Overview

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.

Publications

Guiding regulatory T cells to the allograft
Current Opinion in Organ Transplantation
Caroline Lamarche, Megan K. Levings
DOI: 10.1097/mot.0000000000000483
11/2017

Engineered Tolerance: Tailoring Development, Function, and Antigen-Specificity of Regulatory T Cells
Frontiers in Immunology
Nicholas A. J. Dawson, Jens Vent-Schmidt, Megan K. Levings
DOI: 10.3389/fimmu.2017.01460
11/2017

Harnessing Advances in T Regulatory Cell Biology for Cellular Therapy in Transplantation
Transplantation
Avery J. Lam, Romy E. Hoeppli, Megan K. Levings
DOI: 10.1097/tp.0000000000001757
10/2017

The outstanding questions in transplantation: It's about time…
American Journal of Transplantation
Jamil Azzi, Giorgio Raimondi, Valeria Mas, Leonardo V. Riella, Nissreen Elfadawy, Kassem Safa, David Wojciechowski, Mazhar Kanak, Rajat Nog, Jonathan S. Maltzman, Mandy L. Ford, Jordan S. Pober, Xung-Rong Luo, David Rothstein, Michelle L. Miller, David Matthews, William Burlingham, Megan Levings, Peter Heeger, Lauren Higdon, John Gill, Ronald G. Gill, Maria-Luisa Alegre
DOI: 10.1111/ajt.14450
09/2017

Adipose-tissue regulatory T cells: Critical players in adipose-immune crosstalk
European Journal of Immunology
Maike Becker, Megan K. Levings, Carolin Daniel
DOI: 10.1002/eji.201646739
09/2017

OR42 Expanded thymic regulatory T cells (Tregs) have low class I HLA expression levels and are HLA-DR negative – Potential for ‘Off-The-Shelf’ Cellular Therapy?
Human Immunology
Esme Dijke, Romy Hoeppli, Ingrid Larsen, Ivan Rebeyka, David Ross, Megan Levings, Lori West
DOI: 10.1016/j.humimm.2017.06.048
09/2017

Antigen-specific regulatory T cells: are police CARs the answer?
Translational Research
Nicholas A.J. Dawson, Megan K. Levings
DOI: 10.1016/j.trsl.2017.06.009
09/2017

Thymic progenitors of TCRaß + CD8aa intestinal intraepithelial lymphocytes require RasGRP1 for development
The Journal of Experimental Medicine
Dominic P. Golec, Romy E. Hoeppli, Laura M. Henao Caviedes, Jillian McCann, Megan K. Levings, Troy A. Baldwin
DOI: 10.1084/jem.20170844
06/2017

Regulatory T-cells drive immune dysfunction in CLL
Leukemia & Lymphoma
Deepesh Lad, Romy Hoeppli, Qing Huang, Rosa Garcia, Lixin Xu, Cynthia Toze, Raewyn Broady, Megan Levings
DOI: 10.1080/10428194.2017.1330475
06/2017

Development of GMP-Compatible Protocols for Thymus-Derived Regulatory T Cell Expansion
Transplantation
Katherine MacDonald, Romy Hoeppli, James Piret, Esmé Dijke, Lori West, Megan Levings
DOI: 10.1097/01.tp.0000520303.10595.5e
05/2017

Migration Capacity of Thymic Regulatory T Cells can be Tuned by Expansion in Cytokine-Enriched Culture Conditions
Transplantation
Romy E. Hoeppli, Esmé Dijke, Andrew Campbell, Lori J. West, Megan K. Levings
DOI: 10.1097/01.tp.0000520352.47820.13
05/2017

Standardized Immunophenotyping in the Canadian National Transplant Research Program pilot trial of post HSCT samples and development of automated gating pipelines
Transplantation
Sabine Ivison, Salima Janmohamed, Mehrnoush Malek, Rosa Garcia, Raewyn Broady, Anne Halpin, Manon Richaud, Rollin Brant, Jean-Sebastien Delisle, Lori West, Ryan R. Brinkman, Megan Levings
DOI: 10.1097/01.tp.0000520396.84839.9b
05/2017

Thymus-Derived Treg Infusion to Prevent Graft Rejection in Heart-Transplanted Children Initial Exploration of a New Therapeutic Arsenal to Boost Immune Tolerance
Transplantation
Esther Bernaldo de Quirós, Verónica A. Pérez, Maribel Clemente, Juan Miguel Gil-Jaurena, María Teresa González, Marjorie Pion, Giovanna Lombardi, Lori J. West, Megan Levings, Rafael Correa-Rocha
DOI: 10.1097/01.tp.0000520350.40197.6b
05/2017

A Novel Whole Blood Assay Detects Flagellin-Specific CD4 + T Cells in Patients with Inflammatory Bowel Disease
Gastroenterology
Laura Cook, May Q. Wong, Rosa Garcia, Megan E. Himmel, Brian Bressler, Ernest G. Seidman, Theodore S. Steiner, Megan K. Levings
DOI: 10.1016/s0016-5085(17)32185-6
04/2017

Evaluating the Role of Tregs in the Progression of Multiple Myeloma
Clinical Lymphoma Myeloma and Leukemia
Deeepesh Lad, Raewyn Broady, Jessica Huang, Romy Hoeppli, Anne Pesenacker, Rosa Garcia, Lixin Xu, Megan Levings, Kevin Song
DOI: 10.1016/j.clml.2017.03.075
02/2017

