Invasion and Metastasis
Cancer invasion and metastasis occur in a complex three dimensional environment, with reciprocal feedback from the surrounding host tissue and stroma governing cancer cell behaviour. Understanding this behaviour in an intact host setting allows us to examine, in a more physiological context, the aberrant regulation of critical events that lead to dissemination and spread of the primary tumour. Intravital (in vivo) imaging is providing new insights on how cells behave in their native microenvironment thereby improving our understanding of disease progression.
In our laboratory we use novel state-of-the-art intravital imaging approaches and new fluorescent mouse models to uncouple the metastatic process into key stages in order to pinpoint critical events that drive tumour invasion and metastasis. Our approach permits real-time imaging ranging from whole body tumour progression to single-cell invasion events, and helps us to understand how tumour cell (a) dissociation (b) invasion or (c) progression are controlled and how this is linked to the development of invasive or metastatic cancer.
Video above: RhoA, Live and in Color. The small GTPase RhoA is a major signaling hub in most cells, but its actions can be difficult to track. Timpson and colleagues developed a biosensor that reveals RhoA activation in living tissues and used it to examine signaling in real time. This movie shows three prime examples. Read the full story here.
We also explore properties of the three-dimensional tumour microenvironment that contribute to poor drug targeting in order to pinpoint critical barriers that impair efficient tumour targeting. Combination therapy aimed at counteracting these barriers are then employed to enhance drug penetrance and efficiency in vivo and improve overall drug delivery outcome.
A key to our laboratory’s approach is to use established in vitro and in vivo 2D and 3D technology to examine cancer progression at a sub-cellular and molecular level in situ. Key techniques and current applications include:
- Fluorescence Lifetime Imaging (FLIM) & Fluorescence Resonance Energy transfer (FRET) analysis allow for accurate, time-dependent, monitoring of signalling events during drug treatment in a live tumour setting.
- We use Fluorescence Recovery After Photobleaching (FRAP) & Photoactivation in live tumours to examine and predict cell-cell junction turnover during early stages of cancer dissemination and invasion.
3D organotypic matrices serve as a malleable platform for the assessment of vital tumour/stromal interaction in a 3D context, providing a powerful tool to complement in vivo investigations.
Lab Awards and Honours
Claire Vennin - Best Translation Poster at Cell Signaling and Translational Implications (CSTI) 2017
Sean Warren - Palmer Innovation Prize 2017
Max Nobis - Best poster at Lorne Cancer Conference 2017
David Herrmann - awarded a Cold Spring Harbor Laboratory Travel Award (2017)
Clare Vennin - received the F1000 Associate Faculty Member Travel Grant for the Cell Biology Faculty (2016)
Claire Vennin - Stuart Furler Travel Award recipient (14th December 2016)
Claire Vennin - Best Cancer-related Poster Prize at 8th Garvan Signalling Meeting (1st November 2016, sponsored by Sydney Catalyst)
Sean Warren - Best Post Doc Presentation Prize at 7th International Nanomedicine Conference (29th June 2016)
Claire Vennin - Sydney Catalyst Research Scholarship and Top Up Awards (2016)
David Hermann - Young Garvan Award Finalist 2016: “Edgy Ideas”
Claire Vennin - 2015 Dennis Loather Student Poster Award at the Matrix Biology Society of Australia and New Zealand (30th October 2015)
Claire Vennin - Award for Best Presentation at the 23rd St Vincent's Campus Research Symposium (9th September 2015)
James Conway - Best poster at The Australian Society for Medical Research NSW Scientific Meeting 2015 (1st June 2015)
Claire Vennin - Best oral presentation award at the Sydney Catalyst Post-graduate and Early Career Symposium (29th April 2015)
Amr Allam - currently working towards a phD at the Peter MacCallum Research Institute in Melbourne with Prof. Sarah Russell (Centre for Microphotonics, Swinburne University).
Nadine Reischmann - currently working towards a phD at the University of Freiburg in Germany with Dr. Tilman Brummer (Institute for Molecular Medicine and Cell Research).
Lena Wullkopf - currently working towards a phD at the University of Copenhagen in Denmark with Dr. Janine Erler (Biotech Research and Innovation Centre).
Open source tools developed by the Timpson lab are available to download at http://github.com/timpsonlab.
3D Organotypic Matrix Database/Resource
Our 3D Organotypic Matrix Database/Resource contains over >7,100 organotypic invasion samples and embedded tissues.