Associate Professor Mathias Francois

Principal Research Fellow

Institute for Molecular Bioscience
m.francois@imb.uq.edu.au
+61 7 334 62494

Overview

Dr Mat Francois a molecular geneticist specialised in transcription factor biology in embryonic development and inflammation.

Mat's PhD (awarded in 2004) focused on the role of nuclear receptors PPARs in the control of the inflammatory reaction during osteoarthritis. In 2005, he moved to IMB's Koopman Group to study the role of SOX transcription factor in the control of lymphatic vessel development.

Mat launched his independent research career based on the discovery of the role of the transcription factor SOX18 as a molecular switch to induce the embryonic development of the lymphatic vessels. Following up on that finding, he's been awarded with the ASMR Queensland Premier’s award in 2009 and a UQ Foundation Research Excellence Award in 2011.

In September 2011, Mat set up his lab to focus on the initial step of endothelial cell specification and the molecular hierarchy that governs this differentiation program during embryogenesis. Recently he received a CDA (Career Development Award) to elucidate the role of SOX protein in the modulation of the lymphatic and blood vascular growth that control tumour metastasis.

Mat's strategic approach to research is now based on the combination of developmental biology and the use of pathophysiological models (e.g. cancer metastasis and lymphoedema) in combination with a drug discovery pipeline to identify novel therapeutic approaches to block cancer metastasis and manipulate transcription factor activity.

Research Interests

  • Transcriptional regulation of blood and lymphatic vessels
    Lymphatic vessels are a vital component of the vascular system and are essential for immune surveillance and maintaining fluid balance. In the adult, aberrant formation of lymphatic vessels is associated with a wide range of diseases that include chronic inflammatory disorders, such as rheumatoid arthritis, cancer metastasis and lymphoedema. Under these pathological conditions, the developmental programs that drive lymphangiogenesis become dysregulated. Therefore, understanding the molecular basis that governs normal lymphatic vessel development in the embryo is a prerequisite to further identify novel target genes and develop potential new therapeutic avenues to prevent aberrant development in adults. Our research identifies and characterises key genetic pathways influencing lymphatic vascular development in the mouse embryo. We are using pre-clinical mouse models of cancer or lymphoedema to validate the central role of developmental programs that are reactivated in these diseases. This work will help us to develop a new class of compounds that will enable the pharmacological management of the lymphatic network, with the view to explore vascular development and establish the basis for drug development. The experimental strategies we have pioneered to perform this translational research program rely on a range of tests and involve close collaborations with other IMB scientists and international research groups with expertise in zebrafish and mouse genetics, medicinal chemistry biophysics and genomics.

Research Impacts

Lymphatic vessels are a vital component of the vascular system and are essential for immune surveillance and maintaining fluid balance. In the adult, aberrant formation of lymphatic vessels is associated with a wide range of diseases that include chronic inflammatory disorders, cancer metastasis and lymphoedema. The vasculature is also centrally important in cardiovascular diseases and cancer progression.

We aim to better understand how the vasculature forms during development and to translate our findings into a deeper understanding of disease. We study several aspects of vascular development and biology.

Qualifications

  • Doctor of Philosophy, PARIS VI

Publications

  • Patel, Jatin, Seppanen, Elke J., Rodero, Mathieu, Wong, Ho Yi, Donovan, Prudence, Neufeld, Zoltan, Fisk, Nicholas, Francois, Mathias and Khosrotehrani, Kiarash (2017) Functional definition of progenitors versus mature endothelial cells reveals key SoxF-dependent differentiation process. Circulation, 135 8: 786-805. doi:10.1161/CIRCULATIONAHA.116.024754

  • Fontaine, Frank, Overman, Jeroen, Moustaqil, Mehdi, Mamidyala, Sreeman, Salim, Angela, Narasimhan, Kamesh, Prokoph, Nina, Robertson, Avril A. B., Lua, Linda, Alexandrov, Kirill, Koopman, Peter, Capon, Robert J., Sierecki, Emma, Gambin, Yann, Jauch, Ralf, Cooper, Matthew A., Zuegg, Johannes and Francois, Mathias (2017) Small-molecule inhibitors of the SOX18 transcription factor. Chemistry Chemical Biology, . doi:10.1016/j.chembiol.2017.01.003

