• Genetics & Molecular Biology

    Genetics & Molecular Biology

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All courses for every first-year Science student will be delivered online this fall. A limited number of students in their second, third and fourth years will return to campus for part of the semester.

Molecular Biology is a fundamental area of investigative research in Biology that employs new technologies and experimental approaches to examine fundamental processes in all living organisms. In the course of these investigations, we use wide variety of model organisms, including mice, guinea pigs, human tissue cell cultures, the nematode species Caenorhabditis elegans, the plant Arabidopsis thaliana, model bacteria and the fruit fly Drosophila melanogaster. The research is of immediate relevance to human health in many areas including cancer, inherited genetic diseases and disease resistance, DNA repair, and neurosystem development and function. We welcome strong applicants as undergraduate researchers, graduate students and postdoctoral fellows.

Suleiman Igdoura
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Professor
LSB 335
(905) 525-9140 ext. 27729
...

Molecular Genetics ofTay-Sachs disease and Sialidosis. My research focuses on the molecular genetics of two diseases, Tay-Sachs and sialidosis, which are lysosomal storage disorders caused by defects in ?-hexosaminidase A and sialidase respectively. The lysosomal storage process begins in the fetus early in pregnancy but most of these diseases become clinically evident within the first 2 years or have a later onset. The majority of patients show a fatal course with progressive involvement of the nervous system. We have focused on identifying disease-causing mutations in order to determine the impact of these mutations on disease phenotype. This provides informative genotype/phenotype correlations and a precise understanding of the structure/function of the enzymes. With the discovery of more mutant alleles, we have utilized this DNA-based technology to complement the enzyme-based prenatal diagnostic procedures. We are also developing mouse models of Tay-Sachs disease and sialidosis which will allow us to study the pathophysiology of the diseases in order to test potential therapeutic strategies in vivo. Finally, we are developing recombinant adenovirus vectors coding for the human sialidase gene for therapeutic applications. Adenoviral vectors represent a new class of biotherapeutics and its development for gene therapy holds much hope for patients.

