PhD: Department of Molecular and Medical Genetics, University of Toronto, 1987-1991
Post-doctoral fellow: Department of Genetics, The Hospital for Sick Children Research Institute, 1992
Post-doctoral fellow: Howard Hughes Medical Institute, Stanford University School of Medicine, 1993-1995
Professor: Department of Medical Genetics, University of Alberta, 1996-present
Member: Womens and Chhildren’s Health Research Institute, University of Alberta
Member, Neurosciences and Mental Health Research Institute, University of Alberta
Scientific Advisor to the Board, FPWR-Canada
Member of the Scientific Advisory Board, Prader-Willi Syndrome Association (USA)
Member of the Scientific Board of Directors, Foundation for Prader-Willi Research (USA)
Member of the Foundation for Prader-Willi Research Preclinical Animal Models Network
Member of the Foundation for Prader-Willi Research Cellular Network Program
CIHR Operating grant “Genetic and functional analysis of a mouse model of pediatric obesity”
NSERC Discovery grant “Exploration of a melanoma antigen (MAGE)-E3 ubiquitin ligase circuit governing circadian rhythm”
Women and Children’s Health Research Institute “Genetic Analysis of Children with a Dual Diagnosis of Tourette Syndrome and Autism Spectrum Disorder”
Foundation for Prader-Willi Research “Cellular role of MAGEL2 in Prader-Willi and Schaaf-Yang syndromes”
Simons Foundation Pilot Project Grant SFARI Award “Studies of MAGEL2, an autism and Prader-Willi syndrome candidate gene”
Genes and development, obesity, psychiatric disorders; mouse models for Prader-Willi syndrome; molecular basis of human genetic disorders.
Research in the Wevrick laboratory focuses on genetic disorders that affect human development. We have specific interests in pediatric obesity, developmental delay, and also study developmental aspects of gene regulation. We identified genes that are inactivated in Prader-Willi syndrome, a sporadic chromosomal disorder that causes neonatal hypotonia, developmental delay, compulsive overeating leading to obesity, and abnormalities of sleep and respiration. We are currently studying the roles of these genes in the normal development of the nervous, muscular, and endocrine systems. Two genes, necdin and MAGEL2, have specific roles in growth and differentiation. We are using mouse models to evaluate the normal roles of these proteins and the effect of their loss in Prader-Willi syndrome.
If you are interested in a graduate student or postdoctoral position in my laboratory, please contact me at email@example.com, and include your cv.
Sources of Funding:
Projects in the Wevrick laboratory are funded by the Canadian Institutes of Health Research, the Natural Sciences and Engineering Research Council, the Foundation for Prader-Willi Research, the Simons Foundation for Autism Research and the Women and Children's Health Research Institute. We also gratefully acknowledge funding from the Prader-Willi Syndrome Association of Alberta, the Foundation for Prader-Willi Research (Canada) and One SMALL Step.
Donations in support of Prader-Willi Syndrome research in the Wevrick laboratory can be made by contacting the Office of Advancement at 1-888-799-9899, emailing firstname.lastname@example.org, or by visiting "www.giving.ualberta.ca/ContactUs.aspx"
neurodevelopmental disorders, Prader-WIlli syndrome, Schaaf-Yang syndrome, brain function and development, preclinical research , cellular and animal models of disease
1. My early work focused on the identification and characterization of genes that are inactivated in Prader-Willi syndrome, and located on human chromosome 15q11-q13. These publications established that several genes are candidates for being involved in the clinical manifestations of PWS. We described the expression patterns, genomic imprinting status and potential functions of PWS region genes.
• T. Yang, T.E. Adamson, S. Leff, R. Wevrick, U. Francke, N.A. Jenkins, N.G. Copeland, and C.I. Brannan (1998). A mouse model for Prader-Willi syndrome imprinting center mutations. Nature Genetics 19, 25-31. PMID:9590284
• S. Lee and R. Wevrick (2000). Identification of novel imprinted transcripts in the Prader-Willi/Angelman syndrome deletion region: further evidence for regional imprinting control. Am. J. Human Genetics 66: 848-858. PMC1288168
• S. Lee, S. Kozlov, L. Hernandez, S.J. Chamberlain, C.I. Brannan, C.L. Stewart and R. Wevrick (2000). Expression and imprinting of MAGEL2 suggest a role in Prader-Willi Syndrome and the homologous murine imprinting phenotype. Human Molec Genetics 9, 1813-1819. PMID: 10915770
• S. Lee, C. Walker, B. Karten, S. L. Kuny, A.A. Tennese, M.A. O’Neill and R. Wevrick. (2005). Essential role for the Prader-Willi syndrome protein necdin in axonal outgrowth. Hum Molec. Genet 14, 627-637. PMID:15649943
2. My research group established several animal models for PWS and characterized their phenotypes, including mouse lines deficient in either Ndn (encoding necdin) or Magel2 (encoding the Magel2 protein). We identified phenotypes in these knockout mice that recapitulate many of the phenotypes described in people with Prader-Willi Syndrome.
