Stephen Meyn, MD, PhD, FRCPC, FACMG
The Hospital for Sick Children
Staff Geneticist
Cancer Genetics Program
Research Institute
Head & Senior Scientist
Genetics & Genome Biology
University of Toronto
Molecular & Medical Genetics, Paediatrics
Professor
Phone: 416-813-8485
Fax: 416-813-4931
e-mail: stephen.meyn@sickkids.ca
Research Interests
- The Chromosome Instability Syndromes (Ataxia-Telangiectasia, Fanconi anaemia, Bloom syndrome, Nijmegen breakage syndrome, Werner syndrome)
- Cancer Genetics
- Genetics of Aging
- DNA Repair and Genetic Recombination
Research Activities
The ability to maintain genomic integrity in the face of DNA damage is critical for survival of the individual cell, the organism and the species. The means by which mammalian cells achieve this goal are complex and involve DNA repair, genetic recombination, alterations in the cell cycle and programmed cell death. As a medical geneticist, my approach to understanding these cellular defenses is to study the molecular pathology of the chromosome instability syndromes, a group of cancer-prone human diseases in which these protective mechanisms are disrupted.
Our research program is divided into three areas that are designed to shed light on how cells respond to that DNA damage that occurs normally (e.g., meiosis) and that which is created in pathologic situations (e.g., telomere shortening in aging cells and exposure to exogenous mutagens). We are currently studying:
- The roles that the chromosome instability syndrome proteins and their protein partners play in meiosis in human and mouse germ cells.
- The in vivo interactions between chromosome instability syndrome proteins and damaged DNA in human cells using laser micro-irradiation and fluorescence microscopy.
- The involvement of chromosome
Publications
Bradshaw PS, Stavropoulos DJ, Meyn MS. Human telomeric protein TRF2 associates with genomic double-strand breaks as an early response to DNA damage. Nature Genetics 37: 193-198, 2005.
Wong JC, Alon N, Mckerlie C, Huang JR, Meyn MS, Buchwald M. Targeted disruption of exons 1 to 6 of the Fanconi Anemia group A gene leads to growth retardation, strain-specific microphthalmia, meiotic defects and primordial germ cell hypoplasia. Human Molecular Genetics 12: 2053-2076, 2003.
Houghtaling S, Timmers C, Noll M, Finegold MJ, Jones SN, Meyn MS, Grompe M. Epithelial cancer in Fanconi anemia complementation group D2 (Fancd2) knockout mice. Genes & Development 17:2021-2035, 2003.
Stavropoulos DJ, Bradshaw PS, Li X. Pasic I, Truong K, Ikura M, Ungrin M, Meyn MS. The Bloom syndrome helicase BLM interacts with TRF2 at telomeres in ALT cells and promotes telomere lengthening. Hum Mol Genet 11: pp 3135-3144, 2002.
Kolomietz E, Meyn MS, Pandita A, Squire JA: The role of Alu repeat clusters as mediators of recurrent chromosomal aberrations in tumors. Genes, Chromo. Cancer 35: pp 97-112, 2002.
Clarkson B, Pavenski K, Dupuis L, Kennedy S. Meyn S, Nezarati MM, Nie G, Weksberg R, Withers S, Quercia N, Teebi AS, Teshima I: Detecting rearrangements in children using subtelomeric FISH and SKY. American Journal of Medical Genetics 107: pp 267-274, 2002.
Garcia-Higuera I, Taniguchi T, Ganesan S, Meyn MS, Timmers C, Grompe M, D'Andrea AD. DNA Damage-Induced Association of the Fanconi Anemia Protein, FANCD2, with BRCA1 Nuclear Foci. Molec. Cell 7: 249-262, 2001.
Fritz E, Friedl AA, Eckardt-Schupp F, Meyn MS. The yeast TEL1 gene partially substitutes for human ATM in suppressing hyper-recombination, radiation-induced apoptosis and telomere shortening in A-T cells. Mol. Biol. Cell 11: 2605-2616, 2000.
Hisama FM, Chen Y-H, Meyn MS, Oshima J, Weissman SH. Expression of telomerase or WRN reverses the 4NQO sensitivity of Werner syndrome fibroblasts. Cancer Research 60: 2372-2376, 2000.
Meyn MS. Ataxia-telangiectasia, cancer and the ATM gene. Clin. Genet. 55: 289-304, 1999.
Fritz E, Elsea SH, Patel PI, Meyn MS. Overexpression of a human topoisomerase III protein alleviates multiple aspects of the ataxia-telangiectasia phenotype. Proc. Natl. Acad. Sci. USA 94: 4538-4542, 1997.
Keegan KS, Holtzman DA, Plug AW, Brainerd EE, Christenson ER, Bentley Taylor EM, Meyn MS, Moss SB, Carr AM, Ashley T, Hoekstra M. The ATR and ATM protein kinases associate with different sites along meiotically pairing chromosomes. Genes & Development 10: 2423-2437, 1996.
Xu Y, Bronson RT, Brainerd EE, Ashley T, Meyn MS, Baltimore D. Targeted disruption of Atm leads to g-rowth retardation, chromosomal fragmentation during meiosis, immune defects and thymic lymphoma. Genes & Development 10: 2211-2422, 1996.
Meyn MS. High spontaneous intrachromosomal recombination rates in ataxia-telangiectasia. Science 260: 1327-1330, 1993.