Inflammatory bowel disease (IBD) is an incurable disease that affects about 230,000 Canadians. People with IBD suffer from diarrhea, abdominal pain, weight loss, intestinal blockages, and other complications. Current treatments can control symptoms in many people, but they are not curative, and can have side effects like increased risk of infections. The causes of IBD are so far unknown.
People with IBD appear to have abnormal immune responses to the bacteria (microbes) that normally live in the intestine. This response involves blood cells, called helper T cells, that react to microbes, especially when they are not suppressed properly by another type of T cell that inhibits inflammation (known as T-regulatory cells, or Tregs).
Dr. Levings will develop a new IBD treatment that captures the natural ability of Tregs to control inflammation, using a new technology called Chimeric Antigen Receptors (CARs) which has shown promising results in cancer studies. The technology changes Tregs in such a way that they treat intestinal inflammation without affecting the rest of the body’s immune system.
Dr. Levings has validated this technology in a laboratory setting, and the next steps include testing it in animal models, creating new versions of the specific CAR she has developed, and interviewing and surveying physicians and patients to find out how receptive they would be to using CAR Treg therapy for IBD.
Dr. Sadarangani's research focuses on preventing severe illness and death in children by ensuring best use of vaccines to protect against three serious infections (meningococcal, pneumococcal, pertussis) which cause blood poisoning, meningitis and whooping cough.
Vaccines have reduced these infections, but we dont know if we are usng the optimal number and timing of dses. Sadarangani's goals are to ensure optimal use of these vaccines and aid development of future vaccines.
The project will:
- Compare the current three doses of pneumococcal vaccine given to infants against two doses. If there is no difference using two doses would mean fewer injections and lower cost.
- Compare the response to meningococcal vaccine in adolescents who have received 1, 2 or 3 previous doses, and compare the three available vaccines to identify any differences between them.
- Compare the effectiveness of pertussis vaccinefor whooping cough at different times of pregnancy to confirm the best time to immunize to protect the infant
- Examine the genetics of the pneumococcal bacteria to understand its transmission and evolution.
This research will improve vaccine schedules and help design future vaccines, ensuring that children continue to be protected against these devastating infections.
Primary immunodeficiencies (PIDs) are a group of conditions in which part of the immune system is either missing or does not function normally. Those affected by PIDs may suffer from recurrent infections, autoimmune disease (where the immune system attacks the body's own tissues), and certain cancers. These conditions are not rare; affecting 1:2,000 to 1:10,000 people, with nearly half of cases diagnosed in adulthood. Too often, adults with PIDs undergo a painful journey that spans decades in search of a diagnosis. Without knowing the cause of their immune deficiency, adults with PIDs may not receive life-changing treatment.
Our research program will address these challenges using precision medicine: an exciting way of identifying the cause of the disease and finding treatments that specifically target the underlying problem. We will perform next generation sequencing, a method to quickly read genetic material, on adults with PIDs where the underlying cause is undiagnosed. If a new change in a gene (mutation) is identified, we will perform specialized experiments to prove that the mutation is indeed responsible for the patient's symptoms. We will then look for targeted treatments to address the specific cause of that patient's illness.
By harnessing the power of personalized genetics and precision medicine, our goal is to improve outcomes for adults suffering from PIDs.
Drug treatments are essential for the survival of cancer patients. Unfortunately, medications needed for treatment can also cause permanent disabling side effects, severely impacting on the quality of life of patients already suffering the devastating consequences of cancer.
Although platinum-based drugs such as cisplatin are highly effective and are the most frequently used class of cancer medications, they are also accompanied by severe side effects. In fact, up to 80% of patients treated with cisplatin lose some ability to hear and/or experience kidney injury.
If clinicians were able to predict which patients are most likely to experience these side effects before prescribing cisplatin, they could take measures to avoid their occurrence. Pharmacogenomics, the study of how genetic differences influence why we respond differently to medications, aims to provide clinicians with this predictive information.
Dr. Drogemoller will investigate patients receiving cisplatin to identify the genetic and clinical variables that are associated with high risk of kidney failure and hearing loss. She will use these results to guide the development of predictive tests and novel treatment strategies. The results of this research will allow for the implementation of personalized treatment strategies which optimize benefits and reduce the chance of harm for cancer patients.
Patients with Inflammatory Bowel Disease (IBD) suffer bouts of extreme gut inflammation that disrupt the population of bacteria in their intestines. Consequently, IBD patients often have fewer beneficial bacteria and suffer an overgrowth of potentially dangerous bacteria. In healthy individuals, such responses are typically prevented by SIGIRR, a protein made by the cells that line the gut.
SIGIRR acts by suppressing mechanisms that drive inflammation. Loss of SIGIRR dramatically increases inflammation and drives bacterial imbalance. The inflammation can become so severe that gut tissue can become necrotic. Currently, there is no way to promote the beneficial actions of SIGIRR in the gut. Recently, however, a newly recognized anti-inflammatory compound called interleukin (IL)-37 has been shown to interact with SIGIRR to inhibit inflammatory responses in human cells.
Dr. Allaire will test whether IL-37 stimulates SIGIRR to: control inflammation and suppress bacterial killing responses in the cells that line the gut; protect mice from experimentally-induced IBD; and promote normal gut microbe balance. Results from this study will include an evaluation of the potential for IL-37 to act as a new therapeutic for patients with IBD.
Diabetes is one of the most common chronic diseases among adults, children and youth. In 2008/09, the Canadian Chronic Disease Surveillance System reported 2,359,252 cases of diagnosed diabetes in Canada and a prevalence of 5.4% in British Columbia. Rates of type 1 diabetes (T1D) among children and youth have been on the rise globally. Poor control of diabetes leads to various complications such as cardiovascular disease, stroke, blindness and renal failure, resulting in a shorter and a reduced quality of life.
One of the major pathologies in diabetes is a deficiency of insulin, which is secreted from pancreatic beta cells. Patients with T1D require insulin therapy throughout their life because most of their beta cells are destroyed by autoimmune attack. Even through insulin treatment, reduced glycemic control makes complications and hypoglycemia-induced coma more likely.
Islet transplantation is a promising therapy for T1D that removes the need for insulin therapy. However, some limitations remain such as the supply of donor islets, the need for lifelong systemic immune suppression, and graft failure. Today, human embryonic stem cell (hESC)-derived surrogate beta cells are in clinical trials; however, it is likely that these cells will not be protected from immune attack.
Dr. Sasaki will generate CRISPR-Cas9-edited hESCs that can be differentiated to beta cells that express CCL22 in order to protect hESC-derived islet cell graft from immune attack. If this approach is successful, the results of this study will further the optimization of functional and immune-tolerant surrogate beta cells, which will help pave the way towards a cure for T1D.
