An official website of the United States government
          Here’s how you know
        Here’s how you know**Official websites use .gov**A
              **.gov** website belongs to an official government
              organization in the United States.
        **Secure .gov websites use HTTPS**A
              **lock** (
              Locked padlock icon) or **https://** means you’ve safely connected to the .gov website. Share sensitive information only on official, secure websites.
 Top Utility Nav
        
        
        Asian-Language Resources
        
        Portal en español


Site search Mega Menu
  

        

        Home
                  Health Topics
                                      
    
  Health Topics

    Arthritis and Rheumatic Diseases
          
    Muscle and Bone Diseases
          
    Skin Diseases
          
    All Diseases and Conditions
          
    Publication Catalog
                  Grants & Funding
                                      
    
  Grants & Funding

    Current Funding Opportunities
          
    Supported Scientific Programs
          
    NIAMS-Supported Programs
          
    Applying for a Grant
          
    NIH Policies and Guidance
          
    Peer Review and Grants Administration Resources
          
    Types of Funding Mechanisms (Activity Codes)
                  Labs @ NIAMS
                                      
    
  Labs @ NIAMS

    NIAMS Labs and Core Facilities
          
    Research Faculty
          
    Research Areas
          
    NIAMS Scientific Advances
          
    Training and Career Development
                  Clinical Trials
                                      
    
  Clinical Trials
      
            For Principal Investigators

    Clinical Trial Policies, Guidelines, and Templates
          
    Conducting Clinical Trials
          
    Register with ClinicalTrials.gov

For Patients

What is a Clinical Trial?
	Clinical Trials at NIAMS
	Clinical Trials in the Spotlight
                  News & Events
                                      
    
  Newsroom

    All NIAMS News
          
    NIAMS Newsletters
          
    Meetings & Events
                  About NIAMS
                                      
    
  About NIAMS

    Director's Page
          
    NIAMS Organization
          
    Strategic Plan Fiscal Years 2020-2024
          
    Staff Directory
          
    NIAMS Budget
          
    Partnerships
          
    Contact NIAMS
                  Community Outreach
                                      
    
  Community Outreach

    Bone Health
          
    Joint Health
          
    Muscle, Tendon, and Ligament Health
          
    Skin Health
          
    Health Information For Kids And Young Adults
          
    Health Information For Older Adults/Seniors
          
    Printable Materials for Community Events
          
    Resources in Other Languages
          
    Annual Health Observances
          
    Social Media Resources Breadcrumb
    Home
          Labs @ NIAMS
          Pediatric Translational Research Branch








Pediatric Translational Research Branch


Robert A. Colbert, M.D., Ph.D. FacebookEmailPrintFacebookEmail
        Image
              Computer image showing ankylosing spondylosis and bone formation.

      Overview

                                  Senior Investigator
      
  


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


            Clinical Director
      
            colbertr@mail.nih.gov
      
                                                                        

  
   Research Areas (IRP Lab Groups)
          Cell Biology,
          Clinical Research,
          Genetics and Genomics,
          Immunology,
          Molecular Biology and Biochemistry,
          Stem Cell Biology
                                
            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.
      

                                            Scientific Advances
      
  

      February 1, 2023Loss of an Enzyme in the Endoplasmic Reticulum—a Cell’s Transportation System—Might Play a Protective Role in Spondyloarthritis

                                                      Core Research Facilities

Labs at the NIAMS are supported by the following state-of-the-art facilities and services:

Biodata Mining and Discovery
	Flow Cytometry
	Genomic Technology
	Laboratory Animal Care and Use
	Light Imaging
	Translational Immunology

                                    Staff
                            
            **Robert A. Colbert, M.D., Ph.D.**Clinical DirectorSenior Investigatorcolbertr@mail.nih.gov
    **Yongquan Luo, Ph.D.**Biologistluoyo@mail.nih.gov
    **Fatemeh (Elham) Navid, Ph.D.**Staff Scientistnavidf2@mail.nih.gov
    **Pankaj Sharma, Ph.D.**Research Fellowpankaj.sharma2@nih.gov
    **Hema Srinivasalu, M.D.**Special Volunteersrinivasaluh@mail.nih.gov
            