Effect of Ex Vivo–Expanded Recipient Regulatory T Cells on Hematopoietic Chimerism and Kidney Allograft Tolerance Across MHC Barriers in Cynomolgus Macaques
Transplantation
Raimon Duran-Struuck, Hugo P. Sondermeijer, Leo Bühler, Paula Alonso-Guallart, Jonah Zitsman, Yojiro Kato, Anette Wu, Alicia N. McMurchy, David Woodland, Adam Griesemer, Mercedes Martinez, Svetlan Boskovic, Tatsuo Kawai, A. Benedict Cosimi, Cheng-Shie Wuu, Andrea Slate, Markus Y. Mapara, Sam Baker, Rafal Tokarz, Vivette D'Agati, Scott Hammer, Marcus Pereira, W. Ian Lipkin, Thomas Wekerle, Megan K. Levings, Megan Sykes
DOI: 10.1097/tp.0000000000001559
02/2017

Biomarker-guided stratification of autoimmune patients for biologic therapy
Current Opinion in Immunology
Sabine Ivison, Christine Des Rosiers, Sylvie Lesage, John D Rioux, Megan K Levings
DOI: 10.1016/j.coi.2017.09.006
2017

CD4+ T Cells Specific for C. difficile Toxins are a Marker of Patients with Active Relapsing Disease
Open Forum Infectious Diseases
Laura Cook, May Wong, William Rees, Torey Lau, Megan Levings, Theodore Steiner
DOI: 10.1093/ofid/ofx163.948
2017

Circulating gluten-specific FOXP3 + CD39 + regulatory T cells have impaired suppressive function in patients with celiac disease
Journal of Allergy and Clinical Immunology
Laura Cook, C. Mee Ling Munier, Nabila Seddiki, David van Bockel, Noé Ontiveros, Melinda Y. Hardy, Jana K. Gillies, Megan K. Levings, Hugh H. Reid, Jan Petersen, Jamie Rossjohn, Robert P. Anderson, John J. Zaunders, Jason A. Tye-Din, Anthony D. Kelleher
DOI: 10.1016/j.jaci.2017.02.015
2017

Filgrastim-Stimulated Bone Marrow Compared with Filgrastim-Mobilized Peripheral Blood in Myeloablative Sibling Allografting for Patients with Hematologic Malignancies: A Randomized Canadian Blood and Marrow Transplant Group Study
Biology of Blood and Marrow Transplantation
Stephen Couban, Mahmoud Aljurf, Sylvie Lachance, Irwin Walker, Cynthia Toze, Morel Rubinger, Jeffrey H. Lipton, Stephanie J. Lee, Jeff Szer, Richard Doocey, Ian D. Lewis, Lothar Huebsch, Kang Howson-Jan, Michel Lalancette, Fahad Almohareb, Nadeem Chaudhri, Sabine Ivison, Raewyn Broady, Megan Levings, Diane Fairclough, Gerald Devins, David Szwajcer, Ronan Foley, Clayton Smith, Tony Panzarella, Holly Kerr, Amina Kariminia, Kirk R. Schultz
DOI: 10.1016/j.bbmt.2016.04.017
08/2016

How antigen specificity directs regulatory T-cell function: self, foreign and engineered specificityHow antigen specificity directs Treg function
HLA
R. E. Hoeppli, K. G. MacDonald, M. K. Levings, L. Cook
DOI: 10.1111/tan.12822
06/2016

Alloantigen-specific regulatory T cells generated with a chimeric antigen receptor
Journal of Clinical Investigation
Katherine G. MacDonald, Romy E. Hoeppli, Qing Huang, Jana Gillies, Dan S. Luciani, Paul C. Orban, Raewyn Broady, Megan K. Levings
DOI: 10.1172/jci82771
03/2016

T regulatory cell chemokine production mediates pathogenic T cell attraction and suppression
Journal of Clinical Investigation
Scott J. Patterson, Anne M. Pesenacker, Adele Y. Wang, Jana Gillies, Majid Mojibian, Kim Morishita, Rusung Tan, Timothy J. Kieffer, C. Bruce Verchere, Constadina Panagiotopoulos, Megan K. Levings
DOI: 10.1172/jci83987
02/2016

A Regulatory T-Cell Gene Signature Is a Specific and Sensitive Biomarker to Identify Children With New-Onset Type 1 Diabetes
Diabetes
Anne M. Pesenacker, Adele Y. Wang, Amrit Singh, Jana Gillies, Youngwoong Kim, Ciriaco A. Piccirillo, Duc Nguyen, W. Nicholas Haining, Scott J. Tebbutt, Constadina Panagiotopoulos, Megan K. Levings
DOI: 10.2337/db15-0572
01/2016

Obesity-Associated Adipose Tissue Inflammation and TransplantationObesity, Adipose Tissue, and Transplantation
American Journal of Transplantation
D. Wu, N. A. J. Dawson, M. K. Levings
DOI: 10.1111/ajt.13578
01/2016

The role of FOXP3 in autoimmunity
Current Opinion in Immunology
Anne M Pesenacker, Laura Cook, Megan K Levings
DOI: 10.1016/j.coi.2016.07.004
2016

CCL22 Prevents Rejection of Mouse Islet Allografts and Induces Donor-Specific Tolerance
Cell Transplantation
Joel Montane, Merce Obach, Sigrid Alvarez, Loraine Bischoff, Derek L. Dai, Galina Soukhatcheva, John J. Priatel, Gijs Hardenberg, Megan K. Levings, Rusung Tan, Paul C. Orban, C. Bruce Verchere
DOI: 10.3727/096368914x685249
10/2015

