Dr. Rachel Wevrick, PhD

portrait of Rachel Wevrick


8-16 Medical Sciences Building
Lab: 780-492-5499
Email: rwevrick@ualberta.ca
Dr. Wevrick is a Professor of Medical Genetics whose research focusses on the genetics and pathophysiology of neurodevelopmental disorders, including Prader-Willi syndrome and Schaaf-Yang syndrome. She has a B.Sc. from Queen’s University, a Ph.D. from the University of Toronto, and completed postdoctoral fellowships at the Hospital for Sick Children in Toronto and Stanford University. Dr. Wevrick sits on the Scientific Board of Directors for the Foundation for Prader-Willi Research (USA) and is Scientific Advisor to the Board of Directors for the Foundation for Prader-Willi Research (Canada). She is also a member of the Preclinical Animal Network for Prader-Willi syndrome and has written extensively about cellular and animal models of Prader-Willi syndrome.

Research in the Wevrick Laboratory is funded by the Canadian Institutes of Health Research, the Natural Sciences and Engineering Research Council of Canada, the Foundation for Prader-Willi Research and the Womens and Children Health Research Institute.

Genetic basis of Neurodevelopmental Disorders

My research program is focused on the genetic, molecular, and physiological basis of abnormal neurodevelopment, growth and metabolism in developmental disorders affecting children.

Specific areas of interest include:

  1. Prader-Willi syndrome (PWS) is a sporadic genetic disorder affecting about 1 in 10,000 children. PWS is caused by the loss of function of a set of genes on human chromosome 15q11-q13. Children with PWS present after birth with poor muscle tone and failure to thrive, and later develop sleep and circadian rhythm dysfunction, maladaptive behavior, intellectual disability, endocrine dysfunction, and unrelenting hunger that can lead to life-threatening obesity. Two of these genes, Necdin and MAGEL2, encode proteins of the "MAGE" (melanoma antigen) family that enhance the activity of RING E3 ubiquitin ligase complexes. Using cell and animal models, my group showed that mice missing the Magel2 gene have behavioral abnormalities, changes in brain structure and neuropeptide content, endocrine dysfunction, leptin insensitivity, and obesity, and that mice lacking Necdin have neuronal abnormalities resulting in respiratory distress. We are actively investigating whether Magel2 functions in regulatory networks that are implicated in metabolism and obesity, muscle development and function, and intellectual disability and autism spectrum disorders.
  2. Translational research in PWS. We are using two strains of mice, deficient for either the Necdin and Magel2 genes, to test therapeutics in a preclinical setting in advance of or concurrently with clinical trials ongoing to treat Prader-Willi syndrome. This translational program aims to shorten the timeline between basic discovery and clinical implementation through the investigation of therapeutics in preclinical animal models of PWS.
  3. Schaaf-Yang syndrome is very rare genetic disorder caused by mutations in the MAGEL2 gene (also disrupted in PWS). Children with Schaaf-Yang syndrome present with severe hypotonia and limb contractures, intellectual disability and autism spectrum disorder, endocrine dysfunction, and maladaptive behavior. We discovered the MAGEL2 gene and its role in neurodevelopmental processes, and continue to use biochemical, cell biological and whole animal studies to determine the effect of loss of MAGEL2 function.
  4. Other neurodevelopmental disabilities are caused by de novo or inherited genetic mutations that affect the function of the brain and nervous system. We are investigating the genetic and cellular basis of neurodevelopmental disorders, including Bardet-Biedl syndrome, Tourette syndrome, and severe early onset obesity with intellectual disability.

Selected Publications:

  1. M.R. Sanderson, K.E Badior, R. P. Fahlman and R. Wevrick (2020). The necdin interactome: evaluating the effect of amino acid substitutions in necdin using proximity-dependent biotinylation (BioID) and mass spectrometry. Human Genetics, in press.
  2. K.V. Carias, M. Zoeteman, A. Seewald, M.R. Sanderson, J.M. Bischof, and R. Wevrick (2020) A MAGEL2-deubiquitinase complex regulates the ubiquitination of circadian rhythm protein CRY1. PLoS One 15(4):e0230874. PMID: 32315313.
  3. J. M. Bischof and R. Wevrick (2018). Chronic diazoxide treatment decreases fat mass and improves endurance capacity in an obese mouse model of Prader-Willi syndrome. Molecular Genetics and Metabolism 123, 511-517. PMID: 29506955
  4. T. M. Wijesuriya, L. De Ceuninck, D. Masschaele, M. R. Sanderson, K. V. Carias, J. Tavernier, and R. Wevrick (2017). The Prader-Willi syndrome proteins MAGEL2 and necdin regulate leptin receptor cell surface abundance through ubiquitination pathways. Hum. Mol. Genet., 26, 4215–4230. PMID: 28973533
  5. A.A. Kamaludin, C. Smolarchuk, J. M. Bischof, R. Eggert, J.J. Greer, J. Ren, J.J. Lee, T. Yokota, F.B. Berry, and R. Wevrick (2017) Muscle dysfunction caused by loss of Magel2 in a mouse model of Prader-Willi and Schaaf-Yang syndromes. Hum. Mol. Genet. 25: 3798-3809. PMID: 27436578
  6. C. Luck, M.H. Vitaterna, and R. Wevrick (2016) Dopamine pathway imbalance in mice lacking Magel2, a Prader-Willi syndrome candidate gene. Behavioral Neuroscience 130:448-59 PMID: 27254754.
  7. J.M. Bischof, L.H.T. Van der Ploeg, W.F. Colmers and R. Wevrick (2016) Magel2-null mice are hyper-responsive to setmelanotide, a melanocortin 4 receptor agonist. Br. J. Pharm 173:2614-2621. PMID: 27339818.
Jocelyn Bischof - Chemical Technologist
Matthea Sanderson - PhD 2020
Vanessa Carias - PhD 2019
Tishani Methsala Wijesuriya - MSc 2017
Ain Adilliah Kamaludin - MSc 2016
Chloe Luck Gibson - MSc 2016
Igor Pravdivyi - MSc 2014
Xiao Li - PhD 2014
Julia Devos - MSc 2012
Rebecca Mercer - PhD 2012
Sara Weselake - MSc 2010
Alysa Tennese - MD/PhD 2010
Jason Bush - PhD 2010
Megan O'Neill - MSc 2007
Jason Lau - PhD 2005
Syann Lee - PhD 2003
Meredith Hanel - PhD 2002