Researchers in the Levings Lab
Researchers in the Levings Lab are made up of Clinician Scientists, Grad Students, Postdoctoral Fellows, Lab Technicians and Project Managers.
Investigator and Lead, Childhood Diseases Research Theme, BC Children's Hospital; Professor, Department of Surgery, University of British Columbia
Research in Dr. Levings's laboratory is focused on a novel subset of CD4+ T cells, termed T regulatory (Treg) cells, which control immune homeostasis.
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.
Research Associate and Project Manager, PhD
I majored in microbiology and biochemistry at the University of Muenster, Germany and did my doctoral work (in dubious German) with Paul Tudzynski, studying the role of active oxygen in the pathologic mechanism of the rye pathogen Claviceps purpurea (most notorious for producing the LSD precursor lysergic acid).
As a postdoc in Vancouver I switched to the field of medicine, comparing heat shock protein epitopes in pathogenic and commensal strains of Staphylcococcus- and wondering how the immune system differed between the two (remember flesh eating disease). In my second postdoc with Dr. Ted Steiner, I looked at the influence of stress (ATP, active oxygen) on intestinal cell sensing of bacterial flagellin; did strange (but gentle) things to mice to further the understanding of inflammatory bowel disease. I moved to a research associate position with Kirk Schultz, who specializes in leukemia immunotherapy. In his lab I organized his clinical research trials, ran yet more ELISAs and dabbled a bit on the side in the immunostimulatory properties of mitochondrial DNA, among other things. Finally I have landed in Megan's hardcore adaptive immunology lab where I am all about developing and standardizing assays for the clinical setting. One project aims to stratify patients with autoimmune disease based on likely response to biologicals, another deals with immune monitoring of post-transplant patients by flow cytometry.
My prevailing interest is in the conflict between self and everything that is not self (including altered self-cancer, and somebody else's self-transplant). Which covers just about everything.
Research and Development Manager, PhD
I began my professional career as a medical laboratory doctor. My strong interest in research, particularly in immunology, compelled me to enter a PhD program in immunology at the University of Ottawa. My specific interest in diabetes started when I joined the research team of Dr. Fraser Scott at the Ottawa Health Research Institute. I expanded my technical expertise and knowledge in his laboratory, which has a major focus on understanding diabetes-promoting interactions between dietary antigens, the gut immune system, and the endocrine pancreas. After receiving my PhD, I trained in the lab of Dr. Timothy Kieffer in the area of developing novel therapies for patients with diabetes. I was privileged to collaborate with our industry partners, enGene, a pioneer in gene delivery technology to mucosal tissue, and Johnson & Johnson’s Janssen BetaLogics group, an expert in developing human embryonic stem cell-based therapies for treating type 1 diabetes.
In Dr. Levings' team, I manage projects involving laboratory-based research in the area of immune regulation. The projects I work on are focused on translation to clinical applications and the initiation of first-in-human clinical trials in the fields of transplant medicine and autoimmunity. Specifically, my role involves collaborators and working with staff affiliated with industrial funding partners as well as with collaborators who are located at different sites nationally and internationally.
Rosa is in charge of the daily operations in the lab, making sure everything runs smoothly. Her research interest is on Tregs in the site of inflammation and the role of inflames microenvironment on the biology of this cells. She is looking for specific markers to distinguish these cells and their mechanism of action.
IPEX is a fatal autoimmune disease caused by a defect in the development of regulatory T cells. The disease results from mutations in FoxP3, a transcription factor which is necessary for the development of regulatory T cells. My project is aimed at understanding how the FoxP3 mutations found in IPEX lead to this regulatory T cell defect.
Jessica Qing Huang
My research currently focuses on tissue based T regulatory cells, especially on skin. Skin resident T cells were isolated donors skin biopsy. Treg characterization and cytokines profiles in skin and peripheral blood are examined in scleroderma and GvHD diseases.
As a lab technician, my role in the lab focuses on in vivo and in vitro studies, from Cell culture to technical assistance in organ transplantation in mouse models. One major project I’m assisting with is looking at Tregs that have been engineered to recognize the human HLA-A2 protein which is very important for matching transplant donors and recipients to prevent the rejection of skin transplants.
And besides taking care of our mouse colonies, I’m also helping with daily operational tasks in the lab.
Antigen recognition by T-cells is crucial for their function. My research focuses on whether engineered antigen recognition by Tregs can rescue their ability to suppress unwanted inflammation and whether antigen specific T-cell responses can be used as a prognostic tool in these incurable diseases.
My research focuses on the biology of regulatory T cells (Treg) and Th17 cells. Disruptions to the in vivo balance of these cells is a key driving force behind numerous autoimmune diseases. I am looking at the link between Tregs and Th17 cells in humans and investigating therapeutic approaches which aim to alter the balance of these cells to treat inflammatory bowel disease.
- Canadian Institutes of Health Research (CIHR) Fellowship
- Mining for Miracles Postdoctoral Fellowship (Declined)
My primary research area is the role of disease antigen-specific CD4+ T cells in intestinal autoinflammatory and infectious diseases and investigating novel cell-therapy approaches for treating inflammatory bowel disease (IBD). My key areas of investigation are:
- Determining the unique advantages of using IL-10-secreting type 1 regulatory cells as a cell-therapy for IBD.