Discarded Human Thymus Is a Novel Source of Stable and Long-Lived Therapeutic Regulatory T CellsTherapeutic Tregs From Discarded Human Thymus
American Journal of Transplantation
I. E. Dijke, R. E. Hoeppli, T. Ellis, J. Pearcey, Q. Huang, A. N. McMurchy, K. Boer, A. M. A. Peeters, G. Aubert, I. Larsen, D. B. Ross, I. Rebeyka, A. Campbell, C. C. Baan, M. K. Levings, L. J. West
DOI: 10.1111/ajt.13456
09/2015

Tr1 Cells, but Not Foxp3+Regulatory T Cells, Suppress NLRP3 Inflammasome Activation via an IL-10–Dependent Mechanism
The Journal of Immunology
Yu Yao, Jens Vent-Schmidt, Matthew D. McGeough, May Wong, Hal M. Hoffman, Theodore S. Steiner, Megan K. Levings
DOI: 10.4049/jimmunol.1403225
06/2015

Regulatory T cells produce profibrotic cytokines in the skin of patients with systemic sclerosis
Journal of Allergy and Clinical Immunology
Katherine G. MacDonald, Nicholas A.J. Dawson, Qing Huang, James V. Dunne, Megan K. Levings, Raewyn Broady
DOI: 10.1016/j.jaci.2014.12.1932
04/2015

IL-33 Reverses an Obesity-Induced Deficit in Visceral Adipose Tissue ST2+T Regulatory Cells and Ameliorates Adipose Tissue Inflammation and Insulin Resistance
The Journal of Immunology
Jonathan M. Han, Dan Wu, Heather C. Denroche, Yu Yao, C. Bruce Verchere, Megan K. Levings
DOI: 10.4049/jimmunol.1500020
04/2015

Phenotype, Function and Expansion of Regulatory T Cells in the Cynomolgus Macaque (Macaca fascicularis)
Biology of Blood and Marrow Transplantation
Paula Alonso Guallart, Jonah Zitsman, Hugo Sondermeijer, Leo Bühler, Christopher Ovanez, Alicia McMurchy, Megan Levings, Megan Sykes, Raimon Duran-Struuck
DOI: 10.1016/j.bbmt.2014.11.445
02/2015

Induction of Durable Mixed Hematopoietic Chimerism and Immune Tolerance in Monkeys
Biology of Blood and Marrow Transplantation
Paula Alonso Guallart, Jonah Zitsman, Hugo Sondermeijer, David Woodland, Yojiro Kato, Joshua Weiner, Adam Griesemer, Leo Bühler, Alicia McMurchy, Megan Levings, Megan Sykes, Raimon Duran-Struuck
DOI: 10.1016/j.bbmt.2014.11.040
02/2015

The Environment of Regulatory T Cell Biology: Cytokines, Metabolites, and the Microbiome
Frontiers in Immunology
Romy E. Hoeppli, Dan Wu, Laura Cook, Megan K. Levings
DOI: 10.3389/fimmu.2015.00061
02/2015

Restimulation After Cryopreservation and Thawing Preserves the Phenotype and Function of Expanded Baboon Regulatory T Cells
Transplantation Direct
Joshua Weiner, Raimon Duran-Struuck, Jonah Zitsman, Leo Buhler, Hugo Sondermeijer, Alicia N. McMurchy, Megan K. Levings, Megan Sykes, Adam Griesemer
DOI: 10.1097/txd.0000000000000511
02/2015

Methyltransferase G9A regulates T cell differentiation during murine intestinal inflammation
Journal of Clinical Investigation
Frann Antignano, Kyle Burrows, Michael R. Hughes, Jonathan M. Han, Ken J. Kron, Nadia M. Penrod, Menno J. Oudhoff, Steven Kai Hao Wang, Paul H. Min, Matthew J. Gold, Alistair L. Chenery, Mitchell J.S. Braam, Thomas C. Fung, Fabio M.V. Rossi, Kelly M. McNagny, Cheryl H. Arrowsmith, Mathieu Lupien, Megan K. Levings, Colby Zaph
DOI: 10.1172/jci69592
03/2014

Control of tissue-localized immune responses by human regulatory T cellsHighlights
European Journal of Immunology
Anne M. Pesenacker, Raewyn Broady, Megan K. Levings
DOI: 10.1002/eji.201344205
2014

The Role of FOXP3 in Regulating Immune Responses
International Reviews of Immunology
Jens Vent-Schmidt, Jonathan M. Han, Katherine G. MacDonald, Megan K. Levings
DOI: 10.3109/08830185.2013.811657
08/2013

Immune Regulation in Obesity-Associated Adipose Inflammation
The Journal of Immunology
J. M. Han, M. K. Levings
DOI: 10.4049/jimmunol.1301035
07/2013

Response to Comment on "Helios+ and Helios- Cells Coexist within the Natural FOXP3+ T Regulatory Cell Subset in Humans"
The Journal of Immunology
K. G. MacDonald, J. M. Han, M. E. Himmel, Q. Huang, B. Kan, A. I. M. Campbell, P. M. Lavoie, M. K. Levings
DOI: 10.4049/jimmunol.1390019
04/2013

Autologous transplant for autoimmune disease: optimizing the regulatory T cells
Cytotherapy
T.D. Prestidge, J.H. Davis, J. Huang, M. Himmel, M. Levings
DOI: 10.1016/j.jcyt.2013.01.161
04/2013

Pediatric thymic tissue as a source of CD25+FOXP3+ regulatory T cells (Tregs) for cellular therapy
Cytotherapy
E. Dijke, M. Levings, A. McMurchy, I. Larsen, I. Rebeyka, D. Ross, L. West
DOI: 10.1016/j.jcyt.2013.01.160
04/2013

