The Steinberg Centre for Simulation and Interactive Learning at McGill University.

Simulation allows for learner-centered health professions training by providing a safe environment to practice and make mistakes without jeopardizing patient care. It was with this goal in mind that the McGill Medical Simulation Center was officially opened on September 14, 2006, as a partnership between McGill University, the Faculty of Medicine and its affiliated hospitals. Its mandate is to provide state-of-the-art facilities to support simulation-based medical and allied health education initiatives. Since its inception, the center, recently renamed the Steinberg Center for Simulation and Interactive Learning (SCSIL), has undergone a major expansion and logged more than 130,000 learner visits. Educational activities are offered at all levels of medical and allied health care training, and include standardized patient encounters, partial task trainers, multidisciplinary courses, and high-fidelity trainers, among many others. In addition to its educational mandate, the center also supports an active research program, programs to enhance collaboration with disciplines outside of health care to spur innovation, and community outreach initiatives.

Characterization of nuclear factors modulating the apolipoprotein D promoter during growth arrest: implication of PARP-1, APEX-1 and ERK1/2 catalytic activities.

Human Apolipoprotein D (apoD) is upregulated under several stress conditions and pathological situations such as neurodegenerative diseases and cancers. We previously showed that apoD mRNA expression is induced in growth-arrested cells and demonstrated the specific binding of nuclear proteins to the region -514 to -475 of the promoter. Such region contains a pair of Serum Responsive Elements (SRE), an Ets-Binding Site (EBS) and a Glucocorticoid Responsive Element (GRE). In this study, we show that Parp-1, HnRNP-U, CBF-A, BUB-3, Kif4, APEX-1 and Ifi204 bind these regulatory elements of the apoD promoter. Specific binding of HnRNP-U and Parp-1 was confirmed by Electrophoretic Mobility Shift Assay (EMSA). In a biotin pull-down assay, Kif4 and BUB-3 bind preferentially the SRE1 and the EBS-GRE sites, respectively, while APEX-1 seems recruited indirectly to these elements. We found that the mRNA expression of some of these binding factors is upregulated in growth-arrested cells and that these proteins also transactivate the apoD promoter. In agreement with these results, mutants of APEX-1 and of Parp-1 defective for their DNA-binding and catalytic activities could not transactivate the promoter. The knockdown of Parp-1 and HnRNP-U and the use of specific inhibitors of MEK1/2 and of Parp-1 also inhibited the induction of apoD gene expression. Moreover, ERK1/2 was found activated in a biphasic manner post serum-starvation and the inhibition of Parp-1 causes a sustained activation of ERK2 but not ERK1 for up to 2h. Altogether, these findings demonstrate the importance of Parp-1, APEX-1 and ERK1/2 catalytic activities in the growth arrest-induced apoD gene expression.

Gene profiling of the erythro- and megakaryoblastic leukaemias induced by the Graffi murine retrovirus.

BACKGROUND: Acute erythro- and megakaryoblastic leukaemias are associated with very poor prognoses and the mechanism of blastic transformation is insufficiently elucidated. The murine Graffi leukaemia retrovirus induces erythro- and megakaryoblastic leukaemias when inoculated into NFS mice and represents a good model to study these leukaemias. METHODS: To expand our understanding of genes specific to these leukaemias, we compared gene expression profiles, measured by microarray and RT-PCR, of all leukaemia types induced by this virus. RESULTS: The transcriptome level changes, present between the different leukaemias, led to the identification of specific cancerous signatures. We reported numerous genes that may be potential oncogenes, may have a function related to erythropoiesis or megakaryopoiesis or have a poorly elucidated physiological role. The expression pattern of these genes has been further tested by RT-PCR in different samples, in a Friend erythroleukaemic model and in human leukaemic cell lines.We also screened the megakaryoblastic leukaemias for viral integrations and identified genes targeted by these integrations and potentially implicated in the onset of the disease. CONCLUSIONS: Taken as a whole, the data obtained from this global gene profiling experiment have provided a detailed characterization of Graffi virus induced erythro- and megakaryoblastic leukaemias with many genes reported specific to the transcriptome of these leukaemias for the first time.

Oncogenic potential of the miR-106-363 cluster and its implication in human T-cell leukemia.

We previously reported the identification of the Kis2 common retrovirus integration site, located on mouse chromosome X, in radiation leukemia virus-induced T-cell leukemias. Tumors with a provirus at the Kis2 locus overexpressed a novel noncoding RNA (ncRNA) with a complex splicing pattern and no polyA tail. Database upgrade revealed the presence of a microRNA (miRNA) cluster, miR-106-363, just downstream of the Kis2 ncRNAs. We found that Kis2 ncRNAs are the pri-miRNA of miR-106-363, and we present evidence that Kis2 ncRNA overexpression in mouse tumors results in miR-106a, miR-19b-2, miR-92-2, and miR-20b accumulation. We show the oncogenic potential of those miRNAs in anchorage independence assay and confirm pri-miR-106-363 overexpression in 46% of human T-cell leukemias tested. This overexpression contributes in rising miR-92 and miR-19 levels, as this is the case for miR-17-92 cluster overexpression. Furthermore, we identified myosin regulatory light chain-interacting protein, retinoblastoma-binding protein 1-like, and possibly homeodomain-interacting protein kinase 3 as target genes of this miRNA cluster, which establishes a link between these genes and T-cell leukemia for the first time.