Jane Buckner, MD

Title:

Member and Program Director, Translational Research, Associate Director BRI

Phone Number:

(206) 341-0097, (206) 287-1033

Background

Dr. Buckner received her bachelor’s degree in chemistry from Carleton College, magna cum laude. She attended Johns Hopkins School of Medicine, and after receiving her MD she completed her residency training in Internal Medicine at the University of Minnesota. Dr. Buckner went on to complete a fellowship in Rheumatology at the University of Washington. As a fellow she was honored with the American College of Rheumatology’s Senior Rheumatology Scholar Award. After completing her medical training, Dr. Buckner continued her research training as a postdoctoral fellow in the laboratory of Dr. Gerald Nepom. In 1999, she was the recipient of the ACR Arthritis Investigator Award. Since 1999, Dr. Buckner has been an investigator at the Benaroya Research Institute and in 2012 became Associate Director of BRI.

Areas of Research

Dr. Buckner’s laboratory is focused on identifying the underlying mechanisms by which regulation of the adaptive immune response fails or is overcome in the setting of human autoimmunity. The diseases studied in Dr. Buckner’s laboratory include Type 1 diabetes, multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosis and relapsing polychondritis. Her laboratory is currently examining the question of how autoreactive T and B cells escape regulation in these diseases and the closely related question of whether the development or function of adaptive Tregs is impaired in autoimmunity. Recently, her group has expanded their focus by utilizing the genetics of autoimmunity to identify the pathways that contribute to these defects. Initial studies have focused on the impact of the PTPN22 1858T variant on lymphocyte function. This work is aided by the availability of human samples for research, which are collected from individuals participating in the Immune Mediated Disease Registry and Repository managed by the Translational Research Program at BRI. This resource provides samples from subjects who are well characterized in terms of clinical characteristics for cellular, biochemical and genetic analysis.

In 2005, Dr. Buckner became the Director of Translational Research at BRI. The goal of this program is to encourage and facilitate research into human immune diseases. Dr. Buckner sees patients with rheumatic diseases at the Virginia Mason Clinic and at the University of Washington as a clinical assistant professor.

Selected Publications

Buckner J, Kwok WW, Nepom B, Nepom GT.  Modulation of HLA-DQ binding properties by differences in class II dimer stability and pH-dependent peptide interactions. J Immunol. 1996; 157:4940-45.

Buckner JH, Wu JJ, Riefe RA, Terato K, Eyre DR. Autoreactivity against matrilin 1 in a patient with relapsing polychondritis. Arthritis Rheum. 2000; 43:939-43.

Gebe JA, Novak EJ, Kwok WW, Farr AG, Nepom GT, Buckner JH.  T cell selection and differential activation on structurally related HLA-DR4 ligands. J Immunol. 2001; 167:3250-56.

Buckner JH, Van Landeghen M, Kwok WW, Tsarknaridis L. Identification of type II collagen (261-273) specific T cell clones in a patient with relapsing polychondritis. Arthritis Rheum. 2002; 46:238-44.

Buckner JH, Nepom GT. Genetics of rheumatoid arthritis: is there a scientific explanation for the human leukocyte antigen association? Curr Opin Rheumatol. 2002; 14:254-59.

Buckner JH, Holzer U, Novak EJ, Reijonen H, Kwok WW, Nepom GT. Defining antigen-specific responses with human MHC class II tetramers. J Allergy Clin Immunol. 2002; 110:199-208.

Kwok WW, Ptacek NA, Liu AW, Buckner JH. Use of class II tetramers for identification of CD4+ T cells. J Immunol Methods. 2002; 268:71-81.

Holzer U, Kwok WW, Nepom GT, Buckner JH. Differential antigen sensitivity and costimulatory requirements in human Th1 and Th2 antigen specific CD4+ cells with similar TCR avidity. J Immunol. 2003; 170:1218-23.

Walker MR, Kasprowicz D, Gersuk B, Benard A, Van Landeghen M, Buckner J, Ziegler S. Induction of FoxP3 and acquisition of T regulatory activity by stimulated human CD4+CD25- T cells. J Clin. Invest. 2003; 112:1437-43.

Buckner JH, Nepom GT.  Structure, function, and genetics of the human leukocyte antigen complex in rheumatic disease.  In: Arthritis and Allied Conditions; Fifteenth Edition, W.J. Koopman and L. W. Moreland, eds. Lippincott Williams and Wilkins 2005.