Genetics & Molecular Biology

  • White EJ, Trigatti BL, and SA. Igdoura. 2017. Suppression of NK and CD8+ T cells reduces astrogliosis but accelerates cerebellar dysfunction and shortens life span in a mouse model of Sandhoff. Journal of Neuroimmunology. 306:55-67.
  • Igdoura SA. 2017. Asialoglycoprotein receptors as important mediators of plasma lipids and atherosclerosis. Current Opinion in Lipidology. 28(2):209-212.
  • Hooper AWM, Alamilla JF, Venier* RE, Gillespie DC, and Igdoura SA. 2017. Neuronal Pentraxin 1 depletion delays neurodegeneration and extends life in Sandhoff disease mice. Human Molecular Genetics 26(4):661-673.
  • Hooper AWM and SA Igdoura. 2016. Bi-phasic gliosis drives neuropathology in a Sandhoff disease mouse model. Journal of Neuroimmunology. 299:19-27.
  • Lhoták Š, Gyulay G, Cutz JC, Al-Hashimi A, Trigatti B, Richards C, Igdoura SA, Steinberg G, Bramson J, Ask K, and Austin R. 2016. Characterization of Proliferating Lesion-Resident Cells during All Stages of Atherosclerotic Growth. Journal of the American Heart Association (JAHA). 5 (8): e003945.
  • Fuller M, Dadoo O, Serkis V, Abutouk D, MacDonald M, Igdoura SA and Trigatti BL. 2014. The effects of diet on occlusive coronary artery atherosclerosis, thrombosis and myocardial infarction in SR-BI/LDL receptor Double KO mice. Arterioscler Thromb Vasc Biol. 34(11):2394-403.
  • Pei Y, Chen X, Aboutouk D, Fuller MT, Dadoo O, Yu P, White EJ, Igdoura SA, Trigatti BL. 2013. SR-BI in bone marrow derived cells protects mice from diet induced coronary artery atherosclerosis and myocardial infarction. PLoS One. 8: e72492.
  • Abo-Ouf H, Hooper AW, White EJ, van Rensburg HJ, Trigatti BL, and SA Igdoura. 2013. Deletion of tumor necrosis factor-α ameliorates neurodegeneration in Sandhoff disease mice. Hum. Mol. Genet. 22: 3960-75.
  • Al-Jarallah A, Igdoura F, Zhang Y, Tenedero CB, White EJ, MacDonald ME, Igdoura SA, Trigatti BL. 2013. The effect of pomegranate extract on coronary artery atherosclerosis in SR-BI/APOE double knockout mice. Atheroschlerosis. 228: 80-89.
  • Yang A, Gyulay G, Mitchell M, White E, Trigatti BL and SA Igdoura. 2012. Hypomorphic Sialidase expression decreases serum cholesterol by down-regulation of VLDL production in Mice. J. Lipid Res. 53:2573-85
  • Venier R and SA Igdoura. 2012. Miglustat as a therapeutic agent: prospects and caveats. J. Med. Genet. 49(9):591-7.
  • O'Leary E and SA Igdoura. 2012. The therapeutic potential of pharmacological chaperones and proteosomal inhibitors, Celastrol and MG132 in the treatment of Sialidosis. Mol. Genet. and Metab. 107(1-2):173-185.
  • Champigny M, Mitchell M, Fox-Robichaud A, Trigatti BL and SA Igdoura. 2009. A point mutation in the neu1 promoter recruits an ectopic repressor, Nkx3.2 and results in a mouse model of sialidase deficiency. Mol. Genet. and Metab.  97(1):43-52.
  • Luedtke CC, Andonian S, Igdoura S, Hermo L. Cathepsin A is expressed in a cell- and region-specific manner in the testis and epididymis and is not regulated by testicular or pituitary factors. J Histochem Cytochem. 2000 ; 48(8):1131-46.   Abstract
  • Lefrancois S, Michaud L, Potier M, Igdoura S, Morales CR. Role of sphingolipids in the transport of prosaposin to the lysosomes. J Lipid Res.1999; 40(9):1593-603.   Abstract
  • Igdoura SA, Herscovics A, Lal A, Moremen KW, Morales CR, Hermo L. a -mannosidases involved in N-glycan processing show cell specificity and distinct subcompartmentalization within the Golgi apparatus of cells in the testis and epididymis. Eur J Cell Biol. 1999;78(7):441-52.    Abstract
  • Igdoura SA, Mertineit C, Trasler JM, Gravel RA. Sialidase-mediated depletion of GM2 ganglioside in Tay-Sachs neuroglia cells. Hum Mol Genet. 1999; 8(6):1111-6.   Abstract
  • Igdoura SA, Gafuik C, Mertineit C, Saberi F, Pshezhetsky AV, Potier M, Trasler JM, Gravel RA. Cloning of the cDNA and gene encoding mouse lysosomal sialidase and correction of sialidase deficiency in human sialidosis and mouse SM/J fibroblasts. Hum Mol Genet. 1998; 7(1):115-21.  Abstract
  • Huang JQ, Trasler JM, Igdoura S, Michaud J, Hanal N, Gravel RA. Apoptotic cell death in mouse models of GM2 gangliosidosis and observations on human Tay-Sachs and Sandhoff diseases. Hum Mol Genet. 1997; 6(11):1879-85. Abstract
  • Igdoura SA, Argraves WS, Morales CR. Low density lipoprotein receptor-related protein-1 expression in the testis: regulated expression in Sertoli cells. J Androl. 1997; 18(4):400-10. Abstract
  • Pshezhetsky AV, Richard C, Michaud L, Igdoura S, Wang S, Elsliger MA, Qu J, Leclerc D, Gravel R, Dallaire L, Potier M. Cloning, expression and chromosomal mapping of human lysosomal sialidase and characterization of mutations in sialidosis. Nature Genet. 1997; 15(3):316-20. Abstract
  • Morales CR, Igdoura SA, Wosu UA, Boman J, Argraves WS. Low density lipoprotein receptor-related protein-2 expression in efferent duct and epididymal epithelia: evidence in rats for its in vivo role in endocytosis of apolipoprotein J/clusterin. Biol Reprod. 1996; 55(3):676-83. Abstract
  • Burke J, Lipari F, Igdoura S, Herscovics A. The Saccharomyces cerevisiae processing alpha 1,2-mannosidase is localized in the endoplasmic reticulum, independently of known retrieval motifs. Eur J Cell Biol. 1996; 70(4):298-305. Abstract
  • Igdoura SA, Rasky A, Morales CR. Trafficking of sulfated glycoprotein-1 (prosaposin) to lysosomes or to the extracellular space in rat Sertoli cells.Cell Tissue Res. 1996; 283(3):385-94. Abstract
  • Phaneuf D, Wakamatsu N, Huang JQ, Borowski A, Peterson AC, Fortunato SR, Ritter G, Igdoura SA, Morales CR, Benoit G, Akerman BR, Leclerc D, Hanai N, Marth JD, Trasler JM, Gravel RA. Dramatically different phenotypes in mouse models of human Tay-Sachs and Sandhoff diseases. Hum Mol Genet. 1996; 5(1):1-14. Abstract
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