Welcome to the Steinman Lab
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About Us
Our laboratory is dedicated to understanding the pathogenesis of autoimmune diseases, particularly multiple sclerosis and neuromyelitis optica.
We have developed several new therapies for autoimmunity, including some in Phase 2 clinical trials in multiple sclerosis and type 1 diabetes mellitus, as well as one approved drug, natalizumab.
We have developed microarray technology for detecting autoantibodies to myelin proteins and lipids. We employ a diverse range of molecular and cellular approaches to devise new medications for demyelinating diseases, and to help predict which current medications will work at various stages of these diseases.
Publication highlights
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Antibodies to influenza nucleoprotein cross-react with human hypocretin receptor 2. Ahmed SS, Volkmuth W, Duca J, Corti L, Pallaoro M, Pezzicoli A, Karle A, Rigat F, Rappuoli R, Narasimhan V, Julkunen I, Vuorela A, Vaarala O, Nohynek H, Pasini FL, Montomoli E, Trombeta C, Adams CM, Rothbard J, Steinman L. Sci Transl Med. 2015 7, 294ra105.
- No Quiet Surrender: Molecular Guardians In Multiple Sclerosis Brain. Steinman L. J. Clin Invest. 2015 125:1371-1378.
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Mechanisms of action of therapeutic amyloidogenic hexapeptides in amelioration of inflammatory brain disease. Kurnellas, M. P., Schartner, J. M., Fathman, C. G., Jagger, A., Steinman, L., Rothbard, J. B. J. Exp. Med. 2014; 211 (9): 1847-1856.
- Immunology of Relapse and Remission in Multiple Sclerosis. Steinman L. Ann Rev Immunol. 2014 32:257-281.
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Plasmid-Encoded Proinsulin Preserves C-Peptide While Specifically Reducing Proinsulin-Specific CD8+ T Cells in Type 1 Diabetes. Roep BO, Solvason N, Gottlieb PA, Abreu JR, Harrison LC, Eisenbarth GS, Yu L, Leviten M, Hagopian WA, Buse JB, von Herrath M, Quan J, King RS, Robinson WH, Utz PJ, Garren H; BHT-3021 Investigators, Steinman L. Sci Transl Med. 2013 Jun 26;5(191):191ra82.
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Amyloid fibrils composed of hexameric peptides attenuate neuroinflammation. Kurnellas MP, Adams CM, Sobel RA, Steinman L, Rothbard JB. Sci Transl Med. 2013 Apr 3;5(179):179ra42
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The Gender Gap in Multiple Sclerosis: Intersection of Science and Society. Dunn SE, Steinman L. JAMA Neurol. 2013 Mar 4:1-2.
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A Tip leads cytotoxic T cells to the crime scene in neuroinflammation. Steinman L. Nat Immunol. 2013 Feb 15;14(3):196-7.
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Weighing In On Autoimmune Disease: 'Hub-and-spoke' T cell traffic in autoimmunity. Steinman L. Nat Med. 2013 Feb;19(2):139-41.
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Inflammatory cytokines at the summits of pathological signal cascades in brain diseases. Steinman L. Sci Signal. 2013 Jan 15;6(258):pe3.
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Piet Mondrian's trees and the evolution in understanding multiple sclerosis, Charcot Prize Lecture 2011. Steinman L, Axtell RC, Barbieri D, Bhat R, Brownell SE, de Jong BA, Dunn SE, Grant JL, Han MH, Ho PP, Kuipers HF, Kurnellas MP, Ousman SS, Rothbard JB. Mult Scler. 2013 Jan;19(1):5-14.
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Natalizumab: bench to bedside and beyond. Rudick R, Polman C, Clifford D, Miller D, Steinman L. JAMA Neurol. 2013 Feb 1;70(2):172-82.
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The discovery of natalizumab, a potent therapeutic for multiple sclerosis. Steinman, L. J Cell Biol. 2012 Oct 29;199(3):413-6.
- Chaperone activity of small heat shock proteins underlies therapeutic efficacy in experimental autoimmune encephalomyelitis. Kurnellas MP, Brownell SE, Su L, Malkovskiy AV, Rajadas J, Dolganov G, Chopra S, Schoolnik GK, Sobel RA, Webster J, Ousman SS, Becker RA, Steinman L, Rothbard JB. J Biol Chem. 2012 Oct 19;287(43):36423-34.