Helios+ and Helios- Cells Coexist within the Natural FOXP3+ T Regulatory Cell Subset in Humans
The Journal of Immunology
M. E. Himmel, K. G. MacDonald, R. V. Garcia, T. S. Steiner, M. K. Levings
DOI: 10.4049/jimmunol.1201379
01/2013

Th-2 cytokine producing Tregs in the skin of patients with systemic sclerosis
Frontiers in Immunology
Broady Raewyn, Huang Qing, MacDonald Katherine, Dunne James, Levings Megan
DOI: 10.3389/conf.fimmu.2013.02.01011
2013

Insulin impairs regulatory T cell function: implications for obesity
Frontiers in Immunology
Han Jonathan, Patterson Scott, Ehses Jan, Levings Megan
DOI: 10.3389/conf.fimmu.2013.02.00587
2013

Expansion of Highly Suppressive FOXP3+ Regulatory T Cells from Pediatric Thymic Tissue2239
Transplantation Journal
E. Dijke, A. McMurchy, M. Levings, I. Larsen, I. Rebeyka, D. Ross, L. West
DOI: 10.1097/00007890-201211271-02368
11/2012

A novel function for FOXP3 in humans: intrinsic regulation of conventional T cells
Blood
A. N. McMurchy, J. Gillies, M. C. Gizzi, M. Riba, J. M. Garcia-Manteiga, D. Cittaro, D. Lazarevic, S. Di Nunzio, I. S. Piras, A. Bulfone, M. G. Roncarolo, E. Stupka, R. Bacchetta, M. K. Levings
DOI: 10.1182/blood-2012-05-431023
11/2012

In Vitro Generation of Human T Regulatory Cells: Generation, Culture, and Analysis of FOXP3-Transduced T Cells
Basic Cell Culture Protocols
Alicia N. McMurchy, Megan K. Levings
DOI: 10.1007/978-1-62703-128-8_8
10/2012

Chemokine Induced Tolerance in Mouse Islet Allografts
Canadian Journal of Diabetes
Joel Montane, Merce Obach, Loraine Bischoff, Galina Soukhatcheva, Paul C. Orban, Gijs Hardenberg, Megan K. Levings, Rusung Tan, C. Bruce Verchere
DOI: 10.1016/j.jcjd.2012.07.468
10/2012

ATP conditions intestinal epithelial cells to an inflammatory state that promotes components of DC maturationImmunodulation
European Journal of Immunology
Yu Yao, Megan K. Levings, Theodore S. Steiner
DOI: 10.1002/eji.201142213
10/2012

Active vitamin D (1,25-dihydroxyvitamin D3) increases host susceptibility to Citrobacter rodentium by suppressing mucosal Th17 responses
AJP: Gastrointestinal and Liver Physiology
N. R. Ryz, S. J. Patterson, Y. Zhang, C. Ma, T. Huang, G. Bhinder, X. Wu, J. Chan, A. Glesby, H. P. Sham, J. P. Dutz, M. K. Levings, K. Jacobson, B. A. Vallance
DOI: 10.1152/ajpgi.00320.2012
09/2012

T regulatory cell therapy in transplantationstability, localization and functional specialization
Current Opinion in Organ Transplantation
Katherine G. MacDonald, Paul C. Orban, Megan K. Levings
DOI: 10.1097/mot.0b013e328355aaaf
08/2012

Regulatory T-cell therapy for inflammatory bowel disease: more questions than answersTreg therapy in inflammatory bowel disease
Immunology
Megan E. Himmel, Yu Yao, Paul C. Orban, Theodore S. Steiner, Megan K. Levings
DOI: 10.1111/j.1365-2567.2012.03572.x
04/2012

Inflammation-Driven Reprogramming of CD4+Foxp3+ Regulatory T Cells into Pathogenic Th1/Th17 T Effectors Is Abrogated by mTOR Inhibition in vivo
PLoS ONE
Ekaterina Yurchenko, Marina T. Shio, Tony C. Huang, Maria Da Silva Martins, Moshe Szyf, Megan K. Levings, Martin Olivier, Ciriaco A. Piccirillo
DOI: 10.1371/journal.pone.0035572
04/2012

Toll-like receptor 5 deficiency protects from wasting disease in a T cell transfer colitis model in T cell receptor-ß-deficient mice
Inflammatory Bowel Diseases
Gijs Hardenberg, Yu Yao, Ciriaco A. Piccirillo, Megan K. Levings, Theodore S. Steiner
DOI: 10.1002/ibd.21738
01/2012

The Role of the PI3K Signaling Pathway in CD4+ T Cell Differentiation and Function
Frontiers in Immunology
Jonathan M. Han, Scott J. Patterson, Megan K. Levings
DOI: 10.3389/fimmu.2012.00245
2012

Transcriptome Analysis Reveals Markers of Aberrantly Activated Innate Immunity in Vitiligo Lesional and Non-Lesional Skin
PLoS ONE
Richard Yu, Raewyn Broady, Yuanshen Huang, Yang Wang, Jie Yu, Min Gao, Megan Levings, Shencai Wei, Shengquan Zhang, Aie Xu, Mingwan Su, Jan Dutz, Xuejun Zhang, Youwen Zhou
DOI: 10.1371/journal.pone.0051040
2012

TH17 Cells in Autoimmunity and Immunodeficiency: Protective or Pathogenic?
Frontiers in Immunology
Ashish K. Marwaha, Nicole J. Leung, Alicia N. McMurchy, Megan K. Levings
DOI: 10.3389/fimmu.2012.00129
2012

