Megan K. Levings

Key Research Areas
Associated Researchers
Associated Organizations

Recent Research Projects

Molecular and cellular biology of T regulatory cells

2017/18-2018/19 • $948,814 • PI
The goal of my research is to understand how our immune system regulates itself and to use this information to develop new ways to treat patients with immune-related diseases, such as autoimmunity or transplant rejection. A healthy immune system must strike a balance between attacking infectious...

Canadian Donation and Transplantation Research Program (CDTRP): Maximizing benefits through national infrastructure and sustainability planning

2018/19 • $583,334 • PI,Other
Transplantation is used much more broadly to treat diseases than most Canadians realize. No longer is it restricted to people with organ failure. Instead, it is poised to become the preferred treatment for many chronic diseases and blood cancers. Nonetheless, challenges remain, such as the 50%...

Examining the role of helper T cell immunity in Clostridium difficile infection

2017/18-2018/19 • $380,588 • PI,CO
Clostridium difficile infection (CDI) is the leading cause of hospital-acquired diarrhea in developed countries and a major source of morbidity, mortality, and health care costs. CDI classically develops following ingestion of spores spread from other patients (usually in the health care...

Development of immunologic tools for Clostridium difficile diagnosis and prognosis

2016/17-2018/19 • $300,000 • PI,CO
Clostridium difficile (C. diff) is the major cause of diarrhea in people in health care settings. It is considered a top priority pathogen for research by Canada and the USA. C. diff infection (CDI) usually happens after people ingest the bacteria spread from other patients and then receive...

Canadian Autoimmunity Standardization Core (CAN-ASC)

2018/19 • $200,000 • PI,CO
To stay healthy, we need to have an immune system that works properly: it needs to attack foreign cells, but leave our own cells alone. If our immune system attacks our cells, it causes an illness called an autoimmune disease. There are many types of autoimmune disease, including type 1...

Generation of a bacteria-specific chimeric antigen receptor: A novel approach to immunotherapy for Inflammatory Bowel Disease.

2015/16-2018/19 • $166,667 • Scholarship/Fellowship,Other
Autoimmune diseases occur when the patient's immune system attacks and destroys the body's tissues. Inflammatory bowel disease (IBD) is one such disease and consists of several different conditions united by common symptoms of gut inflammation. Over time, inflammation damages the lining of the...

Defining the biology and therapeutic potential of human T regulatory cells with tissue repair function

2017/18-2018/19 • $105,000 • Scholarship/Fellowship,Other
Transplantation can be a life-saving treatment for patients in organ failure. Unfortunately, transplant rejection, when the patient's immune system destroys the new organ, is a major cause of illness and death. Patients must take anti-rejection drugs for the rest of their life, which do not...

Tailoring antigen-specific regulatory T cells for use in transplantation

2017/18-2018/19 • $97,500 • Scholarship/Fellowship,Other
Transplantation is the best and sometimes only treatment for end-stage organ failure. In the last ten years, the lives of more than 20,000 Canadians have been improved, extended, or saved by donated organs. Immunosuppressive drugs make transplantation possible, but since these drugs cannot...

Alloantigen-specific regulatory T cells generated with a chimeric antigen receptor: ability to prevent the humoral alloimmune response

2017/18-2018/19 • $66,667 • Scholarship/Fellowship,Other
Pathologies linked to end-stage organ failure represent the second cause of morbi-mortality worldwide and have major socio-economic consequences. Transplantation, which consists in the substitution of a defective organ by a functioning graft retrieved from a donor, is the best therapeutic...

Engineering flagellin-specific Tregs to restore intestinal homeostasis in IBD

2018/19 • $45,000 • Scholarship/Fellowship,Other
Inflammatory bowel disease (IBD) is a group of severe, incurable chronic conditions which affect approximately 1/150 Canadians. IBD results from uncontrolled inflammation in the gut, causing symptoms such as diarrhoea, abdominal pain, bleeding and weight loss. IBD is driven by an imbalance of...

Understanding the role of a4ß7+ Tregs in the development and treatment of inflammatory bowel disease

2018/19 • $22,500 • Scholarship/Fellowship,Other
Canada has some of the highest rates of inflammatory bowel disease (IBD) in the world. The causes of IBD are complex, but one likely factor is an imbalance in gut immune responses. Immune cells, specifically the subset of immune cells called T cells, are of particular importance. There are two...

Innate and adaptive immune regulation in human type 1 diabetes

2018/19 • $20,000 • PI
Type 1 diabetes (T1D) is an autoimmune disease that is caused by the immune system mistakenly killing cells in the pancreas which produce insulin. Without insulin, the body cannot regulate blood sugar and this can be life threatening. Insulin can be replaced by daily injections, but this...

The Canadian National Transplant Research Program: Increasing Donation and Improving Transplantation Outcomes

2013/14-2017/18 • $11,250,000 • PI,CO,Other
Organ and bone marrow transplants are well-established treatments for patients with incurable medical conditions. However, major gaps and obstacles prevent transplantation from being fully effective. We need to develop new knowledge, policies and health care practices to overcome these barriers....

