Dr. Galen Wright
Department of Pharmacology & Therapeutics
Neuroscience Research Program
Kleysen Institute for Advanced Medicine
Health Sciences Centre and University of Manitoba
710 William Avenue, SR440
Winnipeg, MB R3E 0Z3
***Currently accepting applications from interested graduate students and postdoctoral fellows. Expertise in either genomics, bioinformatics or gene editing (CRISPR-Cas9) would be an asset. Please send a short cover letter explaining why you are interested in joining the lab, along with a recent CV***
Dr. Wright is broadly interested in elucidating genetic factors that contribute towards fundamental human biology, disease and drug response through the application of bioinformatic analyses to large-scale genomic data. The results of these computational analyses are then used to inform downstream functional validation experiments. Insights obtained from this research lead to a better understanding of human biology, the identification of novel therapeutic targets, as well as improved risk prediction models. Two areas of key focus include:
1) Precision medicine approaches in neurological disorders
Neurological disorders present a substantial healthcare concern, contributing to an estimated 7% of the total global burden of disease. Furthermore, with an aging population, these statistics will continue to grow over time. This burden is exacerbated by the limited treatment options that are currently available to modify disease.
Efforts to identify novel therapeutics for neurological conditions have been met with high failure rates in drug development pipelines, mainly due to a lack of efficacy. However, recent studies have shown that the incorporation of human genetic evidence in drug target selection can improve the success rates of drug trials. Fine-mapping of genome-wide association study signals from large scale studies of neurodegenerative disorders with multi-omic information therefore provides a compelling approach to inform drug target identification. The results of these analyses are then used to prioritize molecular functional work, which includes gene editing in cell lines and single cell sequencing in disease-relevant tissues in animal models. Neurodegenerative disorders that are studied in this manner include amyotrophic lateral sclerosis, Huntington disease and spinocerebellar ataxias.
Finally, other genomic projects include the assessment of disease modifying therapies to treat neurological conditions such as multiple sclerosis, as well as adverse drug reactions that influence the central nervous system.
2) DNA repair in the brain
Organisms are constantly exposed to endogenous and environmental agents, which cause damage to their DNA. Complex pathways are involved in the detection and repair of these genetic lesions, tens of thousands of which occur daily in individual humans. DNA repair in the brain is therefore an essential process for life as it ensures that DNA damage caused by the high-energy consumption in this tissue is properly repaired. These pathways have been shown to be involved in modifying neurodegenerative disorders such as Huntington disease, as well as fundamental biological processes such as aging. Although the field of DNA repair is relatively mature, research into the brain and associated cell types warrants further research and represents a knowledge gap compared to peripheral tissues. This research program harnesses recent technological and analytical developments and includes the use of unbiased genome-wide screens and deep learning analyses with brain tissue-derived genomic data. These complementary neurogenomic approaches allow the lab to study these fundamental biological processes and identify novel genes involved in these pathways.
About Dr. Galen Wright
Dr. Wright was appointed as an Assistant Professor at the University of Manitoba in April 2020. He received his doctoral training in genetics at Stellenbosch University, South Africa, where he performed pharmacogenomics and precision medicine research in African populations. Dr. Wright then received additional training in computational biology at the South African National Bioinformatics Institute, before moving to Canada as a postdoctoral fellow at the University of British Columbia (UBC). During this fellowship, he became a member of the Canadian Pharmacogenomics Network for Drug Safety and was primarily supervised by Drs. Michael Hayden, Colin Ross and Bruce Carleton. At UBC, his research projects included investigating serious adverse drug reactions from medications used to treat neurological conditions. This work has led to the identification of highly predictive biomarkers for various adverse drug reactions, including drug-induced neurotoxicities and liver injury. Dr. Wright’s precision medicine research has also uncovered the essential role of somatic instability and DNA repair in modifying Huntington disease onset and has identified clinically-relevant genetic variants for this trait.
Dr. Wright has been supported by various funding organizations, including the Canadian Institutes of Health Research Fellowship as well as the National Research Foundation. Dr. Wright has been a co-organizer for international meetings, including an NIH-funded adverse drug reaction conference and a co-founder of the first Canadian “Genomics Hackathon”. In 2019, he was appointed a Junior Research Leader for one of the Drug Safety and Effectiveness Network CIHR Team Grants.
Analytical approaches and techniques
Bioinformatics; cell culture; gene editing (CRISPR-Cas9); genome-wide association studies; machine learning; real-time PCR; single cell sequencing; spatial transcriptomics; targeted genotyping; transcriptome-wide association studies
1. Wright G, Caron N, Ng B, Casal L, Xu X, Ooi J, Pouladi M, Mostafavi S, Ross C, Hayden M (2019) Gene expression profiles complement the analysis of genomic modifiers of the clinical onset of Huntington disease. bioRxiv 699033.
2. Wright G, Collins J, Kay C, McDonald C, Dolzhenko E, Xia Q, Bečanović K, Drögemöller B, Semaka A, Nguyen C, Trost B, Richards F, Bijlsma E, Squitieri F, Ross C, Scherer S, Eberle M, Yuen R, Hayden M (2019) Length of uninterrupted CAG, independent of polyglutamine size, results in increased somatic instability, hastening onset in Huntington disease. Am J Hum Genet 104, 1116–26.
3. Kowalec K*, Wright G*, Drögemöller B, Aminkeng F, Bhavsar A, Kingwell E, Yoshida E, Traboulsee A, Marrie R, Kremenchutzky M, Campbell T, Duquette P, Chalasani N, Wadelius M, Hallberg P, Xia Z, De Jager P, Denny J, Davis M, Ross C, Tremlett H, Carleton B (2018) Common variation near IRF6 is associated with IFN-β-induced liver injury in multiple sclerosis. Nat Genet 50, 1081-5. *Authors contributed equally to this work.
4. Wright G, Amstutz A, Drögemöller B, Shih J, Rassekh S, Hayden M, Carleton B, Ross C, the Canadian Pharmacogenomics Network for Drug Safety Consortium (2019) Pharmacogenomics of vincristine-induced peripheral neuropathy implicates pharmacokinetic and inherited neuropathy genes. Clin Pharmacol Ther 105, 402-10.
5. Wright G, Carleton B, Hayden M, Ross C (2018) The global spectrum of protein-coding pharmacogenomic diversity. Pharmacogenomics J 18, 187–95.