Human Th1 and Th17 Cells Exhibit Epigenetic Stability at Signature Cytokine and Transcription Factor Loci
The Journal of Immunology
C. J. Cohen, S. Q. Crome, K. G. MacDonald, E. L. Dai, D. L. Mager, M. K. Levings
DOI: 10.4049/jimmunol.1101058
11/2011

CD4+Foxp3+ regulatory T cells suppress ¿d T-cell effector functions in a model of T-cell-induced mucosal inflammation
European Journal of Immunology
Ekaterina Yurchenko, Megan K. Levings, Ciriaco A. Piccirillo
DOI: 10.1002/eji.201141814
11/2011

Cellular magnetic resonance imaging of monocyte-derived dendritic cell migration from healthy donors and cancer patients as assessed in a scid mouse model
Cytotherapy
Xizhong Zhang, Sonali N. de Chickera, Christy Willert, Vasliki Economopoulos, Jennifer Noad, Roja Rohani, Adele Y. Wang, Megan K. Levings, Elizabeth Scheid, Ronan Foley, Paula J. Foster, Gregory A. Dekaban
DOI: 10.3109/14653249.2011.605349
11/2011

Moving to tolerance: Clinical application of T regulatory cells
Seminars in Immunology
Alicia N. McMurchy, Andrew Bushell, Megan K. Levings, Kathryn J. Wood
DOI: 10.1016/j.smim.2011.04.001
08/2011

Prevention of murine autoimmune diabetes by CCL22-mediated Treg recruitment to the pancreatic islets
Journal of Clinical Investigation
Joel Montane, Loraine Bischoff, Galina Soukhatcheva, Derek L. Dai, Gijs Hardenberg, Megan K. Levings, Paul C. Orban, Timothy J. Kieffer, Rusung Tan, C. Bruce Verchere
DOI: 10.1172/jci43048
08/2011

SHIP-Deficient Dendritic Cells, Unlike Wild Type Dendritic Cells, Suppress T Cell Proliferation via a Nitric Oxide-Independent Mechanism
PLoS ONE
Frann Antignano, Melisa Hamilton, Scott Patterson, Victor Ho, Carla Cohen, Megan K. Levings, Gerald Krystal
DOI: 10.1371/journal.pone.0021893
07/2011

Environmental influences on T regulatory cells in inflammatory bowel disease
Seminars in Immunology
Gijs Hardenberg, Theodore S. Steiner, Megan K. Levings
DOI: 10.1016/j.smim.2011.01.012
04/2011

Human CD4+FOXP3+ regulatory T cells produce CXCL8 and recruit neutrophils
European Journal of Immunology
Megan E. Himmel, Sarah Q. Crome, Sabine Ivison, Ciriaco Piccirillo, Theodore S. Steiner, Megan K. Levings
DOI: 10.1002/eji.201040459
01/2011

The Stress signal extracellular ATP modulates antiflagellin immune responses in intestinal epithelial cells
Inflammatory Bowel Diseases
Sabine M. Ivison, Megan E. Himmel, Matt Mayer, Yu Yao, Arnawaz Kifayet, Megan K. Levings, Theodore S. Steiner
DOI: 10.1002/ibd.21428
01/2011

Role of epithelial integrin-linked kinase in promoting intestinal inflammation: effects on CCL2, fibronectin and the T cell repertoire
BMC Immunology
Kiran Assi, Scott Patterson, Shoukat Dedhar, David Owen, Megan Levings, Baljinder Salh
DOI: 10.1186/1471-2172-12-42
2011

Suppression assays with human T regulatory cells: A technical guideHighlights
European Journal of Immunology
Alicia N. McMurchy, Megan K. Levings
DOI: 10.1002/eji.201141651
2011

T Regulatory Cells and Cancer Immunotherapy
Experimental and Applied Immunotherapy
Adele Y. Wang and Megan K. Levings
DOI: 10.1007/978-1-60761-980-2_10
11/2010

Natural killer T cells constitutively expressing the interleukin-2 receptor a chain early in life are primed to respond to lower antigenic stimulationCD25 expression primes neonatal iNKT cells
Immunology
Mihoko Ladd, Ashish Sharma, Qing Huang, Adele Y. Wang, Lixin Xu, Indira Genowati, Megan K. Levings, Pascal M. Lavoie
DOI: 10.1111/j.1365-2567.2010.03304.x
09/2010

Leishmania Exosomes Modulate Innate and Adaptive Immune Responses through Effects on Monocytes and Dendritic Cells
The Journal of Immunology
J. M. Silverman, J. Clos, E. Horakova, A. Y. Wang, M. Wiesgigl, I. Kelly, M. A. Lynn, W. R. McMaster, L. J. Foster, M. K. Levings, N. E. Reiner
DOI: 10.4049/jimmunol.1000541
09/2010

Deconvolution and chromatic aberration corrections in quantifying colocalization of a transcription factor in three-dimensional cellular space
Micron
Thomas Abraham, Sarah E. Allan, Megan K. Levings
DOI: 10.1016/j.micron.2010.03.005
08/2010

Inflammatory Effects of Ex Vivo Human Th17 Cells Are Suppressed by Regulatory T Cells
The Journal of Immunology
S. Q. Crome, B. Clive, A. Y. Wang, C. Y. Kang, V. Chow, J. Yu, A. Lai, A. Ghahary, R. Broady, M. K. Levings
DOI: 10.4049/jimmunol.1000557
08/2010

CD161 is a marker of all human IL-17-producing T-cell subsets and is induced by RORC
European Journal of Immunology
Laura Maggi, Veronica Santarlasci, Manuela Capone, Anna Peired, Francesca Frosali, Sarah Q. Crome, Valentina Querci, Massimiliano Fambrini, Francesco Liotta, Megan K. Levings, Enrico Maggi, Lorenzo Cosmi, Sergio Romagnani, Francesco Annunziato
DOI: 10.1002/eji.200940257
05/2010