- Exploring the utility of a parasite-derived molecule to induce stable regulatory T cells for therapeutic use.
- Understanding the role of bacterial flagellin-specific CD4+ T cells in driving inflammatory bowel disease.
- Characterizing the CD4+ T cell memory response to C. difficile infection and determining its use as a predictive diagnostic tool.
- Bertram Hoffmeister Postdoctoral Fellowship – BC Children’s Hospital, Canada
- JDRF Canadian Clinical Trial Network Postdoctoral Fellowship – JDRF, Canada
- Transplant Research Training Award – Canadian Institutes of Health Research
Postdoctoral Fellow, MD
My goal is to increase tolerance in solid organ transplant recipients by harnessing the natural properties of regulatory T cells (Tregs). Dr Levings’ lab developed a way to improve the potency of Tregs by engineering them to express a chimeric antigen receptor specific for a transplant-relevant antigen: HLA-A2. My role is to demonstrate whether A2-CAR Tregs can control allograft rejection and induce long-term transplant tolerance.
- CIHR Postdoctoral Research Award
- Société Québécoise de Néphrologie
- Council of Physicians, Dentists and Pharmacists of Maisonneuve-Rosemont Hospital
Isaac Rosado Sanchez
The success of organ transplantation depends on the administration of immunosuppressive drugs to prevent rejection of the transplanted organ. However, these drugs have many side effects that lead to cancer and infections risk. Alternatively, regulatory T cells (Treg) are suppressive cells that can be used as cellular therapy to tolerate the transplanted organ. Dr Levings’ lab has been a pioneer in the use of Chimeric Antigen Receptors (CAR) to generate organ-specific Treg cells for use as cellular therapy to prevent rejection. My research focuses on optimizing these CAR constructions for their use in Treg therapies, trying to enhance their
effectiveness and safety.
- UBC School of Biomedical Engineering Postdoctoral Fellowship Award
My research focuses on regulatory T cells (Tregs) in human disease such as type 1 diabetes and inflammatory bowel disease. I am interested in how Tregs change in response to disease treatment and how changes in Tregs may predict treatment effectiveness. I am also investigating how integrin signalling modifies Treg function and phenotype in humans.
- Juvenile Diabetes Research Foundation, Postdoctoral Fellowship
- Canadian Institutes of Health Research / Canadian Association of Gastroenterology, Postdoctoral Fellowship
After insertion of an allograft, a common complication that occurs in patients is graft versus host disease. However, there is increasing evidence that acceptance of a graft is dependent, in part, by numbers of regulatory T cells. My research involves determining whether the Treg gene signature developed in our lab can predict susceptibility of GVHD after hematopoietic stem cell transplantation.
Canadian Institutes of Health Research / Frederick Banting and Charles Best Canada Graduate Scholarship - Doctoral Award
My research focuses on novel mechanisms of Treg function. Our lab has found that human and murine Tregs produce chemokines to attract their target cells for suppression. My work aims to better understand the underlying mechanism and to characterize their defect in autoimmune disease. Additionally, we are examining the potential of Tregs to mediate tissue repair in the context of cell therapy.
- CIHR Frederick Banting and Charles Best Canada Graduate Scholarships - Doctoral Award
- CIHR Frederick Banting and Charles Best Canada Graduate Scholarships - Master’s Award
Katie N. MacDonald
We have found that discarded thymuses from children undergoing heart surgery are a rich source of Tregs for cell-based therapy. My research focuses on developing methods to isolate, expand and cryopreserve these cells that can used in clinical applications. I am also interested in investigating new conditions to further enhance Treg growth in culture.
- Canadian Institutes of Health Research / Frederick Banting and Charles Best Canada Graduate Scholarship - Doctoral Award
We have found that a pseudokinase, Trib1, is highly expressed in Tregs. Although lacking the catalytic domain for phosphorylation, the tribbles proteins can modulate various cellular processes by interacting with a number of transcription factors and signalling kinases, including FOXP3 and AKT, which are important regulators of Treg function. My project aim to establish the expression profiles of tribbles proteins and to understand their functions in human and mouse Tregs.
Canadian Institutes of Health Research / Frederick Banting and Charles Best Canada Graduate Scholarship - Doctoral Award
In animal models of type 1 diabetes (T1D), injecting regulatory T cells (Tregs) bearing islet specific T cell receptors have been shown to prevent and reduce disease. The Levings’ lab has previously shown Tregs expressing chimeric antigen receptors against HLA-A2 have potent activity and are antigen specific. My research project is to engineer antigen specific Tregs expressing chimeric antigen receptors against T1D-relevant peptide-MHC class II.
I joined the Levings Lab in 2018 as a Masters student with interests in high-dimensional flow cytometry and automated gating for flow data analysis. Using the latest 5-laser FACSymphony, I evaluate whether physical exercise improves immune recovery in patients who received an allogeneic bone marrow transplant (BMT). Ultimately, I will determine whether physical exercise can help rebuild the immune system and improve clinical outcome in the BMT population.