- Reversal of Paralysis and Reduced Inflammation from Peripheral Administration of β-Amyloid in TH1 and TH17 Versions of Experimental Autoimmune Encephalomyelitis. Grant JL, Ghosn EE, Axtell RC, Herges K, Kuipers HF, Woodling NS, Andreasson K, Herzenberg LA, Herzenberg LA, Steinman L. Sci Transl Med. 2012; Aug 1;4(145):145ra105.
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Janus-like opposing roles of CD47 in autoimmune brain inflammation in humans and mice. Han MH, Lundgren DH, Jaiswal S, Chao M, Graham KL, Garris CS, Axtell RC, Ho PP, Lock CB, Woodard JI, Brownell SE, Zoudilova M, Hunt JF, Baranzini SE, Butcher EC, Raine CS, Sobel RA, Han DK, Weissman I, Steinman L. J Exp Med. 2012 Jul 2; 209(7):1325-34.
- Nostalgia: the similarities between immunological and neurological memory. Steinman L. Immunol Rev. 2012 Jul;248(1):5-9.
- Identification of naturally occurring fatty acids of the myelin sheath that resolve neuroinflammation. Ho PP, Kanter JL, Johnson AM, Srinagesh HK, Chang EJ, Purdy TM, van Haren K, Wikoff WR, Kind T, Khademi M, Matloff LY, Narayana S, Hur EM, Lindstrom TM, He Z, Fiehn O, Olsson T, Han X, Han MH, Steinman L, Robinson WH. Sci Transl Med. 2012; Jun 6;4(137):137ra73.
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Therapeutic Effects of Systemic Administration of Chaperone αlpha B-Crystallin Associated with Binding Proinflammatory Plasma Proteins. Rothbard JB, Kurnellas MP, Brownell S, Adams CM, Su L, Axtell RC, Chen R, Fathman CG, Robinson WH, Steinman L. J Biol Chem. 2012; 287(13):9708-21.
- Chaperone activity of alpha B-crystallin is responsible for its incorrect assignment as an autoantigen in multiple sclerosis. Rothbard JB, Zhao X, Sharpe O, Strohman MJ, Kurnellas M, Mellins ED, Robinson WH, Steinman L. J Immunol. 2011; 186 (7): 4263-8.
- T helper type 1 and 17 cells determine efficacy of interferon-beta in multiple sclerosis and experimental encephalomyelitis. Axtell RC, de Jong BA, Boniface K, van der Voort LF, Bhat R, De Sarno P, Naves R, Han M, Zhong F, Castellanos JG, Mair R, Christakos A, Kolkowitz I, Katz L, Killestein J, Polman CH, de Waal Malefyt R, Steinman L, Raman C. Nat Med. 2010; 16 (4): 406-12.
- Inhibitory role for GABA in autoimmune inflammation. Bhat R, Axtell R, Mitra A, Miranda M, Lock C, Tsien RW, Steinman L. Proc Natl Acad Sci U S A. 2010; 107 (6): 2580-5.
- Inverse vaccination, the opposite of Jenner's concept, for therapy of autoimmunity. Steinman L, J Intern Med. 2010; 267 (5): 441-51.
- Innate and adaptive autoimmunity directed to the central nervous system. Bhat R, Steinman L. Neuron. 2009; 64 (1): 123-32.
- PPAR-delta senses and orchestrates clearance of apoptotic cells to promote tolerance. Mukundan L, Odegaard JI, Morel CR, Heredia JE, Mwangi JW, Ricardo-Gonzalez RR, Goh YP, Eagle AR, Dunn SE, Awakuni JU, Nguyen KD, Steinman L, Michie SA, Chawla A. Nat Med. 2009; 15 (11): 1266-72.
- Blocking angiotensin-converting enzyme induces potent regulatory T cells and modulates TH1- and TH17-mediated autoimmunity. Platten M, Youssef S, Hur EM, Ho PP, Han MH, Lanz TV, Phillips LK, Goldstein MJ, Bhat R, Raine CS, Sobel RA, Steinman L. Proc Natl Acad Sci U S A. 2009; 106 (35): 14948-53.
- A molecular trio in relapse and remission in multiple sclerosis. Steinman L, Nat Rev Immunol. 2009; 9 (6): 440-7.
- Nuanced roles of cytokines in three major human brain disorders. Steinman L, J Clin Invest. 2008; 118 (11): 3557-63.