                                                Image & Media Gallery
              
            Rat macrophage expressing HLA-B27
Rat macrophage expressing HLA-B27
        ×
      Rat macrophage expressing HLA-B27
        Rat macrophage expressing HLA-B27. Correctly folded HLA-B27 (green) is assembled in the endoplasmic reticulum (ER) and transported through the golgi to the cell surface. Misfolded HLA-B27 (red) is accumulating in the ER causing an ER stress. Image taken by Fatemeh Navid.
    Differentiation of induced pluripotent stem cells (iPSCs) into stromal cells and hematopoietic precursors.
Differentiation of induced pluripotent stem cells (iPSCs) into stromal cells and hematopoietic precursors.
        ×
      Differentiation of induced pluripotent stem cells (iPSCs) into stromal cells and hematopoietic precursors.
        Differentiation of induced pluripotent stem cells (iPSCs) into stromal cells and hematopoietic precursors. iPSCs used as a valuable source for generating osteoblasts, chondrocytes and osteoclast for analyzing pathways relevant to ankylosing spondylitis. Images taken by Gerlinde Layh-Schmitt. *Clin Rheumatol*. 2017; 36(1): 143–15
    Robert Colbert, M.D., Ph.D., Amy Petrik, Ph.D., and Grace Kwon, Ph.D. Examine Skin Fibroblasts under a Microscope.
Robert Colbert, M.D., Ph.D., Amy Petrik, Ph.D., and Grace Kwon, Ph.D. Examine Skin Fibroblasts under a Microscope.
        ×
      Robert Colbert M.D. Ph.D. Amy Petrik Ph.D. and Grace Kwon Ph.D. Examine Skin Fibroblasts under a Microscope.
        Robert Colbert, M.D., Ph.D., Chief, NIAMS Pediatric Translational Research Branch (PTRB). Dr. Robert Colbert trains Dr. Amy Petrik (Post-Doctoral Student) and Dr. Grace Kwon (Post-Doctoral Student) in the lab. They are examining skin fibroblasts under a microscope. Skin fibroblasts are reprogrammed into induced pluripotent stem cells (iPSC), which can then be differentiated into bone forming cells. These are used to study how specific genetic variants associated with susceptibility to ankylosing spondylitis, help cause spinal ankylosis. The PTRB researches spondyloarthritis and related disorders—including ankylosing spondylitis—particularly with childhood onset. Dr. Robert Colbert is developing a research program to characterize the mechanisms responsible for initiating and promoting inflammation and dysregulated bone formation in these disorders. These studies will build on recent advances in our understanding of the genetics of ankylosing spondylitis, including the role of the immune system in mediating inflammation.
    HLA-B27 Model
HLA-B27 Model
        ×
      Proposed model linking HLA-B27 misfolding and the unfolded protein response (UPR) to IL-23 production and Th17 activation.
        Proposed model linking HLA-B27 misfolding and the unfolded protein response (UPR) to IL-23 production and Th17 activation.
            
                        
                                    Clinical Trials
              
              
            RecruitingNatural History and Development of SpondyloarthritisClinicalTrials.gov Identifier: NCT01422694Spondyloarthritis encompasses a spectrum of immune-mediated inflammatory diseases that exhibit overlapping features, but differ from other types of inflammatory arthritis in genetic predisposition, pathogenesis, and outcome. Ankylosing spondylitis (AS). Researchers are interested in studying people with SpA and their relatives to determine which people are more likely to develop more severe conditions.
    Active, not recruitingStopping Tumor Necrosis Factor-Alpha Inhibitors in Rheumatoid Arthritis (STARA)ClinicalTrials.gov Identifier: NCT01793519Researchers want to see if people with RA in remission on a TNF inhibitor can stay in remission without this medicine. Also there may be a clinical, imaging (MRI, ultrasound), laboratory profile that will help to determine which patients remain in remission after stopping these drugs. This study will provide important new information on the best treatment approach for patients with RA in remission.
            
                                    Scientific Publications
              Selected Recent Publications
                  
      Reliability assessment of the OMERACT whole-body magnetic resonance imaging scoring system for juvenile idiopathic arthritis.

    Panwar J, Tolend M, Kirkhus E, Meyers AB, Redd B, Sudol-Szopinska I, Varma N, Inarejos Clemente EJ, Colbert RA, Akikusa J, Appenzeller S, Carrino JA, Herregods N, Highmore K, Jans L, Jaremko JL, von Kalle T, van Rossum MA, Rumsey DG, Srinivasalu H, Stimec J, Tse SM, Twilt M, Tzaribachev N, Doria AS
        

                    Semin Arthritis Rheum.
        
                    2024 Mar 16;
        
                    66().
        
                    doi: 10.1016/j.semarthrit.2024.152437
                            PMID: 38564998
              VEGF Secretion Drives Bone Formation in Classical MAP2K1+ Melorheostosis.

    Allbritton-King JD, Maity J, Patel A, Colbert RA, Navid F, Bhattacharyya T
        

                    J Bone Miner Res.
        
