*Seminar Series: QIMR BERGHOFER
*Location: Auditorium, Level 3, Central Building, QIMR Berghofer
*Date: 09/08/2017
*Time: 13:00

Speaker #1 details
*Title of talk: BRN2 - the master regulator of melanoma invasion
*Speaker's name: Dr Aaron Smith
*Speaker's organisation: QUT
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Talk Abstract: Phenotypic divergence of sub-populations of tumour cells is known to underpin alternative behaviours linked to tumour progression. Heterogeneity between two transcription factors in melanoma cells, BRN2 and MITF, has been associated with phenotypic switching between invasive and proliferative behaviours respectively, thereby allowing adaptation to micro- environmental conditions such as hypoxia, nutrient deprivation and drug treatment. The mechanism by which the phenotypic switch occurs is unclear. We have recently identified the NFIB transcription factor as a novel downstream effector of BRN2 function in melanoma cells linked to migratory and invasive characteristics. NFIB appears to drive an invasive phenotype via the upregulation of the polycomb group protein EZH2. Notably, NFIB mediated up-regulation of EZH2 decreases MITF expression, further promoting a less proliferative, more invasive phenotype. Our data reveals that NFIB promotes dynamic changes in the chromatin state of melanoma cells to facilitate migration, invasion and metastasis. Also BRN2 co- ordinates survival responses to environmental cues and alters metabolic functions in BRN2-high invasive sub-population. This offers a potential targeting strategy using novel anticancer agents that de-stabilize mitochondrial function.
Speaker's bio: Dr Smith\\\'s work on the BRN2 transcription factor began in 1995 when he began exploring gene regulation in melanoma as part of an Honours project with A/Prof Richard Sturm, IMB, followed by a PhD in the same laboratory. A Postdoctoral Fellowship at the University of Cambridge, UK, in 2001 was a departure from cancer gene regulation but was an opportunity to gain expertise in Nuclear Receptor biology in metabolic disease. Returning to Australia in 2004, Dr Smith was able to continue working on nuclear receptor function in the context of melanoma and revisit the role of BRN2 in driving phenotype switching in melanoma cells. In 2010 he established an independent research group in the School of Biomedical Research at The University of Queensland, continuing work on gene regulation in melanocyte and melanoma cell function. In 2016 he moved to the QUT, Institute for Health and Biomedical Innovation, Translational Research Institute. In addition to investigating the BRN2-MITF transcriptional axis in melanoma, his other research interests include functional analysis of genes and genetic variants associated with nevus count and/or melanoma susceptibility including IRF4, PLA2G6, MTAP and MC1R, and nuclear receptor regulation of DNA repair.

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Other Details:
*Host name: QIMR Berghofer
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*Host email: events@qimrberghofer.edu.au