- Improved efficacy of a tolerizing DNA vaccine for reversal of hyperglycemia through enhancement of gene expression and localization to intracellular sites. Solvason N, Lou YP, Peters W, Evans E, Martinez J, Ramirez U, Ocampo A, Yun R, Ahmad S, Liu E, Yu L, Eisenbarth G, Leviten M, Steinman L, Garren H. J Immunol. 2008; 181 (12): 8298-307.
- Phase 2 trial of a DNA vaccine encoding myelin basic protein for multiple sclerosis. Garren H, Robinson WH, Krasulová E, Havrdová E, Nadj C, Selmaj K, Losy J, Nadj I, Radue EW, Kidd BA, Gianettoni J, Tersini K, Utz PJ, Valone F, Steinman L. Ann Neurol. 2008; 63 (5): 611-20.
- Proteomic analysis of active multiple sclerosis lesions reveals therapeutic targets. Han MH, Hwang SI, Roy DB, Lundgren DH, Price JV, Ousman SS, Fernald GH, Gerlitz B, Robinson WH, Baranzini SE, Grinnell BW, Raine CS, Sobel RA, Han DK, Steinman L. Nature. 2008; 451 (7182): 1076-81
- A rush to judgment on Th17. Steinman L, J Exp Med. 2008; 205 (7): 1517-22.
- Induction of antigen-specific tolerance in multiple sclerosis after immunization with DNA encoding myelin basic protein in a randomized, placebo-controlled phase 1/2 trial. Bar-Or A, Vollmer T, Antel J, Arnold DL, Bodner CA, Campagnolo D, Gianettoni J, Jalili F, Kachuck N, Lapierre Y, Niino M, Oger J, Price M, Rhodes S, Robinson WH, Shi FD, Utz PJ, Valone F, Weiner L, Steinman L, Garren H. Arch Neurol. 2007; 64 (10): 1407-15.
- Protective and therapeutic role for alphaB-crystallin in autoimmune demyelination. Ousman SS, Tomooka BH, van Noort JM, Wawrousek EF, O'Connor KC, Hafler DA, Sobel RA, Robinson WH, Steinman L. Nature. 2007; 448 (7152): 474-9.
- Peroxisome proliferator-activated receptor (PPAR)alpha expression in T cells mediates gender differences in development of T cell-mediated autoimmunity. Dunn SE, Ousman SS, Sobel RA, Zuniga L, Baranzini SE, Youssef S, Crowell A, Loh J, Oksenberg J, Steinman L. J Exp Med. 2007; 204 (2): 321-30.
- A brief history of T(H)17, the first major revision in the T(H)1/T(H)2 hypothesis of T cell-mediated tissue damage. Steinman L, Nat Med. 2007; 13 (2): 139-45.
- Osteopontin-induced relapse and progression of autoimmune brain disease through enhanced survival of activated T cells. Hur EM, Youssef S, Haws ME, Zhang SY, Sobel RA, Steinman L. Nat Immunol. 2007; 8 (1): 74-83.
- What went wrong in the natalizumab trials? Langer-Gould A, Steinman L. Lancet. 2006; 367 (9512): 708-10.
- Lipid microarrays identify key mediators of autoimmune brain inflammation. Kanter JL, Narayana S, Ho PP, Catz I, Warren KG, Sobel RA, Steinman L, Robinson WH. Nat Med. 2006; 12 (1): 138-43.
- Isoprenoids determine Th1/Th2 fate in pathogenic T cells, providing a mechanism of modulation of autoimmunity by atorvastatin. Dunn SE, Youssef S, Goldstein MJ, Prod'homme T, Weber MS, Zamvil SS, Steinman L. J Exp Med. 2006; 203 (2): 401-12.
- Treatment of autoimmune neuroinflammation with a synthetic tryptophan metabolite. Platten M, Ho PP, Youssef S, Fontoura P, Garren H, Hur EM, Gupta R, Lee LY, Kidd BA, Robinson WH, Sobel RA, Selley ML, Steinman L. Science. 2005; 310 (5749): 850-5.
- Design of effective immunotherapy for human autoimmunity. Feldmann M, Steinman L. Nature. 2005; 435 (7042): 612-9.
- Blocking adhesion molecules as therapy for multiple sclerosis: natalizumab. Steinman L, Nat Rev Drug Discov. 2005; 4 (6): 510-8.
Link to all publications for Lawrence Steinman
Funding
Guthy-Jackson Charitable Foundation
National Multiple Sclerosis Society
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