Centre for Brain and Behaviour Staff Profiles
Each month the Centre for Brain and Behaviour will profile two of its members.
This month, we are profiling Dr. Elizabeth Kerr and Dr. Berge Minassian.
Elizabeth Kerr, PhD
Dr. Elizabeth Kerr was awarded her B.A.Sc. from the University of Guelph, her M.A. from Lakehead University, and Ph.D. from the University of Calgary, following which she completed a CPA/APA accredited internship in Neuropsychology at the Children’s Hospital of Western Ontario. She has been a clinical neuropsychologist at SickKids since 1995, holds an associate scientific appointment in the Division of Neurology, SickKids and an adjunct clinical academic appointment with the Department of Paediatrics, the University of Toronto.
As a full time clinician, Dr. Kerr heads up the Epilepsy Classroom and provides neuropsychological assessment and consultation to the Epilepsy Classroom, the Epilepsy Surgery program and Metabolic Genetics. Her major research activities focus on neurocognitive and behavioural outcomes in medically intractable epilepsy and genetic conditions:
1. Neurocognitive and behavioural functioning in children treated for intractable epilepsy. Several projects have been initiated in this area, including (a) evaluating the effectiveness of a specialized learning environment in terms of academic gains and social competence (Principal Investigator: Dr. E. Kerr), (b) examining health outcomes and activities of daily living (Dr. E. Kerr with N. Fayed), the aim of which is to learn the best measure to assess potential difficulties and thereby assist clinicians and researchers determine the best way to help children acquire these skills so that they can be more independent, and (c) understanding language lateralization (Principal Investigators: D. Kadis & Dr. M.L. Smith)
2. Neurodevelopment in Shwachman Diamond Syndrome (SDS) (Principal Investigator: Dr. E. Kerr). This study, with colleagues L. Ellis, and Drs. P. Durie, J. Rommens, and A. Dupuis, is the first comprehensive characterization of the neuropsychological performance of a population-based sample of genotypically and phenotypically defined children with SDS. Results indicate neurocognitive dysfunction with loss of SBDS, the gene responsible for the syndrome. A clear finding is that these children require early assessment, monitoring and remedial assistance. Future investigations will include neuroimaging
3. Genetics of reading disabilities (Principal Investigator: Dr. C. Barr; Co-Investigators: Dr. M. Lovett & Dr. E. Kerr). The overall aim of this area of research is to identify genes that contribute to the development of reading disabilities and determine how genetic variation contributes to the risk of the development of reading disabilities as well as to the cognitive processes underlying reading and related phenotypes.
4. Understanding executive skills and social skills in Phenylketonuria (PKU) (Principal Investigator: Dr. E. Kerr; Co-investigator: Dr. E. Mamak). This study explores the frequency of, and the relationship between, executive and social functions in adolescents with PKU, an inborn error of metabolism. Additionally, the associations between areas of concern and metabolic control as well as cognitive functioning will be examined.
5. Atypical Cystic Fibrosis (CF) (Principal Investigator: Dr. E. Kerr). The final stages of a study designed to understand the psychological impact of delivering ambiguous or uncertain diagnostic information to adults being investigated for possible CF are being completed. The study is an integral part of a concurrent CF study (Drs. P. Durie & E. Tullis) that is examining and re-establishing the diagnostic criteria for CF disease. Although CF is typically diagnosed in childhood, with thousands of mutations of the CFTR gene being found, the diagnosis of milder forms of CF is now being made in adulthood. This study has direct relevance for mediating adaptation.
Dr. Kerr’s research has received funding from external agencies including the Canadian Institute of Health Research, The National Institute of Health, The Sanfilippo Children’s Research Foundation, Shwachman – Diamond Syndrome Support International and the Garrod Society.
Recent Publications:
Kerr EN, Ellis L, Dupuis A, Rommens JM, Durie PR: The behavioral phenotype of school-age children with Shwachman Diamond Syndrome indicates neurocognitive dysfunction with loss of SBDS. Submitted for publication.
Fayed N, Kerr EN: Comparing quality of life scales in childhood epilepsy: What’s in the measures? International Journal of Disability, Community and Rehabilitation. Accepted for publication.
Fayed N, Kerr EN: Identifying occupational issues among children with intractable epilepsy: Individualized versus norm-referenced approaches. Canadian Journal of Occupational Therapy 2009: 76(2): pp 90-97.
Kadis DS, Kerr EN, Rutka JT, Snead III OC, Weiss SK, Smith ML: Pathology type does not predict language lateralization in children with medically intractable epilepsy. Epilepsia: Electronically published Feb 2009 ahead of print.
Couto JM, Gomez L, Wigg K, Cate-Carter T, Archibald J, Anderson B, Tannock R, Kerr EN, Lovett MW, Humphries T, Barr CL: The KIAA0319-Like (KIAA0319l) gene on chromosome 1p34 as a candidate for reading disabilities. Journal of Neurogenetics 2008: 22(4): pp 295-313.
Kadis DS, Iida K, Kerr EN, Logan WJ, McAndrews MP, Ochi A, Otsubo H, Rutka JT, Snead OC, Weiss SK, Smith ML: Intrahemispheric reorganization of language in children with medically intractable epilepsy of the left hemisphere. Journal of the International Neuropsychological Society 2007: 13: pp 505-516.
