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.
