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MICaB Faculty

 

Bryce A. Binstadt

Bryce A. Binstadt, M.D., Ph.D.

Associate Professor

Department of Pediatrics

Mayo Medical School, 1999, M.D.
Mayo Graduate School, 1999, Ph.D.

Lab phone: 612-626-9684
Office phone: 612-625-2953

E-mail:binstadt@umn.edu


Research Interests:

Autoimmunity, Innate Immunity

The Binstadt Laboratory is broadly interested in autoimmune disease pathogenesis. 

One main line of investigation focuses on how systemic autoimmune diseases lead to cardiovascular inflammation and damage.  We use the K/BxN T cell receptor (TCR) transgenic mouse model.  K/BxN mice spontaneously develop both inflammatory arthritis and autoimmune valvular carditis.  We use this model to study the effector pathways driving the cardiac valve inflammation.  Current projects seek to understand the key contributions of macrophage subsets and cytokines in this model.

A second line of research focuses on the potential role of dual TCR T cells in the development of autoimmune diseases.  Ongoing projects are focused on a) the contribution of dual TCR T cells to type I diabetes and other autoimmune diseases and b) engineering a dual TCRα reporter mouse.

Finally, new projects seek to understand the contribution of the nervous system to inflammatory arthritis, using the K/BxN serum-transferred arthritis model.

Clinical website - Division of Pediatric Rheumatology

Basic Science Publications:

  • Auger JL, Cowan HM, Engelson BJ, Kashem SW, Prinz I, Binstadt, BA. 2016. Arthritis in KRN T cell receptor transgenic mice does not require interleukin-17 or Th17 cells. Arthritis Rheumatol doi: 10.1002/art.39646. [Epub ahead of print]
  • Schuldt NJ, Auger JL, Hogquist KA, Binstadt BA. 2015. Bi-Allelic TCRα or β Recombination Enhances T Cell Development but Is Dispensable for Antigen Responses and Experimental Autoimmune Encephalomyelitis. PLoS One, 10(12):e0145762.
  • Hobday PM, Auger JL, Schuneman GR, Haasken S, Verbeek JS, Binstadt BA. 2014. Fcγ Receptor III and Fcγ Receptor IV on Macrophages Drive Autoimmune Valvular Carditis in Mice. Arthritis Rheumatol. 66(4):852-62.
  • Pauken KE, Linehan JL, Spanier JA, Sahli NL, Kalekar LA, Binstadt BA, Moon JJ, Mueller DL, Jenkins MK, Fife BT. 2013. Cutting Edge: Type 1 Diabetes Occurs Despite Robust Anergy Among Endogenous Insulin-Specific CD4 T Cells in NOD Mice. J Immunol. 191(10):4913-7.
  • Wang Y, Shaked I, Stanford SM, Zhou W, Curtsinger JM, Mikulski Z, Shaheen ZR, Cheng G, Sawatzke K, Campbell AM, Auger JL, Bilgic H, Shoyama FM, Schmeling DO, Balfour HH Jr, Hasegawa K, Chan AC, Corbett JA, Binstadt BA, Mescher MF, Ley K, Bottini N, Peterson EJ. 2013. The autoimmunity-associated gene PTPN22 potentiates toll-like receptor-driven, type 1 interferon-dependent immunity. Immunity. 25;39(1):111-22.
  • Haasken S, Auger JL, Taylor JJ, Hobday PM, Goudy BD, Titcombe PJ, Mueller DL, Binstadt BA. 2013. Macrophage Scavenger Receptor 1 (Msr1, SR-A) Influences B Cell Autoimmunity by Regulating Soluble Autoantigen Concentration. J. Immunol. 191(3):1055-62.
  • Auger, J.L., Haasken, S.S., Binstadt, B.A. 2012. Autoantibody-mediated arthritis in the absence of C3 and activating Fcgamma receptors: C5 is activated by the coagulation cascade. Arthritis Res. Ther. 14(6):R269.
  • Auger, J. L., Haasken, S., Steinert, E. M. and Binstadt, B. A. 2012. Incomplete TCR-β allelic exclusion accelerates spontaneous autoimmune arthritis in K/BxN TCR transgenic mice. Eur. J. Immunol.. doi: 10.1002/eji.201242520
  • Rao SM, Auger JL, Gaillard P, Weissleder R, Wada E, Torres R, Kojima M, Benoist C, Mathis D, Binstadt BA. 2012. The neuropeptide neuromedin U promotes autoantibody-mediated arthritis. Arthritis Res Ther.14(1):R29.
  • Haasken SS, Hebert JL, Binstadt BA. Absence of b2 integrins impairs regulatory T Cells and exacerbates CD4+ T cell-dependent autoimmune carditis. J. Immunol. Prepublished online 27 July 2011, doi:10.4049/jimmunol.1000967
  • Binstadt, BA, Hebert JL, Ortiz-Lopez A, Bronson R, Benoist C, Mathis D. 2009. The same systemic autoimmune disease provokes arthritis and endocarditis via distinct mechanisms. Proc Natl Acad Sci USA 106:16758-63.
  • Wu HJ, Sawaya H, Binstadt B, Brickelmaier M, Blasius A, Gorelik L, Mahmood U, Weissleder R, Carulli J, Benoist C, Mathis D. 2007. Inflammatory arthritis can be reined in by CpG-induced DC NK cell cross talk. J Exp Med 204: 1911-22.
  • Nigrovic PA, Binstadt BA, Monach PA, Johnsen A, Gurish M, Iwakura Y, Benoist C, Mathis D, Lee DM. 2007. Mast cells contribute to the initiation of autoantibody-mediated arthritis via IL-1. Proc Natl Acad Sci USA 104: 2325-30.
  • Binstadt BA, Patel PR, Alencar H, Nigrovic PA, Lee DM, Mahmood U, Weissleder R, Mathis D, Benoist C. 2006. Particularities of the vasculature can promote the organ specificity of autoimmune attack. Nat Immunol 7: 284-92.
  • Binstadt BA, Billadeau DD, Jevremovic D, Williams BL, Yi T, Koretzky GA, Abraham RT, Leibson PJ. 1998. SLP-76 is a direct substrate of SHP-1 recruited to killer cell inhibitory receptors. J Biol Chem 273: 27518-23.
  • Brumbaugh KM, Binstadt BA, Billadeau DD, Schoon RA, Dick CJ, Ten RM, Leibson PJ. 1997. Functional role for Syk tyrosine kinase in NK cell-mediated natural cytotoxicity. J Exp Med 186: 1965-74.
  • Binstadt BA, Brumbaugh KM, Dick CJ, Scharenberg AM, Williams BL, Colonna M, Lanier LL, Kinet J-P, Abraham RT, Leibson PJ. 1996. Sequential involvement of Lck and SHP-1 with MHC-recognizing receptors on NK cells inhibits FcR-initiated tyrosine kinase activation. Immunity 5: 629-38.
  • Einspahr KJ, Abraham RT, Binstadt BA, Uehara Y, Leibson PJ. 1991. Tyrosine phosphorylation provides an early and requisite signal for the activation of natural killer cell cytotoxic function. Proc Natl Acad Sci USA 88: 6279-83.