Manipulating immune regulation to improve the success of hematopoietic stem cell transplantation.

2016/17-2017/18 • $105,000 • Scholarship/Fellowship,Other
For many blood cancer patients, hematopoietic stem cell transplantation (HSCT, also known as bone marrow transplantation) is the only option for a cure. HSCT works by replacing the patient's blood stem cells with new blood stem cells from a donor. The donated blood stem cells give rise to a new...

Molecular regulation of regulatory T cell function in visceral adipose tissue

2016/17-2017/18 • $105,000 • Scholarship/Fellowship,Other
Type 2 diabetes (T2D) accounts for 90% of the 382 million cases of diabetes worldwide, a staggering number that continues to rise. T2D increases the risk of heart attacks, strokes, amputation, kidney failure and blindness. This disease is a major burden to the health care system and the...

Tailoring Regulatory T cells for Transplantation Tolerance

2017/18 • $40,927 • PI
Transplantation is the best treatment for end-stage organ failure. In the past ten years, more than 20,000 Canadians have had their lives improved or saved by donated organs. Organ transplantation is only possible because immunosuppressive drugs prevent rejection, but these drugs also bring...

Canadian Autoimmunity Standardization Core (CAN-ASC)

2017/18 • $25,000 • PI,CO
A functional immune system is essential for health. In a process called immune tolerance, it fends off dangerous foreign substances but leaves the body's own tissues untouched. Failure of immune tolerance causes chronic autoimmune diseases in which the immune system sees the body's own cells as...

Molecular and cellular biology of T regulatory cells

2011/12-2016/17 • $635,118 • PI
The immune system has a remarkable ability to specifically recognize "danger". The mechanisms by which the immune system discriminates between dangerous or non-dangerous proteins are highly complex and are not foolproof. When the immune systems starts to react against non-dangerous proteins,...

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.

2013/14-2016/17 • $555,957 • PI,CO
The immune system is designed to recognize the difference between harmful and non-harmful foreign proteins, and to not react against proteins that normally exist in an individual. Unfortunately, when the processes controlling these functions breakdown diseases such as autoimmunity and allergy...

Development of an immunologic tool for Clostridium difficile diagnosis and prognosis

2016/17 • $10,000 • PI,CO
Clostridium difficile (C. diff) is one of the leading causes of hospital acquired infection. C. diff infection (CDI) causes colitis, leading to diarrhea, fever, and abdominal pain, which in severe cases can be fatal. CDI is one of the major public health priorities in Canada because of the...

Transplantation Sciences Symposium (TSS) 2017

2016/17 • $8,250 • PI,CO
Transplantation is one of the major medical advances of the previous century and has significantly improved or saved the lives of thousands of Canadians. Although transplantation is now often considered a "standard therapy" for end stage organ failure, many challenges continue to limit this...

Assessment of the role of integrins in the modulation of phenotype, function and trafficking of human T cells in inflammatory bowel disease

2016/17 • $1,250 • Scholarship/Fellowship,Other
Inflammatory bowel disease (IBD) is the collective term used to describe two chronically occurring diseases of the intestine, Crohn's disease (CD) and ulcerative colitis (UC). Canada has one of the highest rates of IBD in the world, and the disease burden in 2012 was estimated to be $2.8...

Define the role of regulatory T cells in modulating inflammasome activity

2012/13-2015/16 • $114,231 • Scholarship/Fellowship,Other
Inflammatory bowel disease (IBD) is an incurable inflammatory disorder that constitutes a significant public health burden in Canada. What causes IBD is unknown, but it is believed to be an abnormal inflammatory response that attacks the tissue in the intestinal tract. Normally, a type of white...

CIHR Strategic Training Initiative in Transplantation Research

2010/11-2014/15 • $1,625,000 • PI,CO
The objective of this proposal is to support the Strategic Health Research Training Program in Transplantation to enable research students to interact together in a multidisciplinary basis with an innovative collaborative team of research scientists, clinician-scientists and allied health...

CaPITTAL: Canadian Patient-oriented Immune Tolerance in Transplantation and Autoimmunity to improve Lives

2014/15 • $50,000 • PI,Other
A functional immune system is essential for health. In a process called immune tolerance, it fends off dangerous foreign substances but leave the body's own tissues untouched. Failure of immune tolerance causes chronic autoimmune diseases (such as multiple sclerosis (MS), lupus, and diabetes) in...

Canada Research Chair in Transplantation

2010/11-2013/14 • $325,000 • PI
Patients undergoing transplantation face serious side effects from the immunosuppressive drugs that prevent graft rejection but also non-specifically suppress the immune system. We are studying whether a type of white blood cell, known as T regulatory cells (Tregs), could be used to control...

The role of insulin in regulating immune responses in type 2 diabetes

2012/13-2013/14 • $105,000 • Scholarship/Fellowship,Other
The obesity linked type 2 diabetes (T2D) accounts for 90% of the 346 million cases of diabetes worldwide, a staggering number that will continue to rise. The long-term consequences of T2D include an increased risk of heart attacks, strokes, amputation, kidney failure and blindness. This disease...

