John Elliott, MD/PhD
Office: 6-002B Li Ka Shing Centre for Health Research Innovation
Mail: University of Alberta, Edmonton AB, T6G 2E1
Professor, Department of Medical Microbiology & Immunology
Molecular immunology of autoimmune diseases
For many years we have collaborated with islet transplant researchers in the ADI to develop gene therapy approaches to promote the survival of islets after they have been transplanted.
Current Research Activities
Our work focuses on characterizing the cellular and molecular mechanisms that trigger human autoimmune diseases like type 1 diabetes, idiopathic myocarditis, and psoriasis. We would like to understand what goes wrong with the immune system and how it allows tissue damage to occur.
Human immune regulatory genes, particularly certain variants of HLA (=MHC) genes appear to play a critical role in autoimmune diseases, and we have created a series of human MHC Class II (DQ) transgenic NOD mice to further study this phenomenon. This has enabled us to create several completely new mouse models for common human autoimmune diseases. Information gained by studying these mice can now be used to guide immunological studies in patients.
Through collaboration with colleagues at the Sanger
Center in Cambridge UK we have helped determine the complete DNA sequence of several human MHC regions. This provides a critical ‘road map’ of all of the genes in a key part of the genome that contributes to autoimmune disease etiology. This work is now focused on determining the MHC sequence from someone who actually has type 1 diabetes.
BMedSci, MD, PhD
Marttila J, Huttunen S, Vaarala O, Suzuki K, Elliott JF, Narvanen A, Knip M, Simell O, Ilonen, J. T-cell reactivity to insulin peptide A1-12 in children with recently diagnosed type 1 diabetes or multiple beta-cell autoantibodies. J of Autoimmun. In Press.
Horton R, Gibson R, Coggill P, Miretti M, Allcock RJ, Almeida J, Forbes S, Gilbert JG, Halls K, Harrow JL, Hart E, Howe K, Jackson DK, Palmer S, Roberts AN, Sims S, Stewart CA, Traherne JA, Trevanion S, Wilming L, Rogers J, de Jong PJ, Elliott JF, Sawcer S, Todd JA, Trowsdale J, Beck S. Variation analysis and gene annotation of eight MHC haplotypes: the MHC Haplotype Project. Immunogenetics. 2008 Jan;60(1):1-18.
M Nakayama JN Beilke, JM Jasinski, M Kobayashi, D Miao, M Li, MG Coulombe, E Liu, JF Elliott, RG Gill, GS Eisenbarth. NOD Islet autoimmunity—Priming and Effector Dependence on Insulin. B:9-23 Peptitde. J Clin Invest. 2007 Jul 2;117(7):1835-1843.
P van de Linde, PJ Boog, OM Tysma, JF Elliott, DL Roelen, FH Claas, JW Fijter, BO Roep. Immunotherapy with antibodies to protect beta cells in type 1 diabetic pancreas transplant recipients. Clin Exp Immunol. 2007 Jul;149(1):56-62. Epub 2007 Apr 25.
SL Hayward, K Suzuki, JF Elliott. A Radioligand Binding Assay to Measure Anti-Thyroperoxidase Autoantibodies in Mice. J Immunol Methods. 2007 Jun 30;323(2):114-22. Epub 2007 Apr 30.
F Dotta, S Censini, AG van Halteren, L Marselli, M Masini, S Dionisi, F Mosca, U Boggi, AO Muda, SD Prado, JF Elliott, A Covacci, R Rappuoli, BO Roep, P Marchetti. Coxsackle B4 virus infection of beta cells and natural killer cell insulitis in recent-onset type 1 diabetic patients. Proc. Natl. Acad. Sci. USA. 20;(12)5115-20, March 20, 2007.