 

Clinical Publications:

  • Correll CK, Binstadt BA. 2014. Advances in the pathogenesis and treatment of systemic juvenile idiopathic arthritis. Pediatr Res. 75(1-2):176-83.
  • Breunig A, Lee MS, Mille, BS, Binstadt BA, Anderson MS, Montezume S. 2013. Autoimmune retinopathy in a patient with autoimmune polyendocrine syndrome type I. Ocul Immunol Inflamm 21(1):153-7.
  • Taxter AJ, Bellin MD, Binstadt BA. Pericarditis as the presenting feature of adrenoleukodystrophy. Pediatrics, 2011; 127: e771-4.
  • Stingl C, Moller JH, Binstadt BA. 2009. Cardiac Operations for North American Children with Rheumatic Diseases: 1985-2005. Pediatr Cardiol. (Epub ahead of print).
  • Zhang K, Biroschak J, Glass DN, Thompson SD, Finkel T, Passo MH, Binstadt BA, Filipovich A, Grom AA. 2008. Macrophage activation syndrome in patients with systemic juvenile idiopathic arthritis is associated with MUNC13-4 polymorphisms. Arthritis Rheum. 58(9):2892-6.
  • Hazen MM, Woodward AL, Hofmann I, Degar BA, Grom A, Filipovich AH, Binstadt BA. 2008. Mutations of the hemophagocytic lymphohistiocytosis-associated gene UNC13D in a patient with systemic juvenile idiopathic arthritis. Arthritis Rheum.58(2):567-570 [Epub ahead of print]
  • El-Hallak M*, Binstadt BA*, Leichtner AM, Bennett CM, Neufeld EJ, Fuhlbrigge RC, Zurakowski D, Sundel RP. 2007. Clinical effects and safety of rituximab for treatment of refractory pediatric autoimmune diseases. J Pediatr 150: 376-82. *Shared first-authorship
  • St. Clair NE, Kim CC, Semrin G, Woodward AL, Liang MG, Glickman JN, Leichtner AM, Binstadt BA. 2006. Celiac disease presenting with chilblains in an adolescent girl. Pediatr Dermatol 23: 451-4.
  • Binstadt BA, Levine JC, Nigrovic PA, Gauvreau K, Dedeoglu F, Fuhlbrigge RC, Weindling SN, Newburger JW, Sundel RP. 2005. Coronary artery dilation among patients presenting with systemic-onset juvenile idiopathic arthritis. Pediatrics 116: e89-93.
  • Almond CSD, Shin AY, Fortescue EB, Mannix RC, Wypij D, Binstadt BA, Duncan CN, Olson DP, Salerno AE, Newburger JW, Greenes DS. 2005. Hyponatremia among runners in the Boston Marathon. N Engl J Med 352:1550-6.
  • Binstadt BA, Fleegler EW. 2005. Perforated appendicitis in a child with Henoch-Schönlein purpura. J Pediatr Surg 40: e24-27.
  • Binstadt BA, Caldas AM, Turvey SE, Stone KD, Weinstein HJ, Jackson J, Fuhlbrigge RC, Sundel RP. 2003. Rituximab therapy for multisystem autoimmune diseases in pediatric patients. J Pediatr 143: 598-604.