Overview

Principal Investigator

Robert A. Colbert, M.D., Ph.D.

Robert Colbert, M.D., Ph.D., leads a team of scientists in the Pediatric Translational Research Branch studying the etiology and pathogenesis of early onset arthritis, including axial disease in juvenile spondyloarthritis.

The long-term goals of the Pediatric Translational Research laboratory are to understand cellular and molecular mechanisms underlying the pathogenesis of spondyloarthritis. Spondyloarthritis refers to a spectrum of chronic immune-mediated inflammatory diseases that affect an estimated 1% of the population. They differ from other types of inflammatory arthritis in genetic predisposition, pathogenesis, and long-term outcome. Spondyloarthritis often begins as an undifferentiated disease that, in many cases, progresses to ankylosing spondylitis (AS). AS can lead to ankylosis of the spine and significant disability. Although most people affected by AS are adults, approximately 15-20% are first affected as children. This juvenile onset AS (JAS) differs from adult onset disease because spinal (axial) symptoms are usually missing, while peripheral arthritis and enthesitis are more prominent. Most spondyloarthritis in children is classified as a form of juvenile idiopathic arthritis known as enthesitis-related arthritis (ERA) or psoriatic arthritis (PsA). However, children with ERA or PsA and spinal involvement are not distinguished from those with only peripheral arthritis and enthesitis. Since individuals with axial involvement are most likely to progress to AS, recognizing early spinal involvement in children is paramount.

The development of AS is primarily determined by one’s genetic make-up. HLA-B (predominantly the B27 allele) plays a major role, accounting for an estimated 30-40% of overall susceptibility, with additional genes, such as ERAP1, IL23R, IL1RII, IL1 (probably IL1A), CARD9, TNFR1, TRADD, STAT3, PTGER2, ANTXR2 and others also contributing. Our knowledge of how these genes and their variants work together to promote the inflammation and bone formation that occurs in AS is incomplete, although new targets have been identified. As therapeutic options improve, identification of children with spondyloarthritis who have axial involvement will be increasingly important, as they may benefit the most from early aggressive intervention.

Current projects include:

  • Evaluating the role of HLA-B27 and other genetic factors in disease.
    • Studies employ a transgenic animal model of spondyloarthritis and cells from human subjects including induced pluripotent stem cells (iPSC), to evaluate effects of HLA-B27 expression and misfolding on ER stress and its consequences for cytokine production and cellular function.
    • Effects on osteoclast and osteoblast development and function.
  • Elucidating genes that influence how HLA-B27 causes spondyloarthritis in rats.
  • Determining how ERAP1 affects spondyloarthritis pathogenesis.
  • Understanding how HLA-B27 shapes the immunology and microbiology of the gut.
  • Determining clinical manifestations and biomarkers of early axial spondyloarthritis in children.

These studies will inform us on mechanisms that drive pathogenesis of spondyloarthritis and suggest novel strategies that can be developed to more effectively treat disease.

Staff

Deputy Clinical Director
Chief
301-443-8935
Assistant Clinical Investigator
301-443-7961
Research Fellow
301-827-2892
Research Coordinator; Study Nurse
301-451-6761
Postdoctoral Fellow (IRTA)
301-451-1187
Lawrence Shulman Scholar
Clinical Fellow
301-594-6196
Staff Scientist
301-451-6019
Postbaccalaureate Fellow
301-451-4362
Biologist
Research Assistant
301-402-3838
Research Fellow
301-451-1207
Postbaccalaureate Fellow
301-451-4362
Special Volunteer
414-520-0811
Special Volunteer
Clinical Fellow
301-402-1376
Research Fellow
301-827-0958

Image & Media Gallery

Scientific Publications

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 Aug;65(8):2123-31. doi: 10.1002/art.38001.

Colbert RA, Tran TM, Layh-Schmitt G. HLA-B27 misfolding and ankylosing spondylitis. Mol Immunol. 2013 Aug 29. pii: S0161-5890(13)00479-3. doi: 10.1016/j.molimm.2013.07.013. [Epub ahead of print]

Stojanov S, Lapidus S, Chitkara P, Feder H, Salazar JC, Fleisher TA, Brown MR, Edwards KM, Ward MM, Colbert RA, Sun HW, Wood GM, Barham BK, Jones A, Aksentijevich I, Goldbach-Mansky R, Athreya B, Barron KS, Kastner DL. Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) is a disorder of innate immunity and Th1 activation responsive to IL-1 blockade. Proc Natl Acad Sci U S A. 2011 Apr 8

Latest News

no-news-results
Last Reviewed: 02/17/2017