Professor Marie Ranson
PhD, University of Sydney
BSc (Hons), University of NSW
Phone: + 61 2 4221 3291
Prof Ranson has an ongoing research interest in the cell and molecular biology of cancer migration, invasion and metastasis with a particular focus on the urokinase plasminogen activation system (PAS) and the putative protective role of its inhibitor SerpinB2 (PAI-2) in cancer. She also leads the pre-clinical development of targeted anti-cancer drugs, as well as improved delivery of chemotherapeutic drugs. Prof Ranson also contributes to research regarding streptococcal pathogenesis.
- Cancer Drug Discovery Group
- Centre For Medical and Molecular Bioscience
- CONCERT Translational Cancer Research Centre
- Illawarra Health and Medical Research Institute
- Proteostasis and Disease Research Centre
Lee JA, Yerbury JJ, Farrawell N, Shearer RF, Constantinescu P, Hatters DM, Schroder WA , Suhrbier A, Wilson MR, Saunders DN, Ranson M. (2015) SerpinB2 (PAI-2) Modulates Proteostasis via Binding Misfolded Proteins and Promotion of Cytoprotective Inclusion Formation. PLoS ONE 10(6): e0130136.doi:10.1371/journal.pone.0130136.
Vine KL, Lobov S, Chandran VI, Harris NLE and Ranson M. (2015) Improved Pharmacokinetic and Biodistribution Properties of the Selective Urokinase Inhibitor PAI-2 (SerpinB2) by Site-Specific PEGylation: Implications for Drug Delivery. Pharmaceutical Research, 32:1045-1054
Sanderson-Smith ML, Zhang Y, Ly D, Donahue D, Hollands A, Nizet V, Ranson M, Ploplis VA, Walker MJ, Castellino FJ. (2013) A Key Role for the Urokinase Plasminogen Activator (uPA) in Invasive Group A Streptococcal Infection. PLOS Pathogens. 9(7): e1003469. doi:10.1371/journal.ppat.1003469.
Vine KL Chandran VI, Locke JM, Matesic L, Lee J, Skropeta D, Bremner JB and Ranson M. (2012) Targeting Urokinase and the Transferrin Receptor with Novel, Anti-Mitotic N-Alkylisatin Cytotoxin Conjugates Causes Selective Cancer Cell Death and Reduces Tumor Growth. Current Cancer Drug Targets. 12:64-73
Cochran BJ, Croucher DR, Lobov, S, Saunders DN and Ranson M. (2011) Dependence on endocytic receptor binding via a minimal binding motif underlies the differential prognostic profiles of serpinE1 and serpinB2 in cancer. Journal of Biological Chemistry. 286: 24467-24475.
Matthews H, Ranson M and Kelso MJ. (2011) Anti-Tumour/Metastasis Effects of the Potassium-Sparing Diuretic Amiloride: An Orally Active Anti-Cancer Drug Waiting for its Call-of-Duty? International Journal of Cancer. 129, 2051–2061.
Vine KL, Matesic L Locke JM, Ranson M and Skropeta D. Cytotoxic and Anticancer Activities of Isatin and its Derivatives: A Comprehensive Review from 2000-2008. (2009) Anticancer Agents in Medicinal Chemistry.9:397-414
Croucher DR, Saunders DN, Lobov S and Ranson M. (2008) Revisiting the biological roles of PAI2 (SERPINB2) in cancer. Nature Reviews Cancer. 8:535-545.
Stutchbury TK, Al-ejeh F, Stillfried GE, Croucher DR, Andrews JA, Irving D, Links M and Ranson M. (2007) Preclinical evaluation of PAI-2-DTTA-213Bi (alpha-PAI-2) in an orthotopic murine xenogenic model of human breast carcinoma. Molecular Cancer Therapeutics. 6: 203-212.
Bruce Ashford, MBBS, FRACS
Title: Understanding the molecular and genetic mechanisms of metastasis in Cutaneous Squamous Cell Carcinoma (cSSC)
Using fresh tumour from metastatic skin cancer (cSCC) to analyse and characterise mutation patterns. Defining the mutational landscape to enable earlier identification and management of high risk tumours.
Daniel Brungs, MBBS, MMed FRACP
Title: Development of Patient-Derived Gastric Cancer Cell Models fo Genetic, Phenotypic and Drug Response Analysis
We are exploring the genotypic and phenotypic heterogeneity of gastroesophageal cancer using patient derived tissues with the goal of improving the personalisation of systemic treatment.