  • Overman, Jeroen, Fontaine, Frank, Moustaqil, Mehdi, Mittal, Deepak, Sierecki, Emma, Sacilotto, Natalia, Zuegg, Johannes, Robertson, Avril A. B., Holmes, Kelly, Salim, Angela A., Mamidyala, Sreeman, Butler, Mark S., Robinson, Ashley S., Lesieur, Emmanuelle, Johnston, Wayne, Alexandrov, Kirill, Black, Brian L., Hogan, Benjamin M., De Val, Sarah, Capon, Robert J., Carroll, Jason S., Bailey, Timothy L., Koopman, Peter, Jauch, Ralf, Smyth, Mark J., Cooper, Matthew A., Gambin, Yann and Francois, Mathias (2017) Pharmacological targeting of the transcription factor SOX18 delays breast cancer in mice. eLife, 6 . doi:10.7554/eLife.21221

View all Publications

Grants

View all Grants

Supervision

  • Doctor Philosophy

  • Doctor Philosophy

  • Doctor Philosophy

View all Supervision

Publications

Journal Article

Conference Publication

  • Aspelund, Aleksanteri, Tammela, Tuomas, Antila, Salli, Nurmi, Harri, Leppanen, Veli-Matti, Zarkada, Georgia, Stanczuk, Lukas, Francois, Mathias, Makinen, Taija, Saharinen, Pipsa, Immonen, Ilkka and Alitalo, Kari (2015). Therapeutic Insights to Lymphangiogenic Growth Factors. In: European Society for Microcirculation (ESM) / European Vascular Biology Organisation (EVBO): Joint Meeting, Abstracts. Joint Meeting of the European-Society-for-Microcirculation (ESM) and European-Vascular-Biology-Organisation (EVBO), Pisa, Italy, (19-19). 03-06 June 2015. doi:10.1159/000433498

  • Nguyen, C., Skoczylas, R., Pichol-Thievend, C., Frampton, E., Rannou, F. and Francois, M. (2014). Forelimb Development in the Mouse: An Original Model of Organo-Dependent Lymphangiogenesis. In: 15th Annual European Congress of Rheumatology (EULAR), Paris, France, (835-835). 11-14 June 2014. doi:10.1136/annrheumdis-2014-eular.3954

  • Moon, Hyeongsun, Sharpe, Laura, Choi, Eunju, Bielefeldt-Ohmann, Helle, Nassar, Zeyad, Parat, Marie-Odile, Francois, Mathias, Lee, C. Soon, Brown, Andrew, Russell, Pamela, Inder, Kerry and Hill, Michelle (2014). Hypercholesterolemia promotes prostate cancer PC-3 metastases in orthotopic xenograft mice. In: Proceedings: AACR Annual Meeting 2014. 105th Annual Meeting of the American Association for Cancer Research (AACR), San Diego, CA United States, (). 05-09 April 2014. doi:10.1158/1538-7445.AM2014-4950

  • Cermenati, Solei, Moleri, Silvia, Neyt, Christine, Bresciani, Erica, Carra, Silvia, Grassini, Daniela R., Omini, Alice, Cotelli, Franco, Francois, Mathias, Hogan, Benjamin M. and Beltrame, Monica (2013). Sox18 and VegfC genetically interact in the early phases of lymphatic development in zebrafish. In: NAVBO Workshops in Vascular Biology, Pacific Grove, CA, United States, (250-250). 14-18 October 2012. doi:10.1007/s10456-012-9326-5

  • Hodgson, S. S., Francois, M. and Khosrotehrani, K. (2012). A mouse model for in vivo quantitative monitoring of Wnt/b-catenin signaling in skin reveals hair cycle dynamics in sox18 mutant mice. In: Abstracts 22nd Annual Meeting of the European Tissue Repair Society. 22nd Annual Meeting of the European Tissue Repair Society, Athens, Greece, (A59-A59). October 4–5 2012. doi:10.1111/j.1524-475X.2012.00835.x

  • Benallaoua, Mourad, Richette, Pascal, Francois, Mathias, Tsagris, Lydia, Revel, Michel, Corvol, Maité, Poiraudeau, Serge, Savouret, Jean-François and Rannou, François (2006). Modulation of proteoglycan production by cyclic tensile stretch in intervertebral disc cells through a post-translational mechanism. In: Selected papers of the 4th International Symposium on Mechanobiology of Cartilage and Chondrocyte. 4th International Symposium on Mechanobiology of Cartilage and Chondrocyte, Budapest, Hungary, (303-310). 20–22 May 2006.

Grants (Administered at UQ)

PhD and MPhil Supervision

Current Supervision

  • Doctor Philosophy — Principal Advisor

  • Doctor Philosophy — Principal Advisor

  • Doctor Philosophy — Principal Advisor

  • Doctor Philosophy — Principal Advisor

  • Doctor Philosophy — Associate Advisor

    Other advisors:

Completed Supervision