|Professor Physiology, Biochemistry & Medical Genetics, Human Anatomy and Cell Science
Director of The Genomic Centre for Cancer Research and Diagnosis (GCCRD)
B.Sc. in Biology, Univ. of Cologne, Germany, 1981
M.Sc. in Biology, French & Pedogogics, Univ. of Cologne, Germany, 1985
Ph. D. in Molecular Biology, Univ of Karlsruhe, Germany, 1991
6046-675 McDermot Ave
Winnipeg, Mb R3E 0V9
Email: Dr Sabine Mai PhD
ResearchDr. Mai's research focuses on mechanisms of c-Myc-dependent locus-specific and karyotypic instability, c-Myc-dependent tumour development in vivo (using the mouse model of plasmacytoma) and on understanding the three-dimensional (3D) nuclear organization of the mammalian genome in normal, immortalized and tumour cells.
- c-Myc-dependent locus-specific and karyotypic instability.
- c-Myc-dependent tumour development in vivo.
- The three-dimensional (3D) nuclear organization of the mammalian genome in normal, immortalized and tumour cells.
We were the first to demonstrate that the deregulated expression of the proto-oncogene c-Myc induces dynamic karyotypic alterations (Mai et al., 1996a), and mediates rearrangements, chromosomal and extrachromosomal amplification of specific genes. Among these genes are dihydrofolate reductase (DHFR), (Mai, 1994; Mai et al., 1996b), CCND2 (cyclin D2) (Mai et al., 1999), ribonucleotide reductase R2 (R2) (Kuschak et al., 1999), and the carbamoyl-phosphate synthetase-aspartate transcarbamoyl-dihydroorotase (CAD) (Fukasawa et al., 1997) gene. Other genes, such as syndecan-1 and 2, glyceraldehyde-3-phosphate-dehydrogenase, ribonucleotide reductase R1, and cyclin C, remain unaffected irrespective of c-Myc protein levels (Mai et al., 1996b). c-Myc-dependent illegitimate locus-specific de novo replication initiation induces R2 gene amplification (Kuschak et al., 2002). An additional mechanism of c-Myc activation involves c-Myc transcription from extrachromosomal elements (Wiener et al., 1999). Analyses into the functions of EEs have demonstrated that they carry modified histones and are transcriptional competent. Furthermore, they are able to replicate their DNA (Smith et al., 2002). c-Myc-induced EEs therefore are functional mini-chromosomes with the ability to actively contribute to cellular transformation.
Mouse plasmacytomas (PCTs) develop in susceptible mice. The traditional model uses pristane as inducing agent, and all PCTs that develop subsequently display the constitutive deregulation of c-Myc due to its translocation to one of the immunoglobulin (Ig) loci. The c-myc/IgH translocation is the most frequent one in pristane-induced plasmacytomas of BALB/c mice (Potter and Wiener, 1992). Pristane-induced PCTs develop over a long latency period (up to 300 days). If pristane is combined with v-abl or with v-abl/myc, the latency periods drop significantly (Potter and Wiener, 1992). Such short latency tumours develop within 45 days after v-abl/myc and display chromosomal aberrations of chromosome 11. We have identified the critical region of chromosome 11 involved in the promotion of accelerated plasmacytoma development (Wiener et al., 2010). This region is chromosome 11 cytoband 11E2, and it is syntenic to human 17q25 and rat 10q32. The evolutionarily conserved region undergoes frequent rearrangements in lymphoid and non-lymphoid tumours of all three species.
We examine the spatial organization of telomeres, centromeres and chromosomes and obtain specific 3D signatures that are significantly different in normal, immortalized and tumour cell nuclei. In collaboration with Dr. Yuval Garini (then at Delft University of Technology, now at Bar Ilan University, Israel), we developed software [TeloViewTM] that enabled the measurements the 3D nuclear organization of telomeres (Vermolen et al., 2005). This program has allowed us to determine significant differences between normal and tumour cells (Mai and Garini, 2005), after c-Myc deregulation (Louis et al., 2005; Mai and Garini, 2005), after Epstein-Barr virus-infection (Lacoste et al., 2010), during the transition of mono-nucleated to multi-nucleated Hodgkin cells (Knecht et al., 2009), in glioblastoma (Gadji et al., 2010), myelodysplastic syndromes and acute myeloid leukemia (Gadji et al., 2012). We have automated TeloViewTM and use the automated version, TeloScan (Gadji et al., 2010; Klewes et al., 2011). Ongoing studies focus on Hodgkin's lymphoma (with and without recurrent disease), multiple myeloma, monoclonal gammopathies with unknown significance, myelodisplatic syndrome and acute myeloid leukemia, chronic lymphocytic leukemia, ependymoma, breast and thyroid cancer as well as esophageal cancer and cholangiocarcinoma. In summary, the 3D nuclear telomeric organization of normal and tumour cells, irrespective of their origin, appears significantly different. It is our goal to introduce the 3D telomeric signatures as a clinical tool for cancer diagnosis, cancer cell detection, treatment decisions and monitoring.
Research News - International InnovationDr Mai's research was recently profiled in the magazine "International Innovation". In the article, she describes how 3D telomere profiling can be used to diagnose, prognose and monitor cancer patients to aid clinicians in staging and treating patients. Telomere size, position, and distance can help identify whether a cell is cancerous or healthy. Telomere profiling is being used for research on Hodgkin's lymphoma, breast, thyroid and prostate cancers.
For more information about nuclear remodelling of telomeres and 3D cancer genomics, please read the following article.
International Innovation is the leading global dissemination resource for the wider scientific, technology and research communities, dedicated to disseminating the latest science, research and technological innovations on a global level. More information and a complimentary subscription offer to the publication can be found at: www.researchmedia.eu
|RIOH is a joint institute of CancerCare Manitoba and University of Manitoba|