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Jane Buckner, MD

Title:

BRI Associate Director, Member, and Program Director of the Translational Research Program

Phone Number:

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

Background

Dr. Buckner received her bachelor’s degree in chemistry from Carleton College. 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 Tregs is impaired in autoimmunity. Her group has utilized our knowledge of the genetics of autoimmunity to identify pathways that contribute to the failure of tolerance in these diseases. These studies have focused on the impact of the PTPN22 1858T variant on lymphocyte function and the demonstration that T1D risk variants in PTPN2 and CD25 contribute to diminished IL-2 signaling. 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

  1. Schneider A, Long  SA, Cerosaletti K, Ni CT, Samuels P, Kita M, Buckner JH. In active relapsing remitting multiple sclerosis, effector T cell resistance to adaptive Tregs involves IL-6-mediated signaling. Sci Transl Med. 2013 Jan 30;5(170):170ra15. doi: 10.1126/scitranslmed.3004970
  2. Long SA, Rieck M, Sanda S, Bollyky JB, Samuels PL, Goland R, Ahmann A, Rabinovitch A, Aggarwal S, Phippard D, Turka LA, Ehlers MR, Bianchine PJ, Boyle KD, Adah SA, Bluestone JA, Buckner J, Greenbaum CJ. Rapamycin/IL-2 combination therapy in type 1 diabetics augments Treg yet transiently impairs beta cell function. Diabetes. 2012 Jun 20. PMCID:3425404
  3. Roep BO, Buckner J, Sawcer S, Toes R, Zipp F. The problems and promises of research into human immunology and autoimmune disease. Nat Med. 2012 Jan 6;18(1):48-53. PMID: 22227672
  4. Habib T, Funk A, Rieck M, Brahmandam A, Dai X, Panigrahi A, Prak E, Meyer-Bahlmburg A, Sanda S, Greenbaum C, Rawlings D, Buckner JH. Altered B cell homeostasis is associated with Type I diabetes and carriers of the PTPN22 allelic variant, J Immunol. 2012 Jan 1; 487-96. In This Issue section of J Immunol. PMID:22105996
  5. Snir O, Rieck M,  Gebe J, Yue B, Rawlings C, Nepom G, Malmström V, Buckner JH. Identification and functional characterization of T cells reactive to citrullinated-vimentin in HLA-DRB1*0401 humanized mice and RA patients. Arthritis Rheum. 2011 Oct. 3(10):2873-83. PMCID:3174345
  6. Menard L, Saadoun D, Isnardi I, Ng YS, Meyers G, Massad C, Price C, Abraham C, Motaghedi R, Buckner JH, Gregersen PK, Meffre E. The PTPN22 allele encoding an R620W variant interferes with the removal of developing autoreactive B cells in humans. J Clin Invest. 2011 Sep 1;121 (9):3635-44. PMCID:21804190
  7. Long SA, Rieck M, Tatum M, Bollyky PL, Wu RP, Mueller I, Ho JC, Shilling HG, Buckner JH. Low-Dose Antigen Promotes Induction of FOXP3 in Human CD4+ T Cells. J Immunol. 2011 Oct 1; 3511-20. Epub 2011 Aug 24. PMCID:3178710
  8. 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. 2011 Mar;12 (2):116-25. PMCID:3058680
  9. 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. PMCID:3046807
  10. 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. PMCID:2809970
  11. 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. PMCID:19265110
  12. 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. PMCID:2743096
  13. 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. PMCID:2597079
  14. 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. PMCID:2431984
  15. 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. PMID: 17878369
  16. Onengut-Gumuscu S, Buckner JH, Concannon P. A haplotype-based analysis of the PTPN22 locus in type 1 diabetes. Diabetes. 2006; 55:2883-9.
  17. Holzer U, Rieck M, Buckner JH. Lineage and signal strength determine the inhibitory effect of transforming growth factor 1 (TGF1) on human antigen-specific Th1 and Th2 memory cells. J Autoimmun. 2006; 26:241-51, Epub 2006.
  18. 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
  19. 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.
  20. 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.
  21. 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.
  22. 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.
  23. 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.
  24. Nepom GT, Buckner JH, Novak EJ, Reichstetter S, Reijonen H, Gebe J, Wang R, Swanson E, Kwok WW. HLA class II tetramers: Tools for direct analysis of antigen-specific CD4+ T cells. Arthritis Rheum. 2002; 46:5-12.
  25. 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  

Buckner Laboratory

Translational Research Program