Manitoba Institute of Cell Biology
University of Manitoba, Winnipeg
Telephone: +1 204-7872135
Fax: +1 204-7873125
Principal areas of expertise: Molecular biology and genetics; Genome instability; Bioinformatics
♦ Mechanisms of genome instability and three-dimensional nuclear organization of the mammalian genome
Professor Mai’s research focuses on mechanisms of c-Myc-dependent locus-specific and karyotypic instability, c-Myc-dependent tumour development in vivo and on understanding the three-dimensional (3D) nuclear organization of the mammalian genome in normal, immortalized and tumour cells.
One of the major achievements of the c-Myc research line was the first demonstration that the deregulated expression of the proto-oncogene induces dynamic karyotypic alterations and mediates rearrangements, chromosomal and extrachromosomal amplification of specific genes. Using the mouse model of plasmacytoma the critical region of chromosome 11 involved in the promotion of accelerated plasmacytoma development was identified. Studying the three-dimensional (3D) nuclear organization of the mammalian genome, prof Mai demonstrated the existence of specific 3D signatures that are significantly different in normal, immortalized and tumor cell nuclei. In collaboration with Dr. Yuval Garini (then at Delft University of Technology, now at Bar Ilan University, Israel) a software [TeloViewTM] enabling the measurements the 3D nuclear organization of telomeres was set up. Using TeloViewTM Hodgkin’s patients were stratified into responding and non-responding groups. Ongoing studies focus on Hodgkin’s lymphoma, multiple myeloma, monoclonal gammopathies with unknown significance, myelodisplatic syndrome and acute myeloid leukemia, chronic lymphocytic leukemia, and various solid tumours. The current research is aimed to introduce the 3D telomeric signatures as a clinical tool for cancer diagnosis, cancer cell detection, treatment decisions and monitoring. Recent studies done in collaboration with Dr. Angela Garcia (Queens University, Kingston) have described 3D nuclear telomeric profiles that specifically characterize patients with Alzheimer’s diseases. Such profiles are different from 3D profiles found in age- and sex-matched healthy controls.
Mathur S, Glogowska A, McAvoy E, Righolt C, Rutherford C, Willing C, Banik U, Ruthirakuban M, Mai S, Garcia A (2013) Three-dimensional quantitative imaging of telomeres in buccal cells identifies mild, moderate and severe Alzheimer patients. J Alzheimers Dis, doi: 10 3233/JAD-130866
Knecht H, Kongruttanachok N, Sawan B, Brossard J, Prevost S, Turcotte E, Lichtensztejn Z, Lichtensztejn D, Mai S (2012) 3D telomere signatures of Hodgkin- and Reed-Sternberg cells at diagnosis indicate refractory/relapsing Hodgkin’s lymphoma. Transl Oncol 5: 269-277
Kuzyk A, Mai S (2012) Selected telomere length changes and aberrant 3D nuclear telomere organization during fast-onset mouse plasmacytomas. Neoplasia 14: 344-351
Gadji M, Awe JA, Rodrigues P, Kumar R, Houston D, Falcão PR, de Oliveira FM, Mai S (2012) Profiling the three-dimensional nuclear telomeric architecture in myelodysplastic syndrome and acute myeloid leukemia defines patient subpopulations. Clin Cancer Res 18: 3293-3304
Rio Frio T, Lavoie J, Hamel N, Geyer FC, Kushner YB, Novak DJ, Wark L, Capelli C, Reis-Filho JS, Mai S, Pastinen T, Tischkowitz MD, Marcus VA, Foulkes WD (2010) Homozygous BUB1B Mutation and Susceptibility to Gastrointestinal Neoplasia. N Engl J Med 363: 2628-2637
Guffei A, Sarkar R, Klewes R, Righolt C, Knecht H, Mai S (2010) Dynamic chromosomal rearrangements in Hodgkin’s lymphoma are due to ongoing 3D nuclear remodeling and breakage-bridge-fusions. Haematologica 95: 2038-2046
Lacoste S, Wiechec E, Williams G, Henriksson M, Klein G, Mai S (2009) Chromosomal rearrangements after ex-vivo Epstein-Barr virus (EBV) infection of human B cells. Oncogene 29: 503-515