My current research activities are distributed between three project areas:
I am completing genomic analysis of a familial pediatric gastrointestinal disorder which has been characterized in a large kindred of more than 100 individuals.
This potentially fatal enteropathy is attributed to an intragenic in-frame duplication, which results in a highly-penetrant dominant gain-of-function modification of the APOA4 protein.
Whole genome sequencing will clarify the role of APOA4 in conjunction with possible secondary phenotype modifiers. If the APOA4 variant is confirmed to be the nominal cause of this condition, evidence from animal models suggests that oral administration of functional APOA4 will completely attenuate life-threatening episodes of this disorder.
This will also add considerably to our understanding of the role of apolipoproteins in inflammatory disease.
Health impact of hereditary cardiac disease management
Approximately a quarter of sudden cardiac death in the young can be attributed to a diagnosis of long QT syndrome (LQTS), catecholaminergic polymorphic ventricular tachycardia (CPVT), hypertrophic cardiomyopathy (HCM), or arrhythmogenic right ventricular cardiomyopathy (ARVC).
Exercise has been implicated as a trigger for sudden cardiac arrest for each of these conditions and as a result guidelines have been published regarding physical activity restrictions.
The published guidelines challenge the current recommendations by Health Canada which emphasize the importance of daily vigorous physical activity aimed at reducing the risk of obesity and related morbidity.
I am co-supervising a doctoral graduate research project that assesses the impact of exercise restrictions with regard to weight status, physical activity level and health related quality of life (HRQL) in these pediatric populations.
This work will determine whether exercise restrictions implemented to decrease the risk of sudden cardiac arrest for children/adolescents/young adults with LQTS, CPVT, HCM and ARVC, lead to increased body mass index, decreased physical activity levels, and decreased HRQL. It will also inform current practices that are highly variable in-light of guideline inconsistencies.
Implementation of high resolution low-cost diagnostics
I have had ongoing project work with collaborators at the Centres for Disease Control (CDC) in Zhejiang Province, China.
We have been developing targeted systems to allow for relatively low-cost molecular diagnostics to augment existing screening programs, and are currently in the process of validating a novel multiplex mass array assay to provide high-resolution diagnoses of Y chromosome infertility.
I am the principal investigator on this project, which was recently awarded a development grant from the Hangzhou Economic and Technological Development Zone Talent Technology Bureau.
The design of low-cost, high-utility assays, helps to broaden the repertoire of public health services provided by this provincial CDC with a catchment population of approximately 64 million people.
It also provides much needed expertise for their technical staff, as they work to enhance the role of molecular diagnostics in their operations.