• Levings, Megan

    Titles

    Investigator, BC Children's Hospital
    Professor, Department of Surgery, University of British Columbia

    Degrees / Designations
    PhD
    Primary Area of Research
    Childhood Diseases
    Secondary Area(s) of Research
    Phone
    604-875-2000 ext. 4686
    Fax
    604-875-2373
    Lab Phone
    Mailing Address

    BC Children's Hospital Research Institute
    Room A4-186
    950 West 28th Avenue
    Vancouver, BC V5Z 4H4

    Affiliate Websites
    Research Areas
    • T Regulatory Cells 
    • Peripheral Tolerance
    Summary

    Research in my laboratory is focused on a novel subset of CD4+ T cells, termed T regulatory (Treg) cells, which control immune homeostasis. Although we know that Treg cells have a fundamental role in regulating immunity to both self and foreign proteins, little is known about how they function. Current work is focused on determining how Treg cells differ from normal CD4+ T cells at both the biochemical and molecular levels, and elucidating their role in transplantation tolerance, cancer and inflammatory bowel disease. A long-term goal is to develop methods to generate Treg cells in vitro for use as a cellular therapy to replace standard immunosuppression in the context of organ transplantation or to restore tolerance in the context of autoimmunity.

    Current Projects
    Specific projects currently on-going include:  
    • Studying the unique cell-signalling pathways in human and mouse Tregs 
    • Developing biomarkers to track the function of Tregs 
    • Studying the interaction between Tregs and IL-17-producing cells 
    • Studying tissue-derived Tregs from patients with graft versus host disease or inflammatory bowel disease 
    • Developing methods to use Tregs as a cellular therapy in transplantation 
    • Developing biomarkers to predict responses to therapy in inflammatory bowel disease
    Selected Publications

    Insulin Inhibits IL-10–Mediated Regulatory T Cell Function: Implications for Obesity. Jonathan M. Han, Scott J. Patterson, Madeleine Speck, Jan A. Ehses and Megan K. Levings. J Immunol. 2014 Jan 15;192(2):623-9. doi: 10.4049/jimmunol.1302181. Epub 2013 Dec 9.. PMID: 24323581

    Helios+ and Helios- cells coexist within the natural FOXP3+ T regulatory cell subset in humans. Himmel ME, MacDonald KG, Garcia RV, Steiner TS, Levings MK. J Immunol. 2013 Mar 1;190(5):2001-8. PMID: 23359504

    A novel function for FOXP3 in humans: intrinsic regulation of conventional T cells. McMurchy AN, Gillies J, Gizzi MC, Riba M, Garcia-Manteiga JM, Cittaro D, Lazarevic D, Di Nunzio S, Piras IS, Bulfone A, Roncarolo MG, Stupka E, Bacchetta R, Levings MK. Blood. 2013 Feb 21;121(8):1265-75. PMID: 23169781

    Moving to tolerance: Clinical application of T regulatory cells. McMurchy AN, Bushell A, Levings MK, Wood KJ. Semin Immunol. 2011 May 28. PMID: 2160722

    Cutting edge: PHLPP regulates the development, function, and molecular signaling pathways of regulatory T cells. Patterson SJ, Han JM, Garcia R, Assi K, Gao T, O'Neill A, Newton AC, Levings MK. J Immunol. 2011 May 15;186(10):5533-7. PMID: 21498666

    Environmental influences on T regulatory cells in inflammatory bowel disease. Hardenberg G, Steiner TS, Levings MK. Semin Immunol. 2011 Apr;23(2):130-8. Review. PMID: 21295492

    Human CD4+ FOXP3+ regulatory T cells produce CXCL8 and recruit neutrophils. Himmel ME, Crome SQ, Ivison S, Piccirillo C, Steiner TS, Levings MK. Eur J Immunol. 2011 Feb;41(2):306-12. PMID: 21268001

    Adenoviral-transduced dendritic cells are susceptible to suppression by T regulatory cells and promote interleukin 17 production. Wang AY, Crome SQ, Jenkins KM, Medin JA, Bramson JL, Levings MK. Cancer Immunol Immunother. 2011 Mar; 60 (3):381-8. PMID: 21153637

    Point mutants of forkhead box P3 that cause immune dysregulation, polyendocrinopathy, enteropathy, X-linked have diverse abilities to reprogram T cells into regulatory T cells. McMurchy AN, Gillies J, Allan SE, Passerini L, Gambineri E, Roncarolo MG, Bacchetta R, Levings MK. J Allergy Clin Immunol. 2010 Dec;126(6):1242-51. PMID: 21036387

