Immune Disorders

Multiple sclerosis (MS) is the most common cause of neurological disability in young adults, other than trauma, with over two million people affected worldwide. Approximately 100,000 Canadians have MS, a rate that is nine times higher than the global average. MS symptoms vary widely and may affect vision, hearing, cognition, balance, and movement; negatively affecting many aspects of quality of life. To date, there is no cure or prevention for MS.

Our immune system is our chief defense against infection, but it is a double-edged sword. Inappropriate or over-exuberant immune responses can be harmful or even fatal. The optimal response is one that is strong enough to clear the pathogen but not so strong that it also kills the host.  Dr. Perona-Wright is working to understand how this balance is achieved by studying a family of signalling molecules known as cytokines, soluble messengers used by cells of the immune system to communicate with one another.

Dr. Laura Sly’s research program aims to improve our understanding of inflammatory bowel disease pathology and to identify and validate novel therapeutic approaches that will improve patient care. Her team has been investigating the role of SH2-containing Inositol Phosphatase (SHIP) in intestinal inflammation. SHIP is a protein that regulates enzymes involved in immune cell signaling. Sly’s research has shown that SHIP-deficient macrophages are hyper-responsive to IL-4, which drives them to an alternatively activated or M2 phenotype.

Millions of newborns and infants die each year from infectious diseases. Many of these deaths are preventable, and analysis of the immune development of children can help define paths for medical intervention that may save lives.

Malignant lymphomas are the fifth most frequent cancer in humans, affecting patients of all ages. Despite generally effective treatments, a significant number of patients still die from the progressive disease. Interactions of the malignant cells with cells of the tumor microenvironment are increasingly recognized to play a pivotal role in the development of many lymphoma subtypes. However, the clinical potential of an improved understanding of microenvironment-related biology remains largely untapped.

HIV has tremendous capacity to mutate and evolve due to the body’s immune response. However, the extent to which the virus has adapted to its human hosts over the course of the pandemic remains poorly understood. Repeated cycles of immune selection and transmission may allow the accumulation of key “escape mutations” — changes in the viral genome that help HIV evade the body’s defences.

Asthma is a respiratory disease that afflicts more than two million Canadians. Asthmatics experience both airway inflammation and changes in the airway structure, called airway remodeling, when they inhale allergens, pollutants and other insults, and this leads to an exacerbation. The airway epithelium is the first site of contact for inhaled substances and has been shown to be different in asthmatics than in non-asthmatics.

Chronic myelogenous leukemia (CML) is a cancer of the white blood cells. The disease starts when genetic changes in blood stem cells (hematopoietic stem cells, or HSCs) cause them to become malignant (leukemic stem cells) and grow uncontrollably. Normally, HSCs make all the white and red blood cells that function to protect our bodies from infections and to carry oxygen and nutrients to other cells in the body. In CML, leukemic stem cells crowd out all other cells in the bone marrow, leading to illness and eventually, if uncontrolled, death in the patient.

Multiple sclerosis (MS) is a relatively common neurological disease. Because of its chronic nature and because it typically first appears in people in their mid 20s to 30s, people with MS are usually expected to live for many years following disease onset. Little is known about survival expectations, predictors of long-term survival, how survival is influenced by MS drug therapies, and causes of death in this population. Ever since immunomodulatory therapies first became available to Canadian MS patients in the mid 1990s, there has been a rapid uptake of these drugs.

Lungs are for life. Unfortunately, the most frequent long-term illnesses in children and babies are respiratory system conditions. Children's lungs can be damaged in many ways: bacterial and viral infections, asthma, or faulty genes causing thick mucus to accumulate in the lungs of children with cystic fibrosis. Even the oxygen and artificial ventilation needed to sustain the lives of premature babies can cause lasting lung damage.

Organ transplantation is a life-saving procedure for many individuals. Unfortunately, the long-term success of this procedure is compromised by the rejection of the transplanted organ(s) by the recipient's immune system. T cells are specialized cells of the immune system that protect against infections but that recognize and damage transplanted organs. Understanding how T cell responses are controlled will help to develop new methods to increase the long-term and specific acceptance of transplanted organs.

In Canada, severe infection, or sepsis, is the most common acute illness causing death. Patients with severe infections can go into shock as a result of progressive cardiac collapse and can die within 24 to 48 hours. The mortality rate of sepsis is 40%. The fact that this rate has not changed in the last 30 years illustrates that very little is known about how infection causes cardiovascular dysfunction and that very little is known about the best ways to prevent this from occurring.

The study of the cellular basis of antibody-mediated immunity in infection is an exciting, emerging field of research that has profound implications for our understanding of host-virus interactions, protective immunity and HIV vaccine design. Antibodies are proteins that are produced by plasma cells and bind to molecules on the surface of invading pathogens, flagging them for destruction.

Dr. Kelly McNagny studies the CD34 family of molecules: CD34, Podocalyxin, and Endoglycan. First identified solely as markers of blood stem cells and blood vessels, McNagny’s research has shown that they are also present on a variety of other cell types in the body. In particular, they are found on cells that play an important role in inflammatory diseases like asthma, allergies, arthritis, multiple sclerosis, intestinal infections and cancer.