M Nakayama, N Babaya, D Miao, R Gianini, E Liu, JF Elliott, GS Eisenbarth. Long-term Prevention of Diabetes and Marked Suppression of Insulin Autoantibodies and Insulitis in Mice lacking Native Insulin. B9-23 Sequence. Ann. N. Y. Accad. Sci. 1079:122-9, October, 2006.
B Faideau, C Lotton, B Lucas, I Tardivel, JF Elliott, C Boitard, J-C Carel. Tolerance to proinsulin-2 is due to Radioresistant thymic cells. J Immunol. 177;(1):53-60, July 1, 2006.
JA Emamaullee, RV Rajotte, G Korbutt, JF Elliott. Neonatal Porcine Islets Exhibit Natural Resistance to Hypoxia Induced Apoptosis. Transplantation. 82(7):945-952, October 15, 2006.
SL Hayward, N Bautista-Lopez, K Suzuki, A Atrazhev, P Dickie, JF Elliott. CD4 T Cells Play Major Effector Role and CD8 T Cells Initiating Role in Spontaneous Autoimmune Myocarditis of HLA-DQ8 Transgenic IAb Knockout Nonobese Diabetic Mice. J. Immunol. 176(12): 7715-25, June 15, 2006.
JA Traherne, R Horton, AN Roberts, MM Miretti, ME Hurles, CA Stewart, JL Ashurst, AM Atrazhev, P Coggill, S Palmer, J Almeida, S Sims, LG Wilming, J Rogers, PJ de Jong, M Carrington, JF Elliott, S Sawcer, JA Todd, J Trowsdale, S Beck. Genetic Analysis of Completely Sequenced Disease-Associated MHC Haplotypes Identifies Shuffling of Segments in Recent Human History. PLoS Genetics. (1):1-12, January 27, 2006.
JA Emamaullee, RV Rajotte, P Liston, RG Korneluk, JRT Lakey, AMJ Shapiro, JF Elliott. XIAP Overexpression in Human Islets Prevents Early Posttransplant Apoptosis and Reduces the Islet Mass Needed to Treat Diabetes. Diabetes. 54(9):2541-8, September 2005.
M Nakayama, N Abiru, H Moriyama, N Babaya, E Liu, D Miao, L Yu, DR Wegmann, JC Hutton, JF Elliott, GS Eisenbarth. Prime role for an insulin epitope in the development of type 1 diabetes in NOD mice. Nature. 435(7039):220-3, May 12, 2005.
JA Emamaullee, P Liston, RG Korneluk, AMJ Shapiro, JF Elliott. XIAP Overexpression in Islet b-cells Enhances Engraftment and Minimized Hypoxia-Reperfusion Injury. Am J Transplant. 5(6):1297-305, June 2005.
CA Stewart, R Horton, RJ Allcock, J Ashurst, AM Atrazhev, P Coggill, I Dunham, S Forbes, K Halls, JM Howson, SJ Humphray, S Hunt, AJ Mungall, K Osoegawa, AN Roberts, J Rogers, S Sims, Y Wang, S Palmer, LG Wilming, JF Elliott, PJ de Jong, S Sawcer, JA Todd, J Trowsdale, S Beck. Complete MHC Haplotype Sequencing for Common Disease Gene Mapping. Genome Res. 14(6):1176-87, June 2004.
JF Elliott, J Liu, ZN Yuan, N Bautista-Lopez, SL Wallbank, K Suzuki, D Rayner, P Nation, MA Robertson, G Liu, KM Kavanagh. Autoimmune cardiomyopathy and heart block develop spontaneously in HLA-DQ8 transgenic IAbeta knockout NOD mice. Proc Natl Acad Sci USA. Nov 100(23):13447-52, November 11, 2003.
MA Craig, JF Elliott. Mice fed radiolabeled protein by gavage show sporadic passage of large quantities of intact material into the bloodstream, an artifact not seen with voluntary feeding. Contemp Top Lab Anim Sci. 38(5):18-23, September 1999.
