Dr Samantha Oakes

Group Leader - Cell Survival

Conjoint/Adjunct Role(s)

Conjoint Senior Lecturer, St Vincent's Clinical School, Faculty of Medicine, UNSW Australia

Samantha Oakes received her PhD in Medical Science from the Garvan/St Vincent’s Clinical School, University of New South Wales in 2007, with funding from a NHMRC Dora Lush scholarship. The focus of her PhD was on understanding the role of prolactin receptor and its downstream targets during mammary gland development and cancer and she received the Garvan Institute of Medical Research thesis prize for this work.

Samantha’s work showed for the first time that the prolactin receptor was important for the earliest phases of carcinogenesis, and re-ignited the importance of the role of prolactin for breast cancer. These data also provided a potential explanation for the observation in the US Nurses Health Study that post-menopausal women with top quartile serum prolactin conferred a 2-fold higher relative risk of developing breast cancer.

Samantha’s work also contributed to the discovery that the Elf5 (a prolactin regulated gene) is the principal mediator of the alveolar cell fate for the mammary epithelium during pregnancy, and that it segregated with steroid-receptor positive mammary epithelial cells. The later result has important clinical applications for the treatment of basal-like breast cancer, and more recently has led to the discovery that Elf5 drives the claudin-low sub-type of breast cancer and is essential for the proliferation of estrogen insensitive breast cancers.

In 2008, Samantha received NHMRC Peter Doherty and National Breast Cancer Foundation fellowships and embarked on a Postdoctoral position at the Walter and Eliza Hall Institute of Medical Research, Melbourne. The focus of her work during this time was to investigate the efficacy of BH3 mimetics for the treatment of breast cancer. Here, Samantha demonstrated that the BH3-mimetic ABT-737, which has high affinity for the pro-survival protein BCL-2, sensitised BCL-2 expressing triple negative breast cancers to conventional chemotherapy. ABT-737 is the lead compound for the new and orally available Navitoclax and ABT-199, which are currently in Phase I/II clinical trials for hematopoietic malignancies and will likely be extended to patients diagnosed with breast cancer.

In 2012, Samantha returned to Garvan to continue her work into understanding the cues that regulate cell survival in the mammary gland and in breast cancer. In 2013 Samantha received a National Breast Cancer Foundation Early Career Fellowship and has been appointed as Group leader. Samantha now leads a small team focussed on Cell Survival in the larger Cancer Biology laboratory headed by Professor Christopher Ormandy. Samantha remains committed to community participation and engagement through television and print media as well as public seminars and tours of the Garvan Institute.

Research Interests

Cell survival
Apoptosis
Cancer biology
Cancer genetics
Breast cancer
Cancer therapy
Cancer research
Mammary development
Stem cells

Awards and Honours

2015 - National Breast Cancer Foundation Spirit of Giving Award ‘Excellence in Science Communication Award’
2013-2016 - NBCF Early Career Fellowship
2008-2010 - NHMRC Peter Doherty Australian-based Biomedical Postdoctoral Research Fellowship. 2008-2010 NBCF Postdoctoral Research Fellowship
2003-2006 - NHMRC Dora Lush Pre-doctoral Research Scholarship
2012 - The University of Sydney Medal for Excellence in Medical Research for the Best Overall Presentation NSW Scientific Meeting, Sydney, Australia
2012 - National Breast Cancer Foundation Patron’s Award for ‘Excellence in Science and Science Communication Award’ Awarded by the Governor General of Australia Ms Quentin Bryce and Sarah Murdoch (Patron of the National Breast Cancer Foundation)
2008 - Outstanding Oral Presentation 2008 Prolactin and Growth Hormone Gordon Research Conference, Ventura, California, USA
2007 - Garvan Institute Thesis Prize, Sydney, Australia
2007 - The Eli Lilly Award for the Best Student Oral Presentation, NSW ASMR Scientific Meeting, Sydney, Australia
2006 - The Cancer Institute Award for Excellence in Student Oral Presentation. 16th St Vincent’s and Mater Health Sydney Research Symposium, Sydney, Australia

Education

2007 - PhD (Medical Research), University of New South Wales (Garvan Institute of Medical Research) - Australia
1999 - BSc (Hons1) Anatomy, University of New South Wales - Australia

Selected Publications

Piggin CL, Roden DL, Gallego-Ortega D, Lee HJ, Oakes SR, Ormandy SR ELF5 Isoform Expression is Tissue-Specific and Significantly Altered in Cancer. 2016 Breast Cancer Research 2016 Jan 7;18(1):4

Gallego-Ortega D, Ledger A, Roden D, Magenau A, Law AMK, Kikhtyak ZO, Cho C, Allerdice SL, Lee HJ, Valdes-Mora F, Young AIJ, Lee BW , Kaplan W, Salomon R, Piggin C, Hermann D, Conway J, Rabinovich B, Millar E, Oakes SR, Chtanova T, Swarbrick A, Naylor MJ, O’Toole S, Timpson P, Gee JMW, Ellis I, Clark SJ  and Ormandy CJ. The ETS transcription factor ELF5 drives lung metastasis in luminal breast cancer via recruitment of Gr-1+CD11b+ myeloid derived suppressor cells. 2015 PLOS Biology Dec 30;13(12)

Hilton HN, Doan TB, Graham JD, Oakes SR, Silvestri A, Santucci N, Kantimm S, Huschtscha LI, Ormandy CJ, Funder JW, Simpson ER, Kuczek ES, Leedman PJ, Tilley WD, Fuller PJ, Muscat GEO, Clarke CL. Acquired convergence of hormone signaling in breast cancer: ER and PR transition from functionally distinct in normal breast to predictors of metastatic disease. 2014. Oncotarget 5(18), 8651. 