Title: Dual inhibition of Anticancer Targets uPA and NHE1
This project is aimed at the development of novel dual targeting anticancer drugs based on the clinically used potassium-sparing diuretic Amiloride. Amiloride shows moderately potent anticancer side activities in vivo. This work involves the derivatization of amiloride to increase it’s potency against two separate anticancer targets: the broad spectrum serine protease urokinase plasminogen activator (uPA, a key regulator of cancer cell invasiveness) and NHE1 (a transmembrane H+ antiporter primarily responsible for carcinogenesis and the reversed transmembrane pH gradient characteristic of cancer cells). Using a SAR guided approach we are generating and characterising compounds showing sub uM potency against both targets.
Title: Deciphering the role of SerpinB2 in cancer growth and metastasis
Understanding the role of a naturally occurring inhibitor of the plasminogen activation system (PAS), SerpinB2, in breast and pancreatic cancer growth and metastasis. Nathanial employs both mouse models and 3D organotypic culture systems, which closely recapitulates the tumour microenvironment as occurs in vivo. In addition to providing novel mechanistic insight into breast and pancreatic cancer biology and the utility of SerpinB2 for targeting the PAS, the models developed in Nathanial’s project will provide valuable platforms for future cancer therapeutics.
Title: Understanding the Biology of Metastatic Cutaneous Squamous Cell Carcinoma
To develop cell-line models of patient-derived metastatic skin cancer (cSCC), using techniques that recapitulate in vivo tumour biology, to understand the biology of this disease. Characterisation of the genotype-phenotype and therapeutic response of these cultures allows for the dissection of individual gene mutation/expression profile to drug sensitivity. Such data may guide therapies to prevent and treat metastatic cSCC.
Suggested Topics for Future Students
The urokinase plasminogen activation system in cancer invasion and metastasis. Includes the development and delivery of drugs and imaging agents in preclinical studies.
Identification of biomarkers to predict cancer responsiveness to single and combinatorial drug treatment using established and new drug approaches.
- 1990 PhD, University of Sydney
- 1985 BSc (Hons) (Biochemistry), University of NSW
ACADEMIC AND RESEARCH APPOINTMENTS
- 2015 - Professor, School of Biological Sciences, University of Wollongong
- 2014 - Illawarra Lead and CI CONCERT Translational Cancer Research Centre
- 2013 – Visiting Research Fellow, Institute of Genetics and Biophysics, National Research Council, Naples Italy
- 2009 - 2012 Scientific Director, Cancer Continuum, Illawarra Health and Medical Research Institute
- 2009 – Visiting Research Fellow, Finsen Laboratory, University of Copenhagen, Denmark
- 2006- Associate Professor, School of Biological Sciences, University of Wollongong
- 2005-2008 - Cancer Institute NSW Fellow (based at University of Wollongong)
- 2004 - Gessellschaft fur Biotechnologische Forschung (GBF) Fellow, Braunschweig, Germany
- 1998-2005 - Lecturer/Senior Lecturer, Department of Biological Sciences, University of Wollongong
- 1993-1997 - Research Fellow, Department Biological Sciences, University of Wollongong
- 1990-1992 - Fogarty Visiting Post-Doctoral Fellow, National Institutes of Health, Bethesda USA
- 2009 – Visiting Research Fellowship, University of Copenhagen
- 2007 - Winner of the University of Wollongong Vice-Chancellor’s Award for Excellence in Research Supervision (also nominated in 2011 and 2015)
- 2005 - Cancer Institute NSW Career Development and Support Fellowship (3 years)
- 2004 - Gessellschaft fur Biotechnologische Forschung (GBF) Fellowship
- 1990-1992 - Fogarty Visiting Post-Doctoral Fellowship, NIH
- 1989 - Biomedical Postgraduate Scholarship, NHMRC
- 1983/1984 - 2x Australian National Heart Foundation Vacation Scholarships
- 2014 - Member of the national Gene Technology Technical Advisory Committee
- 2013 - Member of Editorial board of Current Drug Targets journal (ISSN: 1873-5592)
- The American Society for Biochemistry and Molecular Biology
- International Society of Fibrinolysis and Proteolysis
- Metastasis Research Society