J Liu, LE Purdy, S Rabinovitch, AM Jevnikar, JF Elliott. Major DQ8-restricted T-cell epitopes for human GAD65 mapped using human CD4, DQA1*0301, DQB1*0302 transgenic IA(null) NOD mice. Diabetes. 48(3):469-77, March 1999.
JF Elliott. New approaches to preventing and treating Type 1 Diabetes: Discovering a method to preserve beta cell mass after diagnosis should remain a key research focus. Can J Diabetes Care. 22(3):S24-30, 1998.
JF Elliott, KL Marlin, RM Couch. Effect of Calmette-Guerin vaccination on C-peptide secretion in newly diagnosed children with IDDM. Diabetes Care. 21(10):1691-3, October 1998.
AL Gainer, WL Suarez-Pinzon, WP Min, JR Swiston, C Hancock-Friesen, GS Korbutt, RV Rajotte, GL Warnock, JF Elliott. Improved survival of biolistically transfected mouse islet allografts expressing CTLA4-Ig or soluble Fas ligand. Transplantation. 66 (2):194-9, July 27 1998.
KS Ronningen, A Atrazhev, L Luo, C Luo, DK Smith, GS Korbutt, RV Rajotte, JF Elliott. Anti-BSA antibodies do not cross-react with the 69-kDa islet cell autoantigen ICA69. J of Autoimmun. 11(3):223-31, June 1998.
DK Smith, GS Korbutt, WL Suarez-Pinzon, D Kao, RV Rajotte, JF Elliott. Interleukin-4 or interleukin-10 expressed from adenovirus-transduced syngeneic islet grafts fails to prevent beta cell destruction in diabetic NOD mice. Transplantation. 64(7):1040-49, October 1997.
AL Gainer, GS Korbutt, RV Rajotte, GL Warnock, JF Elliott. Expression of CTLA4-Ig by biolistically transfected mouse islets promotes islet allograft survival. Transplantation. 63(7):1017-21, April 15, 1997.
MA Craig, JF Elliott. HLA-DQA1 genotyping by bi-directional sequencing of PCR-amplified DNA spanning exon 2. Tissue Antigens. 49(4):417-20, April 1997.
GS Korbutt, JF Elliott, RV Rajotte. Cotransplantation of allogeneic islets with allogeneic testicular cell aggregates allows long-term graft survival without systemic immunosupression. Diabetes. 46(2):317-22, February 1997.
AL Gainer, GS Korbutt, RV Rajotte, GL Warnock, JF Elliott. Successful biolistic transformation of mouse pancreatic islets while preserving cellular function. Transplantation. 61(11):1567-71, June 15, 1996.
JF Elliott, HY Qin, S Bhatti, DK Smith, RK Singh, T Dillon, J Lauzon, B Singh. Immunization with the larger isoform of mouse glutamic acid decarboxylase (GAD67) prevents autoimmune diabetes in NOD mice. Diabetes. 43(12):1494-9, December, 1994.
AY Lin, B Devaux, A Green, C Sagerström, JF Elliott, MM Davis. Expression of T-cell antigen receptor heterodimers in a lipid-linked form. Science. 249(4969):677-9, August 10, 1990.
JF Elliott, GR Albrecht, A Gilladoga, SM Handunnetti, J Neequaye, G Lallinger, JN Minjas, RJ Howard. Genes for Plasmodium falciparum surface antigens cloned by expression in COS cells. Proc Natl Acad Sci USA. 87(16):6363-7, August 1990.
EY Loh, JF Elliott, S Cwirla, LL Lanier, MM Davis. Polymerase chain reaction with single-sided specificity: analysis of T cell receptor delta chain. Science. 243(4888): 217-20, January 13, 1989.
JF Elliott, EP Rock, PA Patten, MM Davis, YH Chien. The adult T-cell receptor delta-chain is diverse and distinct from that of fetal thymocytes. Nature. 331(6157): 627-31, February 18, 1988.