TLR5 is not required for flagellin-mediated exacerbation of DSS colitis
Inflammatory Bowel Diseases
Sabine M. Ivison, Megan E. Himmel, Gijs Hardenberg, Paige A.J. Wark, Arnawaz Kifayet, Megan K. Levings, Theodore S. Steiner
DOI: 10.1002/ibd.21097
03/2010

Constitutive Expression of CD25 on the Surface of Neonatal (invariant) Natural Killer T Cells Primes Them to Proliferate with Lower Antigenic Stimulation
Clinical Immunology
Ashish Sharma, Mihoko Whalen, Qing Huang, Adele Wang, Lixin Xu, Indira Genowati, Meghan Levings, Pascal Lavoie
DOI: 10.1016/j.clim.2010.03.151
01/2010

PHLPP Regulates the Development, Function and Molecular Signaling Pathways of T Regulatory Cells
Clinical Immunology
Scott Patterson, Rosa Garcia, Audrey O'Neill, Tianyan Gao, Alexandra Newton, Megan Levings
DOI: 10.1016/j.clim.2010.03.025
01/2010

Increased Fraction of IL-17 Secreting Cells in Type 1 Diabetes
Clinical Immunology
Ashish Marwaha, Megan Levings, Sarah Crome, Constadina Panagiotopoulos, John Priatel, Rusung Tan
DOI: 10.1016/j.clim.2010.03.398
01/2010

The Inflammatory Effects of ex vivo Human T Helper 17 Cells are Suppressed by T Regulatory Cells
Clinical Immunology
Sarah Crome, Breanna Clive, Adele Wang, Christine Kang, Vickie Chow, Jessie Yiu, Raewyn Broady, Megan Levings
DOI: 10.1016/j.clim.2010.03.361
01/2010

Adenoviral-transduced dendritic cells are susceptible to suppression by T regulatory cells and promote interleukin 17 production
Cancer Immunology, Immunotherapy
Adele Y. Wang, Sarah Q. Crome, Kristina M. Jenkins, Jeffrey A. Medin, Jonathan L. Bramson, Megan K. Levings
DOI: 10.1007/s00262-010-0948-4
2010

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
Journal of Allergy and Clinical Immunology
Alicia N. McMurchy, Jana Gillies, Sarah E. Allan, Laura Passerini, Eleonora Gambineri, Maria Grazia Roncarolo, Rosa Bacchetta, Megan K. Levings
DOI: 10.1016/j.jaci.2010.09.001
2010

The role of retinoic acid‐related orphan receptor variant 2 and IL‐17 in the development and function of human CD4+T cells
European Journal of Immunology
Sarah Q. Crome, Adele Y. Wang, Christine Y. Kang, Megan K. Levings
DOI: 10.1002/eji.200838908
06/2009

SHIP Regulates the Reciprocal Development of T Regulatory and Th17 Cells
The Journal of Immunology
N. R. Locke, S. J. Patterson, M. J. Hamilton, L. M. Sly, G. Krystal, M. K. Levings
DOI: 10.4049/jimmunol.0803749
06/2009

Quantifying colocalization of a conditionally active transcription factor FOXP3 in three-dimensional cellular space
Three-Dimensional and Multidimensional Microscopy: Image Acquisition and Processing XVI
Thomas Abraham, Sarah E. Allan, Megan K. Levings
DOI: 10.1117/12.808049
02/2009

Molecular Regulation ofCellular Immunity by FOXP3
Forkhead Transcription Factors
Alicia N. McMurchy and Sara Di Nunzio and Maria Grazia Roncarolo and Rosa Bacchetta and Megan K. Levings
DOI: 10.1007/978-1-4419-1599-3_3
2009

Graft versus host disease: suppression by statins
Nature Medicine
Raewyn Broady, Megan K Levings
DOI: 10.1038/nm1108-1155
11/2008

Inducible reprogramming of human T cells into Treg cells by a conditionally active form of FOXP3
European Journal of Immunology
Sarah E. Allan, George X. Song-Zhao, Thomas Abraham, Alicia N. McMurchy, Megan K. Levings
DOI: 10.1002/eji.200838373
11/2008

The role of T-regulatory cells and Toll-like receptors in the pathogenesis of human inflammatory bowel disease
Immunology
Megan E. Himmel, Gijs Hardenberg, Ciriaco A. Piccirillo, Theodore S. Steiner, Megan K. Levings
DOI: 10.1111/j.1365-2567.2008.02939.x
10/2008

CD4+T-regulatory cells: toward therapy for human diseases
Immunological Reviews
Sarah E. Allan, Raewyn Broady, Silvia Gregori, Megan E. Himmel, Natasha Locke, Maria Grazia Roncarolo, Rosa Bacchetta, Megan K. Levings
DOI: 10.1111/j.1600-065x.2008.00634.x
06/2008

STAT5-signaling cytokines regulate the expression of FOXP3 in CD4+CD25+ regulatory T cells and CD4+CD25- effector T cells
International Immunology
Laura Passerini, Sarah E. Allan, Manuela Battaglia, Sara Di Nunzio, Alicia N. Alstad, Megan K. Levings, Maria G. Roncarolo, Rosa Bacchetta
DOI: 10.1093/intimm/dxn002
02/2008