    Cutaneous GVHD is associated with the expansion of tissue-localized Th1 and not Th17 cells. Broady R, Yu J, Chow V, Tantiworawit A, Kang C, Berg K, Martinka M, Ghoreishi M, Dutz J, Levings MK. Blood. 2010 Dec 16;116(25): 5748-51. PMID: 20864580

    Inflammatory effects of ex vivo human Th17 cells are suppressed by regulatory T cells. Crome SQ, Clive B, Wang AY, Kang CY, Chow V, Yu J, Lai A, Ghahary A, Broady R, Levings MK. J Immunol. 2010 Sep 15;185(6):3199-208. PMID: 20720207

    Function and regulation of human Th17 cells in health and disease. Crome, S.Q., Wang, A.Y. and Levings, M.K.Clinical and Experimental Immunology, 2010, 159:109-119. PMID: 19912252

    ATG-induced expression of FOXP3 in human CD4+ T cells in vitro is associated with T cell activation and not the induction of FOXP3+ T regulatory cells. Broady R, Yu J, and Levings MK.Blood, 2009. PMID: 19822903

    SHIP regulates the reciprocal development of T regulatory and Th17 cells. Locke, N.R., Patterson, S, Hamilton, M, Sly. L.M., Krystal, G., and Levings, M.K. J. IMMUNOLOGY. 2009, 183:975-983. PMID: 19542365

    Grants

    Genome Canada and CIHR: Applied Research Project Competition in Genomics and Personalized Health (2013)

    CIHR and Genome BC: Canadian National Transplant Research Program (2013)

    Canadian Cancer Society Research Institute: "Generation of antigen specific T regulatory cells to treat GVHD post allogeneic stem cell transplant" (2013)

    Genome Canada: IBD Genomic Medicine Consortium (iGenoMed) (2013)

    CIHR Team Grant: The Canadian National Transplant Research Project (2013)

    CIHR Operating Grant – Project: "The role of FOXP3 and IL-1-family cytokines in regulating CD4+ T cell subsets in healthy humans, and in patients with chronic skin inflammation" (2013)

    Child & Family Research Institute - Project: "Gene Signatures of T regulatory cells as a molecular biomarker in type 1 diabetes" (2012)

    Eli and Edythe Broad Foundation: Broad Medical Research Program for Inflammatory Bowel Disease (IBD) Grant. Project "Flagellin-specific T cells in Crohn's disease" (2011)

    Crohn's and Colitis Foundation of Canada: Innovation in IBD research (2011)

    Child & Family Research Institute: Establishment Award (2010)

    Genome BC: Creation of a high throughput gene expression screening platform for T regulatory cells (2010)

    UBC Faculty of Medicine: The Impact of regulatory T cells on graft versus leukemia responses (2010)

    Canadian Institute of Health Research: Molecular and cellular biology of human Th17 cells in health and disease (2009)

    Leukemia Lymphoma Society: Study and manipulation of T regulatory cells in the periphery and tissues of patients with cGVHD (2008)

    Canadian Institute of Health Research: Manipulating regulatory T cells to control inflammatory skin diseases (2008)

    Cancer Research Society: Regulatory T cell therapy for graft versus host disease (2007)

    Canadian Institute of Health Research: Molecular and cellular biology of Regulatory cells (2007)

    Roche Organ Transplantation Research Foundation: manipulating FOXP3 to induce transplantation to tolerance in humans (2007)

    Canadian Institute of Health Research: Immune-modulation of Regulatory Mechanisms in Mucosal Immunity: A multi-disciplinary bench-to-bedside approach to the study and treatment of IBD (2007)

    Canadian Institute of Health Research: Human T regulatory cells: molecular dissection of their ontogeny and functions (2007)

    Honours & Awards

    2003-2013 CRC in Transplantation Tier II; Canada Research Chairs

    2012 Genome Canada-CIHR Competition in Personalized Health

    2009 Canadian Society for Immunology; New Investigator Award

    2007 Richard J. Finley Research Scholar Award; University of British Columbia

    2003-2007 Career Investigator Scholar Award; Michael Smith Foundation for Health Research

    2004 Hjalmar W. Johnson New Investigator Award; University of British Columbia

    2003 New Investigator Award; Canadian Institutes of Health Research

    Research Group Members
    • Lab manager: Rosa Garcia
    • Technicians: Jana Gillies, Jessica Huang
    • Graduate Students: Kate MacDonald, Jonathan Han, Maggie Yu, Jens Vent-Schmidt
    • Post-doctoral fellows: Scott Patterson
    • Clinician Scientist: Raewyn Broady