Robert Colbert, M.D., Ph.D.
Pediatric Translational Research Branch
Building 10-CRC, Room 1-5142
10 Center Drive
Bethesda, MD 20814
The mission of the Pediatric Translational Research Branch (PTRB) is to understand the pathogenesis of chronic inflammation and its impact on structural remodeling of bone in spondyloarthritic diseases such as ankylosing spondylitis. Recent advances from genome wide association studies are beginning to bring genetic susceptibility into focus and suggest that a relatively small number of genes may account for the majority of risk. Fitting the pieces of the complex genetic puzzle together into a cogent pathogenic mechanism for this and other rheumatic diseases remains one of the great challenges in medicine.
While some of the susceptibility genes are envisioned to create a pro-inflammatory diathesis, others are implicated in downstream pathways and may affect responsiveness of cells and tissues to inflammatory mediators and contribute to the unique phenotype. One strategy of the PTRB is to make use of animal models that facilitate molecular dissection of gene function in spondyloarthritis, including the influence of polymorphisms, combined with translational approaches using patient derived material to establish relevance. Recent studies have focused on the role of HLA-B27 in rat spondyloarthritis, resulting in the discovery that this gene product has a tendency to misfold, generating ER stress and activating the unfolded protein response (UPR) particularly when HLA-B27 is upregulated. Novel links between the UPR and inflammatory cytokine production that may drive Th17 activation have also been uncovered. Major projects include: (1) evaluating mechanism and consequences of HLA-B27 misfolding and the UPR on (a) IL-23 production and Th17 activation in rat spondyloarthritis; (b) osteoclast and osteoblast development and function; (2) elucidating genes that influence the development of HLA-B27-associated spondyloarthritis in rats; (3) determining how ERAP1/ARTS1, a newly discovered susceptibility gene, affects disease pathogenesis including functional interactions with HLA-B27 and/or effects on cytokine receptor biology; (4) understanding how susceptibility genes and gene products found to be differentially expressed in spondyloarthritis, modify downstream events in TNF-a-driven sacroiliitis including structural remodeling in post-inflammatory phases of disease. Through these studies we hope to determine how a genotype comprised of relatively common alleles results in a unique disease phenotype, with implications for new treatment strategies.
Before coming to NIAMS, Dr. Colbert served as the director of the Division of Rheumatology at Cincinnati Children's Hospital Medical Center (CCHMC) of the University of Cincinnati College of Medicine (UCCOM). He is certified in pediatric rheumatology by the American Board of Pediatrics and holds memberships in the American Academy of Pediatrics, the American Association of Immunologists, the American College of Rheumatology, the Society for Pediatric Research, and the American Pediatric Society. His research career has included authoring 53 papers and serving as an investigator on a number of NIAMS and other NIH and industry-funded research studies. Dr. Colbert’s accomplishments have been recognized in numerous honors and awards, including Pfizer Postdoctoral Fellowship and Scholar Awards, the James R. Klinenberg Science Award from the Arthritis Foundation, and the American College of Rheumatology’s Deborah Kredich Pediatric Rheumatology Service Award.
Lin P, Bach M, Asquith M, Lee AY, Akileswaran L, Stauffer P, Davin S, Pan Y, Cambronne ED, Dorris M, Debelius JW, Lauber CL, Ackermann G, Baeza YV, Gill T, Knight R, Colbert RA, Taurog JD, Van Gelder RN, Rosenbaum JT. HLA-B27 and human β2-microglobulin affect the gut microbiota of transgenic rats. PLoS One. 2014;9(8):e105684.
Tran TM, Hong S, Edwan JH, Colbert RA. ERAP1 reduces accumulation of aberrant and disulfide-linked forms of HLA-B27 on the cell surface. Mol Immunol. 2016;74:10-7.
DeLay ML, Turner MJ, Klenk EI, Smith JA, Sowders DP, Colbert RA. HLA-B27 misfolding and the unfolded protein response augment interleukin-23 production and are associated with Th17 activation in transgenic rats. Arthritis Rheum. 2009;60(9):2633-43.
Layh-Schmitt G, Yang EY, Kwon G, Colbert RA. HLA-B27 alters the response to tumor necrosis factor α and promotes osteoclastogenesis in bone marrow monocytes from HLA-B27-transgenic rats. Arthritis Rheum. 2013;65(8):2123-31.
Taurog JD, Chhabra A, Colbert RA. Ankylosing Spondylitis and Axial Spondyloarthritis. N Engl J Med. 2016;374(26):2563-74.
Related Scientific Focus Areas
Genetics and Genomics
This page was last updated on September 5th, 2017