Lupus Center

Robert A. Colbert, MD, PhD

Title

Director, Division of Rheumatology

Appointment

Professor of Pediatrics; Director, Division of Rheumatology; Associate Director, Physician Scientist (MD / PhD); Training Program, University of Cincinnati College of Medicine

Email

bob.colbert@cchmc.org

Phone

513-636-6320

Fax

513-636-4116

Credentials

PhD: University of Rochester, Rochester, NY, 1986.

MD: University of Rochester, Rochester, NY, 1987.

Residency: Pediatrics, Strong Memorial Hospital, Rochester, NY.

Fellowship: Pediatric Rheumatology, Duke University Medical Center, Durham, NC; North Carolina Memorial Hospital, Chapel Hill, NC.

Certification: Pediatrics, 1990; Pediatric Rheumatology, 1992.

Research

Visit Dr. Colbert's lab web site for more details about his research.

Major histocompatibility complex (MHC) class I proteins are critical recognition elements in the cellular immune system. During their assembly, they bind peptides produced by proteasome-mediated degradation of intracellular proteins, and are then displayed on the cell surface where they can be recognized by T lymphocytes. Certain MHC proteins confer susceptibility to arthritis, although the mechanisms underlying these processes are unknown.

My laboratory is studying how one closely related group of MHC class I molecules, referred to as HLA-B27, can cause a type of arthritis known as anklyosing spondylitis. They are investigating the folding and intracellular assembly of HLA-B27 to elucidate unique aspects of this molecule that may contribute to its arthritogenicity. Transgenic animal models are used to determine what unique structural and functional characteristics are relevant to the pathogenesis of arthritis.

The laboratory has also identified a cooperative assembly mechanism producing a specialized set of proteasomes called immunoproteasomes, that are important for the generation of self and antigenic peptides that bind to MHC class I molecules. Further studies aimed at defining the role of proteasome subunit prosequences in assembly are being carried out, and will be combined with attempts to define and evaluate subpopulations of proteasomes for functional differences.

The role of HLA-B27 in the pathogenesis of spondyloarthritis. Immunological effects of protein misfolding, endoplasmic reticulum stress and activation of the unfolded protein response (UPR). Convergence of UPR and Toll-like receptor (TLR) signaling pathways.
Biomarkers of subtypes of juvenile arthritis; predicting outcome in early spondyloarthritis.

Research Grants and Contracts

NIH R01 (AR 48372) "HLA-B27 Misfolding in Spondyloarthropathy Pathogenesis"

NIH P01 (AR 48929) "Gene Expression in Pediatric Arthritis"

Publications, Most Recent

View Robert Colbert's publications at Cincinnati Children's as listed by PubMed.

Caudill, C.M.; Jayarapu, K.; Elenich, L.; Monaco, J.J.; Colbert, R.A.; Griffin, T.A.: T cells lacking immunoproteasomes subunits MECL-1 and LMP7 hyperproliferate in response to polyclonal mitogens.J. Immunol, 2006; 176:4075-4082.

Smith, J.A.; Marker-Hermann, E.; Colbert, R.A.: Pathogenesis of ankylosing spondylitis: current concepts.Best Prac Res Clin Rheumatol, 2006; 20: 571-591.

Ward, M.M.; Bruckel, J.; Colbert, R.; Deodhar, A.; Emerson, C.; Genant, H.; Gladman, D.D.; Inman, R.; Reveille, J.; Sandborg, C.; Weisman, M.H.; Davis, J.C.: Summary of the 2005 Annual Research and Education Meeting of the Spondyloarthritis Research and Therapy Network (SPARTAN).J. Rheum, 2006; 33:978-982.

Turner, M.J.; Sowders, D.P.; DeLay, M.L.; Mohapatra, R.; Bai, S.; Smith, J.A.; Brandewie, J.R.; Taurog, J.D.; Colbert, R.A.: HLA-B27 misfolding in transgenic rats is associated with activation of the unfolded protein response.J. Immunol, 2005; 175:2438-2448.

Duffy, C.M.; Colbert, R.A.; Laxer, R.M.; Schanberg, L.E.; Bowyer, S.L.: Nomenclature and classification in chronic childhood arthritis: Time for a change?Arthritis Rheum, 2005; 52:382-385.

Colbert, R.A.: The immunobiology of HLA-B27: Variations on a theme.Curr. Mol. Med., 2004; 4:21-30.

Barnes, M.G.; Aronow, B.J.; Luyrink, L.K.; Moroldo, M.B.; Pavlidis, P.; Passo, M.H.; Grom, A.A.;Hirsch, R.; Giannini, E.H.; Colbert, R.A.; Glass, D.N.; Thompson, S.D.: Gene expression in juvenile arthritis and spondyloarthropathy: pro-angiogenic ELR+ chemokine genes relate to course of arthritis.Rheumatology (Oxford), 2004; 43:973-9.

Penttinen, M.A.; Heiskanen, K.M.; Mohapatra, R.; DeLay, M.L.; Colbert, R.A.; Sistonen, L.; Granfors, K.: Enhanced intracellular replication of Salmonella enteritidis in HLA-B27-expressing human monocytic cells: dependency on Glu at position 45 in the B pocket of HLA-B27.Arthritis Rheum, 2004; 50:2255-63.

Presentations, Most Recent:

Colbert, R.A.: XBP-1 Links Protein Misfolding and Endoplasmic Reticulum Stress to Synergistic Type I Interferon Induction in Response to Toll-Like Receptor Ligands: Implications for HLA-B27-Associated Disease. Presented at the Fifthe International Congress on Spondyloarthropathies; October 12-14, 2006; Ghent, Belgium.

Colbert, R.A.: (i) Advances in the Genomics of Pediatric Rheumatic Disease, (ii) Genetic Susceptibility to Pediatric Rheumatic Disease, and (iii) Spondyloarthritis in Children: Pathogenesis and Recognition of Early Disease. Presented at the PANLAR International Rheumatology Meeting; August 18-22, 2006, Lima, Peru.

Colbert, R.A.: HLA-B27 and Spondyloarthritis: The Unfolding Story. Presented at Oregon Health Sciences University, Rheumatology Grand Rounds; January, 2006.

Colbert, R.A.: JRA, Systemic Onset JRA, Macrophage Activation Syndrome: When to Worry. Presented at Oregon Health Sciences University, City-Wide Rheumatology Grand Rounds; January, 2006.

Colbert, R.A.: Update on the Immunobiology of HLA-B27. Presented at the SPARTAN Annual Meeting; August, 2005, San Francisco, CA.

Colbert, R.A.: Spondyloarthritis: Update on Treatment, Genetics, and Pathogenesis. Presented at the Hospital for Special Surgery and the Cornell University Weill Medical College of Medicine Rheumatology Grand Rounds; April, 2005, New York, NY.

Colbert, R.A.: Pediatric Rheumatic Disease: Will Microarrays Answer Macro Questions? Presented as the 11th Abe Shore Lecture, Pediatric Grand Rounds, The Hospital for Sick Children; January, 2004, Toronto, ON, Canada.