My research (which depends critically on the collaborative contributions of many laboratory co-investigators and other clinician-scientists) aims to identify the major genetic alterations that confer risk of major psychiatric disorders (particularly schizophrenia and related psychotic illnesses) and neurodevelopmental disorders, with the hope of using this information to develop precision medicine (i.e., individualized treatment based on a mechanistic understanding of disease causation) for psychiatric illness that fails to respond to existing treatments. My main research focus is the MAGERS project (detailed below); however, I also do case-based research in adolescents and adults living with neurodevelopmental problems (such as autism spectrum disorders and learning/intellectual disabilities), which mainly involves screening using gene chip technology for potentially causative alterations in chromosomes, and the genes they impact, that might help us identify new strategies to improve cognitive and behavioral functioning of affected individuals.
MAGERS (Metabolic and Genetic Explorations in Refractory Schizophrenia)
The MAGERS (Metabolic and Genetic Explorations in Refractory Schizophrenia) study (Robert Stowe, P.I., Precilla Carrion, Co-Project Lead) is a multi-layered clinical. "-omics", and genetic counselling research project, recruiting inpatient participants from the tertiary provincial BC Psychosis Unit at UBC Hospital suffering from highly treatment-resistant schizophrenia or schizoaffective disorder. Detailed clinical phenotyping includes M.I.N.I psychiatric interviews and multidisciplinary consensus DSM-5 diagnosis, structured birth and childhood trauma histories, neurocognitive assessments, and neurological and dysmorphological examinations.
At entry, intensive biochemical screening for inborn errors of metabolism (IEMs) associated with psychosis are performed in the BCCH Biochemical Genetics Laboratory (Dr. Graham Sinclair) and in laboratories at three other hospitals, and chromosomal microarrays are performed in the Royal Colombian Hospital Cytogenetics Laboratory. Clinically actionable results of these procedures are returned to care providers, and to patient, families, and through psychiatric genetic counselling (the impact of which is also being assessed as a research outcome.
Whole blood, peripheral blood mononuclear cells, serum, plasma, and urine on participants are collected and stored under the direction of co-investigators at the BC Children's Hospital Research Institute, UBC campus, University of Victoria, and the University of Alberta, for batch small-molecule metabolomics, proteomics, immunophenotyping; and DNA and RNA extraction for whole genome and RNA sequencing. Analyses conducted and BCCHRI by MAGERS co-investigators include cytokine and inflammatory marker profiling (Dr. Clare Beasley); epigenetic analyses (whole genome methylation and GWAS chip genotyping, Dr. Michael Kobor); qPCR validation of small chromosomal variants (Dr. Colin Ross); and bioinformatics (Drs. Sara Mostafavi and Wyeth Wasserman).
A cross-validation approach, intensive phenotyping-genotype correlation, and novel bioinformatics tools will be employed for variant prioritization, with the aim of identifying potent genomic risk variants indexing key mechanistic derangements driving psychosis in affected individuals, and indexing tractable treatment targets (such as ion channels, neurotransmitter systems, and synaptic and dendritic function and plasticity, and major cellular and immunomodulatory pathways) that can be used to develop precision medicine for psychosis that fails to respond to existing treatment approaches.