Walker MR, Carson BD, Nepom GT, Ziegler SF, Buckner JH. De novo generation of antigen-specific CD4+CD25+ regulatory T cells from human CD4+CD25- cells. Proc Natl Acad Sci U.S.A. 2005; 102:4103-08.

Holzer U, Rieck M, Buckner JH. Lineage and signal strength determine the inhibitory effect of transforming growth factor b1 (TGFb1) on human antigen-specific Th1 and Th2 memory cells. J Autoimmun. 2006; 26:241-51, Epub 2006.

Onengut-Gumuscu S, Buckner JH, Concannon P. A haplotype-based analysis of the PTPN22 locus in type 1 diabetes. Diabetes. 2006; 55:2883-9.

Rieck M, Arechiga A, Onegut-Gumuscu S, Greenbaum C, Concannon P, Buckner JH. Genetic variation in PTPN22 corresponds to altered function of T and B lymphocytes. J. Immunology 2007 Oct 1;179(7):4704-10.

Long, SA and Buckner, JH. Combination of Rapamycin and IL-2 increases de novo induction of human CD4+CD25+FOXP3+ T cells. J of Autoim. 2008 Jun:30(4):293-302.

Schneider A, Rieck M, Sanda S,  Pihoker C, Greenbaum C, Buckner JH. The effector T cells of diabetic subjects are resistant to regulation via CD4+FOXP3+ Treg. J Immunol. 2008 Nov 15;181(10):7350-5.

Long SA, Walker MR, Rieck M, James EA, Kwok WW, Sanda S, Pihoker C, Greenbaum C, Nepom GT, Buckner JH. Functional Islet-Specific Treg Can Be Generated from CD4+CD25- T cells of Healthy and Type 1 Diabetic Subjects. Eur J Immunol. 2009 Feb;39(2):612-20.

Arechiga A, Habib T, He Y, Zhang X, Zhang Z-Y, Funk A, Buckner JH. Cutting Edge: The PTPN22 allelic variant associated with autoimmunity impairs B cell signaling. J Immunol. 2009 Mar 15;182(6):3343-7.

Kolfenbach JR, Deane KD, Derber LA, O’Donnell C, Weisman MH, Buckner JH, Gersuk VH, Wei S, Mikuls TR, O’Dell J, Gregersen PK, Keating RM, Norris JM, Holers VM.         A prospective approach to investigating the natural history of preclinical rheumatoid arthritis (RA) using first-degree relatives of probands with RA. Arthritis Rheum. 2009 Nov 30;61(12):1735-1742.

Long SA, Cerosaletti K, Bollyky PL, Tatum M, Shilling H, Zhang S, Zhang Z, Pihoker C, Sanda S, Greenbaum C and Buckner JH. Defects in IL-2R signaling contribute to diminished maintenance of FOXP3 expression in CD4+CD25+ regulatory T cells of T1D subjects. Diabetes. 2010 Feb;59(2):407-15.

James EA, Moustakas AK, Bui J, Papadopoulos GK, Bondinas G, Buckner JH, Kwok WW. HLA-DR1001 presents 'altered-self' peptides derived from joint associated proteins by accepting citrulline in three of its binding pockets. Arthritis Rheum. 2010 Oct;62(10):2909-18.

Buckner JH. Mechanisms of impaired regulation by CD4(+)CD25(+)FOXP3(+) regulatory T cells in human autoimmune diseases. Nat Rev Immunol. 2010 Dec;10(12):849-59. Review.

Long SA, Cerosaletti K, Wan JY, Ho J-C, Tatum M, Wei S, Shilling HG, Buckner JH. An autoimmune-associated variant in PTPN2 reveals an impairment of IL-2R signaling in CD4+ T cells. Genes Immun. 2010 Dec. 23.

Schneider A, Buckner JH. Assessment of suppressive capacity by human regulatory T cells using a reproducible, bi-directional CFSE-based in vitro assay. Methods Mol Biol. 2011;707:233-41.

Snir O, Rieck M,  Gebe J, Yue B, Rawlings C, Nepom G, Malmström V, Buckner JH. Identification and function of T cells reactive to citrullinated-vimentin in HLA-DRB1*0401 humanized mice and rheumatoid arthritis patients. Arthritis and Rheumatism, in press.

Buckner Laboratory

Translational Research Program