Professor Len Harrison

Details

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Division: Molecular Medicine

Research Overview

We study mechanisms of immune regulation in health and disease, in particular antigen-specific regulatory T cells and antigen-specific immunotherapy. Our research is directed towards the prevention of diabetes, a major public and personal health problem that in developed countries directly accounts for 10% of health expenditure.

Type 1 diabetes is an ideal paradigm for autoimmune disease prevention because it can now be detected years before clinical presentation. We found that proinsulin is a critical autoantigen targeted by the immune system in its attack on insulin-producing beta cells in the pancreas. Proof-of-concept mouse model and human studies led us to nasal insulin vaccination trials to prevent type 1 diabetes. In type 2 diabetes, evidence for innate and adaptive immune activation led us to inflammatory mediators of insulin resistance as potential therapeutic targets.   

Research Interests

  • Antigen-specific regulatory T cells: characterisation and mechanism of action
  • Signalling pathways that define T-cell function
  • Micro RNAs: role in T cells and disease
  • Inflammatory markers as mediators of insulin resistance
  • Pancreas stem cells as a source of insulin for the treatment of type 1 diabetes

Selected Publications

  1. Fourlanos S, Perry C, Gellert SA, Martinuzzi E, Mallone R, Butler J, Colman PG, Harrison LC (2011) Evidence that nasal insulin induces immune tolerance to insulin in adults with autoimmune diabetes. Diabetes 60:1237-45 PMID: 21307076 [PubMed - indexed for MEDLINE]
  2. Martinuzzi E, Afonso G, Gagnerault M-C, Naselli G, Mittag D, Combadière B, Boitard C, Chaput N, Zitvogel L, Harrison LC, Mallone R (2011) Accelerated co-cultured dendritic cells (acDCs) enhance antigen-specific T-cell responses. Blood 118:2128-37. PMID: 21715316 [PubMed - indexed for MEDLINE]
  3. Mittag D, Proietto AI, Loudovaris T, Mannering SI, Vremec D, Shortman K, Wu L, Harrison LC (2011). Human dendritic cell subsets from blood and spleen are similar in phenotype and function, but modified by donor health status. J Immunol 186:6207-17 PMID: 21515786 [PubMed - indexed for MEDLINE]
  4. Dromey JA, Lee BH, Yu H, Young HE, Thearle DJ, Jensen KP, Mannering SI, Harrison LC (2011). Generation and expansion of regulatory human CD4+ T-cell clones specific for pancreatic islet autoantigens. J Autoimmunity 36: 47-55 PMID: 21050716 [PubMed - indexed for MEDLINE]
  5. Wentworth JM, Naselli G, Brown WA, Doyle L, Wabitsch M, O’Brien PE, Harrison LC (2010). Pro-inflammatory CD11c+CD206+ adipose tissue macrophages are associated with insulin resistance in human obesity. Diabetes 59:1648-56. PMID: 20357360 [PubMed - indexed for MEDLINE]
  6. Honeyman MC, Stone NL, Falk BA, Nepom G, Harrison LC (2010). Evidence for molecular mimicry between human T cell epitopes in rotavirus and pancreatic islet autoantigens. J Immunol 184:2204-10. PMID: 20083660 [PubMed - indexed for MEDLINE]
  7. Wentworth JM, Fourlanos S, Harrison LC (2010) Deconstructing the stereotypes of diabetes within the modern diabetogenic environment. Nature Rev Endocrinol  5: 483-89. PMID: 19636326 [PubMed - indexed for MEDLINE]
  8. Barrett JC et al (2009). Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes. Nat Genet 41: 703-707 PMID: 19430480 [PubMed - indexed for MEDLINE]
  9. Couper JJ, Beresford S, Hirte C, Baghurst P, Pollard A, Tait BD, Harrison LC, Colman PG (2009) Weight gain in early life predicts risk of islet autoimmunity in children with a first degree relative with type 1 diabetes. Diabetes Care 32: 94 - 99 PMID: 18835948 [PubMed - in process]
  10. Harrison LC (2009). Vaccination for autoimmune and other chronic inflammatory disorders. In: New Generation Vaccines, 4th edition (Levine MM, Ed). Informa Health Care, New York, NY pp969-981.

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Current Laboratory Members

Faculty Member: Len Harrison, DSc Melb FRACP MB BS NSW MD Melb FRCPA

Senior Postdoctoral Fellow: John Wentworth, MB BS Qld PhD Cantab

Postdoctoral Fellow: Maria Esther Bandala Sanchez, BSc(Hons) MSc PhD LaT

Postdoctoral Fellow: Yuxia Zhang, PhD IMCAS

Technical Consultant: Ralph Boehmer, PhD Hamburg

Research Assistant: Desiree Jeanne Butler, BSc(Hons) WA

Research Assistant: Julia Donald, BBiomedSci Melb

Research Assistant: Filipp Esselborn, BSc MSc Ruhr

Research Assistant: Gaetano Naselli, BSc Melb

Research Assistant: Alana Neale, BSc(Hons) Melb

Research Assistant: Natalie Stone, BAppSc RMIT

Postgraduate Student: Priscilla Auyeung,MB BS UQ, FRCPA, FRACP

Postgraduate Student: Julian Bosco, FRACP FRCPA MBBS BSc Med UNSW

Postgraduate Student: Maryam Rashidi,MD:Yazd Medical University

Postgraduate Student: Janet Yeo, BSc(Hons) Melb