated activation of the complement system, mast cells, and inflammatory macrophage in the pathogenesis of OA. In further invetigations of the cellular, transcriptional and molecular profiles of synovial membranes from early and late OA, we observe distinct transcriptional signatures, immune cell populations, and immune pathway activation. We hypothesize that differences in the immune cell composition and activation states in synovium, bone and cartilage will identify “immune pathotypes” of OA, and that these immune pathotypes will be associated with differential levels of pain, structural progression, and/or response to treatment. In Aim 1, we propose to perform proteomic, bulk RNA-Seq, single cell RNA-Seq, and multiplex immunostaining of human pre-OA (with Dr. Chu) and OA synovial tissues. Aim 2 will perform integrated informatic analyses using machine learning and other approaches to identify immune pathotypes of human pre-OA and OA. Aim 3 will determine if the immune pathotypes identified correlate with OA pain and structural pathology in humans, and/or response to tVNS (with Dr. Humphrey) or anti-NGF (with Dr. Nakamura) in mice. Success of the herein proposed studies and of our overarching TOPP Collaborative Merit proposal would transform our understanding of the pathobiology of OA, and could lead to more effective approaches to treat pain and the first ever disease-modifying therapy for OA.
TOPP协作优点将检验OA疼痛和结构性疼痛异质性的中心假设

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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William H Robinson其他文献

Immune tolerance of citrullinated peptides.
瓜氨酸肽的免疫耐受。
  • DOI:
    10.1038/s41584-024-01081-0
  • 发表时间:
    2024
  • 期刊:
  • 影响因子:
    0
  • 作者:
    R. Thomas;William H Robinson
  • 通讯作者:
    William H Robinson
Imatinib for the treatment of rheumatic diseases
伊马替尼用于治疗风湿性疾病
  • DOI:
    10.1038/ncprheum0465
  • 发表时间:
    2007-04-01
  • 期刊:
  • 影响因子:
    32.700
  • 作者:
    Ricardo T Paniagua;William H Robinson
  • 通讯作者:
    William H Robinson
Human peptidome display
人类肽组展示
  • DOI:
    10.1038/nbt.1888
  • 发表时间:
    2011-06-07
  • 期刊:
  • 影响因子:
    41.700
  • 作者:
    William H Robinson;Lawrence Steinman
  • 通讯作者:
    Lawrence Steinman

William H Robinson的其他文献

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{{ truncateString('William H Robinson', 18)}}的其他基金

Investigating the IL-4/13 Axis in Osteoarthritis
研究骨关节炎中的 IL-4/13 轴
  • 批准号:
    9891690
  • 财政年份:
    2020
  • 资助金额:
    --
  • 项目类别:
Investigating the IL-4/13 Axis in Osteoarthritis
研究骨关节炎中的 IL-4/13 轴
  • 批准号:
    10092814
  • 财政年份:
    2020
  • 资助金额:
    --
  • 项目类别:
Investigating the IL-4/13 Axis in Osteoarthritis
研究骨关节炎中的 IL-4/13 轴
  • 批准号:
    10438519
  • 财政年份:
    2020
  • 资助金额:
    --
  • 项目类别:
Investigating the IL-4/13 Axis in Osteoarthritis
研究骨关节炎中的 IL-4/13 轴
  • 批准号:
    10553629
  • 财政年份:
    2020
  • 资助金额:
    --
  • 项目类别:
ShEEP Request for BioPlex 3D System
ShEEP 请求 BioPlex 3D 系统
  • 批准号:
    9796566
  • 财政年份:
    2019
  • 资助金额:
    --
  • 项目类别:
Targeting Mast Cells in Post-Traumatic Joint Rehabilitation and Osteoarthritis
在创伤后关节康复和骨关节炎中靶向肥大细胞
  • 批准号:
    10025268
  • 财政年份:
    2018
  • 资助金额:
    --
  • 项目类别:
Targeting Mast Cells in Post-Traumatic Joint Rehabilitation and Osteoarthritis
在创伤后关节康复和骨关节炎中靶向肥大细胞
  • 批准号:
    10672163
  • 财政年份:
    2018
  • 资助金额:
    --
  • 项目类别:
Targeting Mast Cells in Post-Traumatic Joint Rehabilitation and Osteoarthritis
在创伤后关节康复和骨关节炎中靶向肥大细胞
  • 批准号:
    10284924
  • 财政年份:
    2018
  • 资助金额:
    --
  • 项目类别:
Large-Scale Characterization of Anti-Cancer Antibody Responses in Lung Adenocarci
肺腺癌抗癌抗体反应的大规模表征
  • 批准号:
    8664101
  • 财政年份:
    2014
  • 资助金额:
    --
  • 项目类别:
Large-Scale Sequencing and Characterizing of Autoantibody Responses
自身抗体反应的大规模测序和表征
  • 批准号:
    8732967
  • 财政年份:
    2014
  • 资助金额:
    --
  • 项目类别:

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