Oakes SR, Gallego-Ortega D and Ormandy CJ. The mammary cellular hierarchy 2014. Cellular and Molecular Life Sciences 71 (22), 4301-4324.

Gallego-Ortega D, Oakes SR, Lee HJ, Piggin CL and Ormandy CJ. Elf5, normal mammary development, and the heterogeneous phenotypes of breast cancer. Breast Cancer Management 2013 2(6):489-498 

O’Toole SA, Beith JM, Millar EKA, West R, McLean A, Cazet A, Swarbrick A and Oakes SR. Therapeutic targets in triple negative breast cancer. Journal of Clinical Pathology 2013; 66(6):530-42

Kalyuga M, Gallego-Ortega D, Lee HJ, Roden DL, Cowley MJ, Caldon CE, Stone A, Allerdice SL, Valdes-Mora F, Launchbury R, Statham AL, Armstrong N, Alles MC, Young A, Egger A, Au W, Piggin CL, Evans CJ, Ledger A, Brummer T, Oakes SR, Kaplan W, Gee JM, Nicholson RI, Sutherland RL, Swarbrick A, Naylor MJ, Clark SJ, Carroll JS, Ormandy CJ. ELF5 suppresses estrogen sensitivity and underpins the acquisition of antiestrogen resistance in luminal breast cancer. Plos Biology 2012; 10(12):e1001461

Oakes SR, Vaillant F, Lim E, Lee L, Breslin K, Feleppa F, Deb S, Ritchie ME, Takano E, Ward T, Fox SB, Generali D, Smyth GK, Strasser A, Huang DC, Visvader JE, Lindeman GJ. Sensitization of BCL-2 expressing breast tumors to chemotherapy by the BH3 mimetic ABT-737. Proc Natl Acad Sci U S A. 2012; 109(8): 2766-71.

Bouras T, Pal B, Vaillant F, Harburg G, Asselin-Labat ML, Oakes SR, Lindeman GJ, Visvader JE. Notch Signaling Regulates Mammary Stem Cell Function and Luminal Cell-Fate Commitment. Cell Stem Cell, 2008; 9 (3): 429-441.

Oakes SR, Naylor MJ, Asselin-Labat ML, Blazek KD, Gardiner-Garden M, Hilton HN, Kazlauskas M, Pritchard MA, Chodosh LA, Pfeffer PL, Lindeman GJ, Visvader JE, Ormandy CJ. The Ets transcription factor Elf5 specifies mammary alveolar cell fate. Genes Dev. 2008; 22(5):581-6.

Oakes SR, Rogers RL, Naylor MJ, Ormandy CJ. Prolactin regulation of mammary gland development. J Mammary Gland Biol Neoplasia. 2008; 13(1):13-28.

Hilton HN, Stanford PM, Harris J, Oakes SR, Kaplan W, Daly RJ, Ormandy CJ. KIBRA interacts with discoidin domain receptor 1 to modulate collagen-induced signalling. Biochim Biophys Acta. 2008; 1783(3):383-93.

Oakes SR, Robertson FG, Kench JG, Gardiner-Garden M, Wand MP, Green JE and Ormandy CJ. Loss of mammary epithelial prolactin receptor delays tumor formation by reducing cell proliferation in low-grade preinvasive lesions. Oncogene 2007; 26(4): 543-53.

Oakes SR, Hilton HN, Ormandy CJ. Key stages in mammary gland development - The alveolar switch: coordinating the proliferative cues and cell fate decisions that drive the formation of lobuloalveoli from ductal epithelium. Breast Cancer Res. 2006; 8(2):207.

Harris J, Stanford PM, Sutherland K, Oakes SR, Naylor MJ, Robertson FG, Blazek KD, Kazlauskas M, Hilton HN, Wittlin S, Alexander WS, Lindeman GJ, Visvader JE, Ormandy CJ. (2006) Socs2 and Elf5 mediate prolactin-induced mammary gland development. Mol Endocrinol. 2006; 20(5):1177-87.

Naylor MJ*, Oakes SR*, Gardiner-Garden M, Harris J, Ho TWC, Li FC, Wynick D, Walker AM and Ormandy CJ.(2005). Transcriptional changes underlying the secretory activation stage of mammary gland development. Mol Endocrinol. 2005; 19(7):1868-83. (* Joint first authors)

Harris J, Stanford PM, Oakes SR and Ormandy CJ. Prolactin and the prolactin receptor - new targets of an old hormone. Ann. Med. 2004; 36(6):414-25

Robertson FG, J, Harris J, Naylor MJ, Oakes SR, Kindblom J,  Dillner K, Wennbo H, Tornell J, Kelly PA, Green J, Ormandy CJ. Prostate development and carcinogenesis in prolactin receptor knockout mice. Endocrinology 2003; 144(7): 3196-205.

Sainsbury-Salis A, Couzens M, Oakes SR, Ormandy CJ, Herzog H. Y4 receptor knockout rescues fertility in ob/ob mice. Genes Dev 2002; 16:1077-1088.

Dr Samantha Oakes