Department of Breast and Molecular Oncology

Overview

My research is focused on mechanisms of cancer development and progression. Specifically, I’m interested in the ubiquitin/proteasome system, serine protease inhibitors and combining the use of high-throughput gain/loss of function genetic screens with novel fluorescent assays and high-content imaging.

A key challenge in biomedical research is to define the function of proteins encoded by various disease-related genes. The development of integrated functional genomics technology and its application to novel experimental models represent a rapid and powerful new means to understand gene function, define biological pathways, and identify novel therapeutic strategies. This approach will become increasingly important as the various cancer genome sequencing projects now underway identify molecular targets for cancer diagnosis/therapy. A major bottleneck in these studies is the functional validation of putative novel tumour gene mutations, which is critical for understanding the huge wealth of information being generated.

Education/Experience

• PhD – Biological Sciences, University of Wollongong, Australia, 2000
• BSc (Hons) – Biological Sciences, University of Wollongong, Australia, 1995
• Snr Research Officer (postdoc) – Cancer Research Program, Garvan institute of Medical Research

Research Projects

• High-throughput protein interaction screens using Bimolecular Fluorescence Complementation (BiFC) and the human ORFeome.
• Regulation of iPS cell reprogramming
• Functional characterisation of E3 Ubiquitin ligases (e.g. UBR5/EDD1).
• Structure-function relationships in serpins.

Selected Publications

1. Saunders D. Backlogged system in Australia shuts out new investigators. Nature 458 (7236) , 281 (2009)
2. Croucher D, Saunders D, Lobov S, Ranson M. Revisiting the biological roles of PAI2 (SERPINB2) in cancer. Nature reviews. Cancer 8 (7) , 535-45 (2008)
3. Lobov S, Croucher D, Saunders D, Ranson M. Plasminogen activator inhibitor type 2 inhibits cell surface associated tissue plasminogen activator in vitro. Potential receptor interactions Thromb Haemost
4. Saunders D. Ubr5 Nature Molecule Pages (2008)
5. O’Brien P, Davies M, Scurry J, Smith A, Barton C, Henderson M, Saunders D, Gloss B, Patterson K, Clancy J, Heinzelmann-Schwarz V, Scolyer R, Zeng Y, Williams E, Scurr L, DeFazio A, Quinn D, Watts C, Hacker N, Henshall S, Sutherland R. The E3 ubiquitin ligase EDD is an adverse prognostic factor for serous epithelial ovarian cancer and modulates cisplatin resistance in vitro Br J Cancer98 (6) , 1085 – 1093 (2008)
6. Poon S, Wong J, Saunders D, Ma Q, McKinney S, Fee J, Aparicio S. Intensity calibration and automated cell cycle gating for high-throughput image-based siRNA screens of mammalian cells. Cytometry. Part A : the journal of the International Society for Analytical Cytology 73 (10) , 904-17 (2008)
7. Croucher D, Saunders D, Stillfried G, Ranson M. A structural basis for differential cell signalling by PAI-1 and PAI-2 in breast cancer cells Biochem. J. 408 (2)
8. McGowan E, Russell A, Boonyaratanakornkit V, Saunders D, Lehrbach G, Sergio C, Musgrove E, Edwards D, Sutherland R. Progestins reinitiate cell cycle progression in antiestrogen-arrested breast cancer cells through the B-isoform of progesterone receptor. Cancer research 67 (18) , 8942-51 (2007)
9. Munoz M, Saunders D, Henderson M, Clancy J, Russell A, Lehrbach G, Musgrove E, Watts C, Sutherland R. The E3 ubiquitin ligase EDD regulates S-phase and G(2)/M DNA damage checkpoints. Cell cycle (Georgetown, Tex.) 6 (24) , 3070-7 (2007) (Epub 07 Sep 2007) PubMed ID:(18073532)
10. Stillfried G, Saunders D, Ranson M. Plasminogen binding and activation at the breast cancer cell surface: the integral role of urokinase activity. Breast cancer research : BCR 9 (1) , R14 (2007) PubMed ID:(17257442)
11. Croucher D, Saunders D, Ranson M. The urokinase/PAI-2 complex: a new high affinity ligand for the endocytosis receptor low density lipoprotein receptor-related protein. The Journal of biological chemistry 281 (15) , 10206-13 (2006) (Epub 03 Feb 2006) PubMed ID:(16459332)
12. Henderson M, Munoz M, Saunders D, Clancy J, Russell A, Williams B, Pappin D, Khanna K, Jackson S, Sutherland R, Watts C. EDD mediates DNA damage-induced activation of CHK2. The Journal of biological chemistry 281 (52) , 39990-40000 (2006) (Epub 30 Oct 2006) PubMed ID:(17074762)
13. Withington S, Scott A, Saunders D, Lopes Floro K, Preis J, Michalicek J, Maclean K, Sparrow D, Barbera J, Dunwoodie S. Loss of Cited2 affects trophoblast formation and vascularization of the mouse placenta. Developmental biology 294 (1) , 67-82 (2006) (Epub 31 Mar 2006) PubMed ID:(16579983)
14. Saunders D, Hird S, Withington S, Dunwoodie S, Henderson M, Biben C, Sutherland R, Ormandy C, Watts C. Edd, the murine hyperplastic disc gene, is essential for yolk sac vascularization and chorioallantoic fusion. Molecular and cellular biology 24 (16) , 7225-34 (2004) PubMed ID:(15282321)
15. Jankova L, Harrop S, Saunders D, Andrews J, Bertram K, Gould A, Baker M, Curmi P. Crystal structure of the complex of plasminogen activator inhibitor 2 with a peptide mimicking the reactive center loop. The Journal of biological chemistry 276 (46) , 43374-82 (2001) (Epub 23 Aug 2001) PubMed ID:(11546761)
16. Saunders D, Jankova L, Harrop S, Curmi P, Gould A, Ranson M, Baker M. Interaction between the P14 residue and strand 2 of beta-sheet B is critical for reactive center loop insertion in plasminogen activator inhibitor-2. The Journal of biological chemistry 276 (46) , 43383-9 (2001) PubMed ID:(11555638)
17. Saunders D, Buttigieg K, Gould A, McPhun V, Baker M. Immunological detection of conformational neoepitopes associated with the serpin activity of plasminogen activator inhibitor type-2. The Journal of biological chemistry 273 (18) , 10965-71 (1998) PubMed ID:(9556575)

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