Relevant Thesis-Based Degree Programs
Graduate Student Supervision
Doctoral Student Supervision
Dissertations completed in 2010 or later are listed below. Please note that there is a 6-12 month delay to add the latest dissertations.
Multiple sclerosis is a chronic, inflammatory disorder of the central nervous system, thought to primarily affect persons of Caucasian ancestry. Despite growing recognition of multiple sclerosis and clinical variants such as neuromyelitis optica in persons of other ethnicities, relevant research in emerging populations is comparatively scant. Consequently, current understanding with respect to clinical outcomes and risk factors in this ethnic group is remarkably under-developed. The overarching objective of this dissertation was to address these knowledge gaps using a multi-disciplinary approach focusing on Asian-ethnic populations in Canada and China. The prevalence of multiple sclerosis in an Asian-ethnic population of Canada was found to be intermediate to that typically reported in Asia and in the general Canadian population. Longitudinal analysis also revealed an increase in incidence among females of Asian ancestry in Canada. In comparative analysis in a Canadian clinic population, long-term clinical outcomes of multiple sclerosis in patients of Asian ancestry were remarkably similar to those in non-Asian patients. Male sex and later age at onset were associated with less favourable clinical outcomes, irrespective of ethnicity or region. In immigrant and Canadian-born patients, duration of exposure to the Canadian environment prior to onset was associated with multiple sclerosis, whereas exposure to the regional environment of Asia was associated with neuromyelitis optica. Case-control analysis revealed a robust association of smoking with multiple sclerosis risk and clinical outcomes in Canadians of Asian ancestry. Genetic studies confirmed the overall low rate of familial recurrence in this ethnic group, but also identified novel variants associated with risk and clinical phenotypes. The findings underscore the importance of ethnicity-related genetic and environmental factors in modifying susceptibility to and clinical presentation of multiple sclerosis and related disorders in persons of Asian ancestry. Nevertheless, these results also suggest that the clinical trajectory in patients of Asian ancestry may be more comparable to classic clinical descriptions than previously believed. Taken together, the findings presented in this dissertation contribute new perspectives to the epidemiology and etiology of multiple sclerosis and related disorders, and advance knowledge in an emerging patient population in Canada and globally.
Master's Student Supervision
Theses completed in 2010 or later are listed below. Please note that there is a 6-12 month delay to add the latest theses.
Globally, approximately 35.6 million people live with dementia, with a yearly incident increase of approximately 7.7 million. Factoring in the aging population and increasing life expectancies, current projections predict that by 2050, global prevalence of dementia will reach 155 million. Alzheimer disease (AD) is the most common cause of dementia accounting for 60-80% of cases. AD is a complex and genetically heterogeneous condition. Most cases are the result of multifactorial inheritance with advancing age being the greatest contributor to risk; however, approximately 5% of AD occurs in the context of a dominant family history. Because there is such a strong association between young onset age (before age 60-65) and dominantly inherited AD, it is unclear how often late-onset Alzheimer disease (LOAD) is due to single gene inheritance. We hypothesize that LOAD in multi-incident families is, at times, caused by single gene mutation, in either the 3 genes known to cause early-onset AD (PSEN1, PSEN2 and APP) or genes not previously associated with AD. Family history data from attendees of a referral-based memory disorder clinic were entered into a new comprehensive database which allowed selection of thirteen families suggestive of dominantly inherited LOAD. A targeted gene panel containing the coding region of 177 genes implicated in dementia and other neurodegenerative conditions was used to screen for pathogenic mutations in our candidate families. We identified 97 missense variants and 1 nonsense variant, including mutations in PSEN1 (p.I437V), PSEN2 (p.S130L), DNAJC13 (p.N855S), DCTN1 (p.T147A) and LMNA (p.N459S). Our findings justify offering diagnostic genetic testing to individuals symptomatic for LOAD with family histories suggestive of autosomal dominant inheritance. Currently, such testing is only offered to individuals with early-onset disease. This research also provides a useful framework for ongoing gene discovery in LOAD and other dementias utilizing the family history database and population-based DNA samples available at the University of British Columbia Hospital Clinic for Alzheimer Disease and Related Disorders (UBCH-CARD).