The role of signalling pathways in maintaining T regulatory cell function

2012/13-2013/14 • $45,000 • Scholarship/Fellowship,Other
Autoimmune diseases, such as inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis and psoriasis, arise from an overactive immune response against substances and tissues normally present in the body. If this over reactivity against self persists for a long time it results in...

CIHR Team in Immunoregulation and IBD

2010/11-2012/13 • $1,125,000 • PI,CO
Approximately 20% of North Americans are affected by autoimmune or chronic inflammatory diseases, causing pain, suffering, disability, and poor quality of life. Crohn's Disease and ulcerative colitis 2 forms of human inflammatory bowel disease (IBD), are related but distinct autoimmune diseases...

Molecular and cellular biology of human TH17 cells in health and disease

2010/11-2012/13 • $333,498 • PI,CO
The immune system is designed to recognize the difference between harmful and non-harmful foreign proteins, and to not react against proteins that normally exist in an individual. Unfortunately, when the processes controlling these functions breakdown diseases such as multiple sclerosis,...

Ex vivo generation of antigen-specific human T regulatory cells with in vivo suppressive capacity.

2010/11-2011/12 • $100,000 • Scholarship/Fellowship,Other
Type 1 diabetes mellitus (T1DM) is an autoimmune disease in which insulin-secreting cells are destroyed by a type of white blood cell of the immune system called a T cell. People suffering from T1DM must receive insulin injections to maintain proper blood sugar levels. However, some patients can...

Tailoring cancer immunotherapy to avoid immune suppression

2010/11-2011/12 • $70,000 • Scholarship/Fellowship,Other
Breast cancer is the most common neoplasm affecting Canadian women. Although current therapies are having a definite impact on this illness, one-third of all women initially diagnosed with early stage breast cancer develop recurrent or metastatic breast cancer, which is presently incurable. Much...

Functional characterization and manipulation of flagellin specific T cells in inflammatory bowel disease

2010/11-2011/12 • $70,000 • Scholarship/Fellowship,Other
Crohn's disease and ulcerative colitis, two forms of Inflammatory Bowel Disease (IBD), are disorders which are believed to be caused by the cells of the immune system mistakenly attacking the tissues of the digestive tract. This phenomenon, known as autoimmunity, leads to massive inflammation of...

Regulation of Th17 Development and Function

2011/12 • $17,500 • Scholarship/Fellowship,Other
A strong immune response is important for fighting off infectious disease and preventing cancer. But sometimes the immune system is misdirected and attacks parts of the body, pollen and dust, or transplanted organs. This results in autoimmune diseases like arthritis and multiple sclerosis,...

Defining the role and therapeutic potential for regulatory T cells in controlling inflammation in type 2 diabetes

2011/12 • $17,500 • Scholarship/Fellowship,Other
Approximately 2 million Canadians suffer from type 2 diabetes (T2D). With the growing number of diabetes patients in Canada, a better treatment is needed. T2D patients suffer from insulin resistance where the body does not respond to insulin. Aside from being a metabolic disorder, diabetes is...

ImmunoVancouver 2012

2011/12 • $12,750 • PI,CO
Immunology researchers in British Columbia (BC) are located in 10 locations throughout the Vancouver area as well as in 2 locations in Victoria. Although seminars, thesis committees, and directed collaborations bring some of us together on an ad hoc basis, the full potential for synergistic...

Human T regulatory cells: Molecular dissection of their ontogeny and functions

2010/11 • $67,708 • PI
The immune system has a remarkable ability to specifically recognize "danger". The mechanisms by which the immune system discriminates between dangerous or non-dangerous proteins are highly complex and are not foolproof. When the immune systems starts to react against non-dangerous proteins,...

Immuno-Vancouver 2011

2010/11 • $10,815 • PI,CO
Immunology researchers in the Vancouver area are located at nine different sites across the city, as well as in Victoria. Although seminars, thesis committees, and collaborations bring us together on an ad hoc basis, the full potential for synergistic research interactions and collaborations...

Summer Program in Japan (2009-2010)

2010/11 • $3,525 • PI,Other
No summary

Patents

ANTI-HLA-A2 ANTIBODIES AND METHODS OF USING THE SAME

Provided are humanized anti-HLA-A2 antibodies. In certain aspects, the humanized anti-HLA-A2 antibodies are capable of constituting an antigen binding domain of a chimeric antigen receptor (CAR), where the CAR is capable of being expressed in a human cell such that the CAR specifically binds to HLA-A2. Also provided are CARs that include the humanized anti-HLA-A2 antibodies. Modified cells including the antibodies and CARs, as well as methods of using such modified cells are also provided.
Related applications: WO2018CA51167, EP20180858795

NOVEL ANTI-HLA-A2 ANTIBODIES AND USES THEREOF

The present invention relates to a novel anti-HLA-A2 antibody, and to a chimeric antigen receptor comprising said HLA-A2 antibody. The present invention further relates to an immune cell expressing said chimeric receptor antigen, and to therapeutic uses thereof, in particular for treating or preventing graft rejection or GVHD.
Related applications: WO2018CA51174, EP20180859115