Dupuis LL, Taddio AT, Kerr EN, Kelly A, MacKeigan L: Development and validation of the Pediatric Nausea Assessment Tool for use in children receiving antineoplastic agents. Pharmacotherapy 2006: 26(9): pp 1221-1231.
Berge Minassian, MD, FRCPC
Dr. Minassian graduated from McGill Medical School in Montreal, trained in adult neurology at the University of California, Los Angeles and in paediatric epileptology at the Hospital for Sick Children, Toronto. Dr. Minassian spends 80 per cent of his time in the laboratory to help further knowledge in his areas of specialty and design better treatments.
Rare diseases are rare because they are severe. Rare disease genes therefore have a major impact on the body, and identifying these genes leads to insights into functions that are of major importance.
Dr. Minassian has focused his attention on several rare diseases. He discovered the causative genetic defects in two forms of Progressive Myoclonus Epilepsy (Lafora disease), an untreatable and fatal form of epilepsy that afflicts previously normal children and leads to their death (Nature Genetics 1998 and 2003). Dr. Minassian is now using the information from the genes to gradually understand the cellular and molecular pathways affected in these diseases. In particular, his group is uncovering a new level of control of glycogen metabolism in the brain, which when disturbed, results in hyperphosporylation, deposition and accumulation of glycogen, which first disturbs cell function and then leads to cell death.
Dr. Minassian has also uncovered the causative defect in a form of Muscular Dystrophy, X-linked Myopathy with Excessive Autophagy. His group has shown that this disease is caused by mutations of VMA21, the chaperone that assembles the cell's acid pumps (V-ATPases). The reduction in V-ATPases results in decreased acidification of lysosomes, which leads to an arrest of autophagy, the process of cell content recycling. This results in massive accumulations of cell contents that cannot be recycled and death of skeletal muscle fibers (Cell, 2009).
Presently, Dr. Minassian's team is chasing the causative gene defect in a rare disease characterized by infantile onset Parkinsonism.
Common diseases are important because they are common. Dr. Minassian has made important contributions to common neurogenetic conditions such as Angelman Syndrome (Annals of Neurology, 1998) and Rett Syndrome (Nature Genetics 2004). He also collaborates in large studies aimed at identifying common human epilepsy genes. Finally, Dr. Minassian initiated a program to identify human epilepsy genes by first identifying them in dogs, using saliva as a source of DNA. His group identified the first canine epilepsy gene (Science, 2005) and is now mapping several others.
Recent Publications:
Ramachandran N, Munteanu I, Wang P, Aubourg P, Rilstone JJ, Israelian N, Naranian T. Paroutis P, Guo R, Ren ZP, Nishino I, Chabrol B, Pellissier JF, Minetti C, Udd B, Fardeau M, Tailor CS, Mahuran DJ, Kissel JT, Levy N, Manolson MF, Ackerley CA, Minassian BA: VMA21 deficiency causes an autophagic myopathy by compromising V-ATPase activity and lysosomal acidification. Cell 2009: 137(2): pp 235-246.
Striano P, Zara F, Turnbull J, Girard JM, Ackerley CA, Cervasio M, DeRosa G, Del Basso-DeCaro ML, Striano S, Minassian BA: Typical progression of myoclonic epilepsy of the Lafora type: A case report. Nature Clinical Practice. Neurology 2008: 4(2): pp 106-111.
Turnbull J, Kumar S, Ren ZP, Muralithara S, Naranian T, Ackerley CA, Minassian BA: Lafora progressive myoclonus epilepy: Disease course homogeneity in a genetic isolate. Jpurnal of Child Neurology 2008: 23(2): pp 240-242.
Santoshkumar B, Turnbull J, Minassian BA: Unverricht-Lundborg progressive myoclonus epilepsy in Oman. Pediatric Neurology 2008: 38(4): pp 252-255.
Zhang Y, Minassian BA: WIll my Rett syndrome patient walk, talk and use her hands? Neurology 2008: 70(16): pp 1302-1303.
Ackerley CA, Ramachandran N, Munteanu I, Kalima H, Minassian BA: Thrombocytopathy and Leukocytopathy in X-linked myopathy with excessive autophagy. Microscopy and Microanalysis 2008: 14(Sup 2): pp 1524-1525.
Munteanu I, Ramachandran N, Mnatzakanian GN, Villanova M. Fardeau M. Levy N. Kissel JT, Minassian BA: Fine-mapping the gene for X-linked myopathy with excessive autophagy. Neurology 2008: 71(12): pp 951-953.
Liu R, Wang L, Chen C, Liu Y, Zhou P, Wang Y, Wang X, Turnbull J, Minassian BA, Liu Y, Zheng P: Laforin negatively regulates cell cycle progression through GSK-3 beta dependent mechanisms. Molecular Cellular Biology 2008: 28(33): pp 7236-7244.
Tagliabracci VS, Girard JM, Segvich D, Meyer C, Turnbull J, Zhao X, Minassian BA, Depaoli-Roach AA, Roach PJ: Abnormal metabolism of glycogen phosphate as a cause for Lafora disease. Journal of Biological Chemistry 2008: 283(49): pp 33816-33825.
Links to full articles:
Mutations in NHLRC1 cause progressive myoclonus