Zoha Kibar, Ph.D.

Zoha Kibar is assistant professor in the Department of Obstetrics and Gynaecology at the Université de Montréal. Her laboratory is at the CHU Sainte-Justine Research Centre.

CONTACT

CHU Sainte-Justine Research Centre
3175 Cote-Ste-Catherine,
Room A711
Montreal, Quebec
Canada H3T 1C5
Phone: 514-345-4931, extension 3984
Fax: 514-345 4698
Email :zoha.kibar@recherche-ste-justine.qc.ca

RÉSUMÉ DES ACTIVITÉS DE RECHERCHE

Our research uses genetics, genomics and molecular biology to identify and understand the molecular basis of abnormalities in the dorsomedial structures of the central and skeletal nervous systems, particularly neural tube defects (NTDs) and Chiari I malformation (CMI). These abnormalities, quite common in humans, are of a multifactorial origin involving both genetic and environmental factors that remain largely unknown.

NTDs, including spina bifida and anencephaly are congenital malformations where the neural tube fails to close. During my postdoctoral studies at McGill University, I identified the mutated gene in the Loop-tail (Lp) mouse, a well-established model for the study of NTDs in humans. This gene, designated as Vangl2, is part of the non-canonical Frizzled (Fz)/Dishevelled (Dvl) signalling pathway controlling the morphogenetic processes central to neural tube closure. We have since identified three pathogenic mutations in a human homolog called VANGL1, in patients with NTDs. The objectives of our research project are: (1) molecular genetic analysis of other members of the non-canonical Fz/Dvl signalling pathway in human NTDs, (2) molecular genetic studies of other mouse models generated by the N-ethyl-N-nitrosourea mutagenic agent and (3) analysis of copy number variants in the genome of NTD patients using array-based Comparative Genomic Hybridization.

CMI is a common abnormality at the craniocervical junction characterized by a descent of the cerebellar tonsils through the foramen magnum and into the spinal canal. CMI in humans is similar to a hereditary disease common in two dog breeds, the Cavalier King Charles Spaniel and the Brussels Griffon. The main objective of this project is to identify and characterize the genes predisposing to CMI in the dog model, as a starting point for parallel studies of orthologous genes in humans.

STUDIED DISEASES

Neural tube defects (NTDs) and Chiari I malformation (CMI). Our studies of NTDs and CMI will help us gain understanding of the molecular and cellular mechanisms underlying the pathogenesis of these abnormalities. The studies are essential in characterizing gene-environment interactions with which it will be possible to develop new prevention strategies and improved genetic counselling for at-risk couples.

SELECTED PUBLICATIONS

Z. Kibar, V. Capra and P. Gros (2007). Toward understanding the genetic basis of neural tube defects. Clin. Genet., 71, 295-310 .

Z. Kibar, E. Torban, J. R. McDearmid, A. Reynolds, J. Berghout, M. Mathieu, I. Kirillova, P. De Marco, E. Merello, J. M. Hayes, J. B. Wallingford, P. Drapeau, V. Capra, and P. Gros (2007). Mutations in VANGL1 associated with neural tube defects in humans. N. Engl J Med., 356, 1432-1437.

Z. Kibar, S. Gauthier, S-H. Lee, S. Vidal and P. Gros (2003). Rescue of the neural tube defect of Loop-tail mice by a BAC clone containing the Ltap gene. Genomics, 82, 397-400.

Z. Kibar, K. J. Vogan, N. Groulx, M. J. Justice, D. A. Underhill and P. Gros (2001). Ltap, a mammalian homolog of Drosophila Strabismus/Van Gogh, is altered in the mouse neural tube mutant Loop-tail. Nature Genet., 28, 251-255.

Z. Kibar, D. A. Underhill, F. Canonne-Hergaux, S. Gauthier, M. J. Justice and P. Gros (2001). Identification of a new chemically induced allele (Lpm1Jus) at the loop-tail locus: morphology, histology, and genetic mapping. Genomics, 72, 331-337.

J. Lamartine, G. M. Essenfelder, Z. Kibar, I. Lanneluc, E. Callouet, D. Laoudj, G. Lemaître, C. Hand, S. J. Haytfick, J. Zonana, S. Antonorakis, D. P. Kelsell, A. L. Christianson, A. Pitaval, V. Der Kaloustian, C. Blanchet-Bardon, G. A. Rouleau and G. Waksman (2000). Mutations in the human-connexin gene GJB6 cause hidrotic ectodermal dysplasia (Clouston syndrome). Nature Genet., 26, 142-144.

Z. Kibar, M.-P. Dubé, J. Powell, C. McCuaïg, S. Hayflick, J. Zonana, A. Hovnanian, U. Radhakrishna, S. E. Antonarakis, A. Benohanian, A. D. Sheeran, M.L. Stephan, R. Gosselin, D. P. Kelsell, A. L. Christianson, F. C. Fraser, V. M. Der Kaloustian and G. A. Rouleau (2000). Clouston hidrotic ectodermal dysplasia (HED): genetic homogeneity, presence of a founder effect in the French Canadian population and fine genetic mapping. Eur. J. Hum. Genet., 8, 372-380.

USEFUL LINKS

CHU Ste-Justine Research Centre

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