• M. Gerard, L. Hernandez, R. Wevrick, and C.L. Stewart (1999). Disruption of the mouse Necdin gene results in early postnatal lethality: a model for neonatal distress in Prader-Willi syndrome. Nature Genetics, 23, 199-202. PMID: 10508517
• S. Koslov, J. W. Bogenpohl, M. P. Howell, R. Wevrick, S. Panda, J.B. Hogenesch, L. J. Muglia, R. Van Gelder, E. D. Herzog, C. L. Stewart (2007). The imprinted gene Magel2 regulates normal circadian output. Nature Genetics 39, 1266 - 1272. PMID: 17893678
• J.M. Bischof, C.L. Stewart, and R. Wevrick (2007). Inactivation of the mouse Magel2 gene results in growth abnormalities similar to Prader-Willi Syndrome. Hum. Molec. Genet. 16: 2713-19. PMID:17728320
• R. E. Mercer and R. Wevrick (2009). Loss of Magel2, a candidate gene for features of Prader-Willi syndrome, impairs reproductive function in mice. PLoS ONE 4(1): e4291. PMC2627930
• R. E. Mercer, E. M. Kwolek, J.M. Bischof, M. van Eede, R. M. Henkelman, and R. Wevrick (2009). Regionally reduced brain volume, altered serotonin neurochemistry, and abnormal behavior in mice null for the circadian rhythm output gene Magel2. Am. J. Med. Genetics B 150B: 1085–1099. PMID:19199291
• A. A. Tennese and R. Wevrick. (2011) Impaired hypothalamic regulation of endocrine function and delayed counter-regulatory response to hypoglycemia in Magel2-null mice. Endocrinology 152, 967-978. PMC:3198964
• R.E. Mercer, S.D. Michaelson, M.J.S. Chee, T.A. Atallah, R. Wevrick*, and W.F. Colmers* (2013) Magel2 Is Required for Leptin-Mediated Depolarization of POMC Neurons in the Hypothalamic Arcuate Nucleus in Mice PLoS Genetics, 9: e1003207. (*joint senior authors). PMC3547795
• J. L. Resnick, R. D. Nicholls, and R. Wevrick (2013) Recommendations for the investigation of animal models of Prader-Willi Syndrome. Mammalian Genome 24, 165-178. PMID:23609791
• W.F. Colmers and R. Wevrick (2013) Leptin signaling defects in Prader-Willi syndrome-an orphan obesity syndrome no more. Rare Diseases 1, e24421. (PMID: 25002992)
• I. Pravdivyi, K. Ballanyi, W.F. Colmers, R. Wevrick (2015) Progressive postnatal decline in leptin sensitivity of arcuate hypothalamic neurons in the Magel2-null mouse model of Prader-Willi Syndrome. Hum. Molec. Genet. 24, 4276-4283. PMID: 25926624
• 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.
• 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. (2016) Muscle dysfunction caused by loss of Magel2 in a mouse model of Prader-Willi and Schaaf-Yang syndromes. Hum Molec Genet. 25: 3798-3809. PMID: 27436578
• 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.
3. We have most recently investigated potential interventions for specific phenotypes using mice lacking Magel2 as a preclinical model for Prader-Willi (affected individuals have absence of Magel2, Ndn and other genes) and Schaaf-Yang (lacking Magel2 function) syndromes. This program is designed to shorten the intervals between basic discovery science and clinical trials, and between clinical trials and FDA approval and implementation in clinical practice, for both approved therapeutics (diazoxide, ketogenic diet, bariatric surgery), and investigational new drugs (e.g. Setmelanotide and three others currently under consideration for my program, targeting muscle mass, epigenetic modifications and the histamine system).
• D.M. Arble, J.W. Pressler, J. Sorrell, R. Wevrick, D.A. Sandoval. (2016) Sleeve gastrectomy leads to weight loss in the Magel2 knockout mouse. Surgery for Obesity and Related Diseases, S1550-7289, 30054-30055 PMID: 27396546.
• 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.
• I. Knani, B. J. Earley, S. Udi, A. Nemirovskai, R. Hadar, R. Cinar, H. J Hirsch, Y. Pollak, I. Gross, T. Eldar-Geva, D. P. Reyes-Capo, J. C. Han, A. M. Haqq, V. Gross-Tsur, R. Wevrick, and J. Tam. (2016) Targeting the Endocannabinoid/CB1 Receptor System for Treating Obesity in Prader-Willi Syndrome. Molecular Metabolism, 5: 1187–1199.
• 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.
The goal of my research program is to understand the genetic, molecular, and physiological basis of abnormal neurodevelopment, growth and metabolism using Prader-Willi syndrome mouse models. Specifically, we are investigating the Necdin and MAGEL2 genes, whose expression is disrupted in people with Prader-Willi syndrome. Both genes encode proteins of the “MAGE” (melanoma antigen) family that enhance the activity of RING E3 ubiquitin ligase complexes. I have studied the genetic basis of PWS since 1993, and discovered three of the genes whose expression is disrupted in this disorder. I have worked with mouse models of PWS since 1999, including two strains of mice null for the Necdin and Magel2 genes, respectively. Although my background is in medical and molecular genetics, I have developed expertise in metabolism, neuroscience, and endocrinology as part of our studies of these mouse models of PWS. Under my direction and with research grants from Canada’s federal funding agencies and from international charitable organizations, 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. I have a record of successful research projects that have led to highly cited publications relevant to the genetic, molecular, and physiological basis of both Prader-Willi syndrome and animal models of abnormal neurodevelopment. 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. Finally, our translational program aims to shorten the timeline between basic discovery and clinical implementation through the investigation of therapeutics in preclinical animal models of PWS.
Doctor of Philosophy
- University Of Toronto
Honors Bachelor of Sciences
- Queen's University