Generation of Potent and Stable Human CD4+ T Regulatory Cells by Activation-independent Expression of FOXP3
Molecular Therapy
Sarah E Allan, Alicia N Alstad, Natacha Merindol, Natasha K Crellin, Mario Amendola, Rosa Bacchetta, Luigi Naldini, Maria Grazia Roncarolo, Hugo Soudeyns, Megan K Levings
DOI: 10.1038/sj.mt.6300341
01/2008

F.75. Molecular and Functional Studies in T Cells from Healthy Carriers of FOXP3 Mutations
Clinical Immunology
Rosa Bacchetta, Sara Di Nunzio, Lucia Beatrice Perroni, Laura Passerini, Sarah Allan, Alicia Alstad, Anne Junker, Megan Levings, Maria Grazia Roncarolo
DOI: 10.1016/j.clim.2008.03.187
01/2008

Expression of RORC2 Controls the Development of Human Th17 Cells
Clinical Immunology
Sarah Crome, Adele Wang, Megan Levings
DOI: 10.1016/j.clim.2008.03.043
01/2008

Pro-tolerogenic effects of photodynamic therapy with TH9402 on dendritic cells
Journal of Clinical Apheresis
Raewyn Broady, Jie Yu, Megan K. Levings
DOI: 10.1002/jca.20162
2008

Molecular Signalling in T Regulatory Cells
Regulatory T Cells and Clinical Application
Natasha R. Locke, Natasha K. Crellin, Megan K. Levings
DOI: 10.1007/978-0-387-77909-6_8
2008

27 Effects of IL-17 On Effector and Regultory T Cell Subsets
Cytokine
Sarah Q. Crome, Adele Wang, Megan K. Levings
DOI: 10.1016/j.cyto.2007.07.032
07/2007

Flow cytometry-based methods for studying signaling in human CD4+CD25+FOXP3+ T regulatory cells
Journal of Immunological Methods
Natasha K. Crellin, Rosa V. Garcia, Megan K. Levings
DOI: 10.1016/j.jim.2007.05.008
07/2007

Altered activation of AKT is required for the suppressive function of human CD4+CD25+ T regulatory cells
Blood
N. K. Crellin, R. V. Garcia, M. K. Levings
DOI: 10.1182/blood-2006-07-035279
03/2007

Activation-induced FOXP3 in human T effector cells does not suppress proliferation or cytokine production
International Immunology
S. E. Allan, S. Q. Crome, N. K. Crellin, L. Passerini, T. S. Steiner, R. Bacchetta, M. G. Roncarolo, M. K. Levings
DOI: 10.1093/intimm/dxm014
02/2007

Isolation, Expansion, and Characterization of Human Natural and Adaptive Regulatory T Cells
Immunological Tolerance
Silvia Gregori, Rosa Bacchetta, Laura Passerini, Megan K. Levings, Maria Grazia Roncarolo
DOI: 10.1007/978-1-59745-395-0_6
2007

Gliadin-Specific Type 1 Regulatory T Cells from the Intestinal Mucosa of Treated Celiac Patients Inhibit Pathogenic T Cells
The Journal of Immunology
C. Gianfrani, M. K. Levings, C. Sartirana, G. Mazzarella, G. Barba, D. Zanzi, A. Camarca, G. Iaquinto, N. Giardullo, S. Auricchio, R. Troncone, M.-G. Roncarolo
DOI: 10.4049/jimmunol.177.6.4178
09/2006

Interleukin-10-secreting type 1 regulatory T cells in rodents and humans
Immunological Reviews
Maria Grazia Roncarolo, Silvia Gregori, Manuela Battaglia, Rosa Bacchetta, Katharina Fleischhauer, Megan K. Levings
DOI: 10.1111/j.0105-2896.2006.00420.x
08/2006

Defining a Role for FOXP3 in Human Cd4+ T-Cells
Clinical Immunology
Sarah Allan and Laura Passerini and Rosa Bacchetta and Mario Amendola and Luigi Naldini and Maria Grazia Roncarolo and Megan Levings
DOI: 10.1016/j.clim.2006.04.525
01/2006

OR.40. Foxp3 Mutations in Children: Different Degrees of Impairment in Regulatory and Effector T-Cell Functions in Patients with Distinct Genotypes and Phenotypes
Clinical Immunology
Rosa Bacchetta, Laura Passerini, Eleonora Gambineri, Sarah Allan, Lucia Perroni, Susan Matthes-Martin, Anita Lawitschka, Steven Ziegler, Megan Levings, Maria Grazia Roncarolo
DOI: 10.1016/j.clim.2006.04.196
01/2006

OR.7. Human CD4+CD25+ T Regulatory Cells Have Altered PKB Signalling Which Correlates with Suppressive Function
Clinical Immunology
Natasha Crellin, Rosa Garcia, Megan Levings
DOI: 10.1016/j.clim.2006.04.009
01/2006

Functional Dynamics of Naturally Occurring Regulatory T Cells in Health and Autoimmunity
Advances in Immunology
DOI: 10.1016/s0065-2776(06)92003-3
2006

Human CD4+ T Cells Express TLR5 and Its Ligand Flagellin Enhances the Suppressive Capacity and Expression of FOXP3 in CD4+CD25+ T Regulatory Cells
The Journal of Immunology
N. K. Crellin, R. V. Garcia, O. Hadisfar, S. E. Allan, T. S. Steiner, M. K. Levings
DOI: 10.4049/jimmunol.175.12.8051
2005

Differentiation of Tr1 cells by immature dendritic cells requires IL-10 but not CD25+CD4+ Tr cells
Blood
M. K. Levings
DOI: 10.1182/blood-2004-03-1211
09/2004

