Here are the projects chosen for funding in 2020:
Harnessing Population-Based Electronic Health-care Records to Construct Family Health Histories for Accurate Disease Risk Prediction and Heritability Estimation
Predicting who is likely to be diagnosed with a common chronic disease, such as heart disease, is important for tailoring treatments to patients and communicating risk to health-care providers and patients. A family history of a common chronic disease is one of the strongest predictors of future disease risk. Manitoba is unique worldwide in its ability to use longitudinal electronic health-care data spanning almost 50 years to construct objectively measured, complete lifetime family health histories for the entire Manitoba population.
Our research aims to efficiently construct lifetime histories of multiple chronic diseases for parents and offspring using health-care data. We will use these health histories to build models to accurately predict offspring risk of diabetes, heart disease and asthma, and estimate what proportion of these common chronic diseases are heritable.
Family health histories are a key component of innovations in precision health care, which aims to offer tailored care to patients. Our research has value for clinicians as they counsel patients, so that they can choose appropriate treatment options. It will inform the work of epidemiologists who conduct surveillance on disease burden and outcomes for at-risk populations, as well as policy makers who seek to develop and implement cost-effective disease prevention programs.
Developing a Living Laboratory in Pediatric Rehabilitation Research: A New Paradigm for Integrated Knowledge Exchange and Patient Engagement in Research
This project catalyzes a new interdisciplinary partnership towards a novel knowledge generation-exchange and mobilization paradigm for pediatric rehabilitation research. This innovation will take the form of a living laboratory (LL) proof-of-concept – an open information sharing system capable of sourcing and communicating evidence to and from diverse stakeholders.
LLs are underdeveloped in health care and could be critical towards overcoming documented deficiencies in knowledge translation, such as the reported 17-year lag-time from research production to its use in practice; exclusion of lived experience research; neglect of stakeholder priorities; and overreliance on linear and non-engaging methods of information sharing.
Data on stakeholder research and knowledge exchange priorities will be attained using mixed methods research approaches integrating narrative (seven focus groups) and statistical data (e-surveys to 445 caregivers, siblings, youth and clinicians). Data will inform the development of three LL proof-of-concepts co-designed with our patient advisory council and with rehabilitation engineering at Specialized Services for Children and Youth, a consolidated hub for pediatric rehabilitation services. The three proof-of-concepts will be unveiled for public engagement and voting.
As one of the first clinically embedded LLs of its kind, this work will provide access points for integrated knowledge translation, data on stakeholder knowledge exchange priorities, and provide the LL proof-of-concept necessary to leverage future funding, generate data for a potential research theme within the Children’s Hospital Research Institute of Manitoba, and inform development, application and evaluation of future LLs across pediatric care contexts.
A Multi-omic Study of the Human Brain to Uncover the Mechanism of Rett Syndrome
Rett syndrome (RTT) is a severe and progressive neurodevelopmental disorder in females. RTT patients appear normal at birth, but exhibit disease-associated symptoms within the first six to 18 months of life. Although the underlying mechanism of disease is not fully clear, we know that it is caused by mutation in a gene called MECP2. MeCP2, a protein, is an important factor in the brain that binds and reads molecular modifications on the genomic DNA.
Currently, RTT has no cure and it is not fully clear how molecular deficiencies at the cellular level cause impaired brain function in the affected patients. The novelty of our approach is to perform an unbiased genome-wide multi-omic study of the human RTT brain (compared to age-/sex-matched controls). Our multi-level global analysis of DNA, RNA and proteins will be further investigated in relevant human and murine model systems through a combination of molecular and cellular studies.
In addition to RTT, MeCP2 gain-of-function mutation leads to MECP2-duplication syndrome (MDS) and its alerted expression is associated with autism spectrum disorders (ASD) and fetal alcohol spectrum disorders (FASD). The results of our studies will not only be important for RTT, but will also shed light into the pathobiology of MDS, ASD and FASD, which currently have no cure.