                    2023 Dec;
        
                    38(12).
        
                    doi: 10.1002/jbmr.4915
                            PMID: 37737377
              Paradoxical Effects of Endoplasmic Reticulum Aminopeptidase 1 Deficiency on HLA-B27 and Its Role as an Epistatic Modifier in Experimental Spondyloarthritis.

    Tran TM, Gill T, Bennett J, Hong S, Holt V, Lindstedt AJ, Bakshi S, Sikora K, Taurog JD, Breban M, Navid F, Colbert RA
        

                    Arthritis Rheumatol.
        
                    2023 Feb;
        
                    75(2).
        
                    doi: 10.1002/art.42327
                            PMID: 36577442
              Recent Updates in Juvenile Spondyloarthritis.

    Srinivasalu H, Sikora KA, Colbert RA
        

                    Rheum Dis Clin North Am.
        
                    2021 Nov;
        
                    47(4).
        
                    doi: 10.1016/j.rdc.2021.07.001
                            PMID: 34635292
              Consensus-driven conceptual development of a standardized whole body-MRI scoring system for assessment of disease activity in juvenile idiopathic arthritis: MRI in JIA OMERACT working group.

    Panwar J, Tolend M, Redd B, Srinivasalu H, Colbert RA, Akikusa J, Appenzeller S, Carrino JA, Herregods N, Jans L, Highmore K, von Kalle T, Kirkhus E, Rumsey DG, Jaremko JL, Clemente IEJ, van Rossum MA, Stimec J, Tse SM, Twilt M, Tzaribachev N, Sudol-Szopinska I, Meyers AB, Doria AS
        

                    Semin Arthritis Rheum.
        
                    2021 Dec;
        
                    51(6).
        
                    doi: 10.1016/j.semarthrit.2021.07.017
                            PMID: 34465447
              JAK1: Number one in the family; number one in inflammation?

    Spinelli FR, Colbert RA, Gadina M
        

                    Rheumatology (Oxford).
        
                    2021 May 5;
        
                    60(Suppl 2).
        
                    doi: 10.1093/rheumatology/keab024
                            PMID: 33950229
              Janus kinase (JAK) inhibition with baricitinib in refractory juvenile dermatomyositis.

    Kim H, Dill S, O'Brien M, Vian L, Li X, Manukyan M, Jain M, Adeojo LW, George J, Perez M, Grom AA, Sutter M, Feldman BM, Yao L, Millwood M, Brundidge A, Pichard DC, Cowen EW, Shi Y, Lu S, Tsai WL, Gadina M, Rider LG, Colbert RA
        

                    Ann Rheum Dis.
        
                    2021 Mar;
        
                    80(3).
        
                    doi: 10.1136/annrheumdis-2020-218690
                            PMID: 32843325
              HLA-B27 misfolding and ankylosing spondylitis.

    Colbert RA, Tran TM, Layh-Schmitt G
        

                    Mol Immunol.
        
                    2014 Jan;
        
                    57(1).
        
                    doi: 10.1016/j.molimm.2013.07.013
                            PMID: 23993278
              HLA-B27 alters the response to tumor necrosis factor α and promotes osteoclastogenesis in bone marrow monocytes from HLA-B27-transgenic rats.

    Layh-Schmitt G, Yang EY, Kwon G, Colbert RA
        

                    Arthritis Rheum.
        
                    2013 Aug;
        
                    65(8).
        
                    doi: 10.1002/art.38001
                            PMID: 23666508
              Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) is a disorder of innate immunity and Th1 activation responsive to IL-1 blockade.

    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
        

                    Proc Natl Acad Sci U S A.
        
                    2011 Apr 26;
        
                    108(17).
        
                    doi: 10.1073/pnas.1103681108
                            PMID: 21478439
            
                                    News & Highlights
              
            no-news-results



    FacebookEmailPrintFacebookEmail
        Last Updated: April 2024
 About NIAMS
                    Clinical Trials
                    Grants & Funding
                    Health Topics
                    Labs @ NIAMS
              News Room
                    NIAMS Multimedia Library
                    Disclaimer
                    FOIA
                    Contact us
              Privacy Statement
                    Accessibility
                    HHS Vulnerability Disclosure
                    Social Media Moderation Policy
                    NIAMS Archives
        Subscribe to Our E-Newsletters
            Click the button to see different options to sign up for newsletters.
            Click Here to Subscribe
          Follow us on
  
  About NIH
                  Accessibility Support
            FOIA requests
                  No FEAR Act data
            Office of the Inspector General
                  Performance reports
            Privacy Policy Back to Top