Can we throw the master-switch in autoimmune disease?HotSpots
Clinical Genetics
Paul C Orban, Megan K Levings
DOI: 10.1034/j.1399-0004.2003.t01-2-00121.x
06/2003

Discoveries in sphingolipid metabolism, spinocerebellar ataxia and autoimmune diseaseLook into my eyes: modulating sphingolipid metabolism to reverse inherited retinal degeneration
Clinical Genetics
Liam R Brunham, Edmond YW Chan, Paul C Orban, Megan K Levings
DOI: 10.1034/j.1399-0004.2003.00121.x
06/2003

Human CD25+CD4+T Suppressor Cell Clones Produce Transforming Growth Factor ß, but not Interleukin 10, and Are Distinct from Type 1 T Regulatory Cells
The Journal of Experimental Medicine
Megan K. Levings, Romina Sangregorio, Claudia Sartirana, Anna Lisa Moschin, Manuela Battaglia, Paul C. Orban, Maria-Grazia Roncarolo
DOI: 10.1084/jem.20021139
11/2002

Growth and expansion of human T regulatory type 1 cells are independent from TCR activation but require exogenous cytokines
European Journal of Immunology
Rosa Bacchetta, Claudia Sartirana, Megan K. Levings, Claudio Bordignon, Satwant Narula, Maria-Grazia Roncarolo
DOI: 10.1002/1521-4141(200208)32:83.0.co;2-2
08/2002

The Role of IL-10 and TGF-ß in the Differentiation and Effector Function of T Regulatory Cells
International Archives of Allergy and Immunology
Megan K. Levings, Rosa Bacchetta, Ute Schulz, Maria Grazia Roncarolo
DOI: 10.1159/000067596
2002

Type 1 T regulatory cells
Immunological Reviews
Maria Grazia Roncarolo, Rosa Bacchetta, Claudio Bordignon, Satwant Narula, Megan K. Levings
DOI: 10.1034/j.1600-065x.2001.1820105.x
08/2001

Human Cd25+Cd4+T Regulatory Cells Suppress Naive and Memory T Cell Proliferation and Can Be Expanded in Vitro without Loss of Function
The Journal of Experimental Medicine
Megan K. Levings, Romina Sangregorio, Maria-Grazia Roncarolo
DOI: 10.1084/jem.193.11.1295
06/2001

IFN-  and IL-10 Induce the Differentiation of Human Type 1 T Regulatory Cells
The Journal of Immunology
M. K. Levings, R. Sangregorio, F. Galbiati, S. Squadrone, R. de Waal Malefyt, M.-G. Roncarolo
DOI: 10.4049/jimmunol.166.9.5530
05/2001

T-regulatory 1 cells: A novel subset of CD4+ T cells with immunoregulatory properties
Journal of Allergy and Clinical Immunology
Megan K Levings, Maria-Grazia Roncarolo
DOI: 10.1067/mai.2000.106635
07/2000

The role of different subsets of T regulatory cells in controlling autoimmunity
Current Opinion in Immunology
Maria-Grazia Roncarolo, Megan K Levings
DOI: 10.1016/s0952-7915(00)00162-x
2000

Insulin Receptor Substrate-2 Is the Major 170-kDa Protein Phosphorylated on Tyrosine in Response to Cytokines in Murine Lymphohemopoietic Cells
Journal of Biological Chemistry
Melanie J. Welham, Heather Bone, Megan Levings, Leslie Learmonth, Ling-Mei Wang, Kevin B. Leslie, Jacalyn H. Pierce, John W. Schrader
DOI: 10.1074/jbc.272.2.1377
01/1997

Isolation, Expansion, and Characterization of Human Natural and Adaptive Regulatory T Cells
Immunological Tolerance
Silvia Gregori, Rosa Bacchetta, Laura Passerini, Megan K. Levings, Maria Grazia Roncarolo
DOI: 10.1385/1-59745-395-1:83

Type 1 T Regulatory Cells and Their Relationship with CD4+CD25+ T Regulatory Cells
Generation and Effector Functions of Regulatory Lymphocytes
Maria Grazia Roncarolo, Silvia Gregori, Megan Levings
DOI: 10.1002/0470871628.ch9

Phenotypic and Functional Differences Between Human CD4+CD25+ and Type 1 Regulatory T Cells
CD4+CD25+ Regulatory T Cells: Origin, Function and Therapeutic Potential
M. K. Levings and M. G. Roncarolo
DOI: 10.1007/3-540-27702-1_14

Research

Current Projects
Studying the interaction between Tregs and IL-17-producing cells
Developing biomarkers to track the function of Tregs
Studying the unique cell-signalling pathways in human and mouse Tregs

Grants

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

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

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

Honours & Awards

2012 Genome Canada-CIHR Competition in Personalized Health

2016 UBC Killam Research Prize in Applied Science & Sciences

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

Research Group Members

Jessica Huang
Daphne Brockington, Clinical Trial Manager
Romy Hoeppli
Dan Wu
Anne Pesenacker
Laura Cook
Avery Lam, Doctoral Student
Nicholas Dawson
Jana Gillies
Rosa Garcia
Mitsu Komba, Lab Tech
Katie MacDonald, Doctoral Student
Majid Mojibian, Research & Development Manager
May Wong
Madeleine Speck
Kyle Reid, Student
Caroline Lamarche
Vivian Fung, Student
Sunny Chen
Marjorie Robbins
Antoine Sicard, Postdoctoral Fellow
Kirsten Ward Harstonge, Postdoctoral Fellow
Miika Hakkinen, Co-op Student
Uyen Nguyen
Dominic Boardman
Grace Zheng
Kaija Strautins, Research Coordinator
Emma McIver