Joint damage and synovial inflammation in rheumatoid arthritis (RA) are influenced by genetic and environmental factors. In our previous studies, we have identified a panel of genes and pathways that could be targeted for RA by integrating DNA methylation data with transcriptomics and RA risk gene data. Built upon these results, we will construct a gene network composed of RA relevant genes whose expression profiles represent RA pathogenesis. We will develop a novel systems biology method to search for synergistic therapeutic targets in this gene network. Once completed, this proposed work will not only identify drug targets for effective treatment of RA but also shed light into understanding the regulatory mechanisms of disease formation.

Public Health Relevance

Fibroblast-like synoviocytes (FLS) play a major role in joint inflammation and destruction in rheumatoid arthritis (RA). We have performed integrative analysis of omics data to identify genes relevant to RA. This proposal will develop a systems biology approach to search for synergistic therapeutic targets for effective treatment of RA.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AR070310-01
Application #
9164023
Study Section
Special Emphasis Panel (ZRG1-MOSS-C (02)S)
Program Officer
Mao, Su-Yau
Project Start
2016-09-15
Project End
2018-06-30
Budget Start
2016-09-15
Budget End
2017-06-30
Support Year
1
Fiscal Year
2016
Total Cost
$204,600
Indirect Cost
$72,600
Name
University of California San Diego
Department
Type
Schools of Arts and Sciences
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Yu, Bingfei; Zhang, Kai; Milner, J Justin et al. (2017) Epigenetic landscapes reveal transcription factors that regulate CD8+ T cell differentiation. Nat Immunol 18:573-582