My research focuses on the role of stem cell biology in breast development and cancer. Together with Professor Geoff Lindeman, the Breast Cancer Laboratory has a long-standing interest in the stem cell differentiation hierarchy, identifying molecular regulators of normal development and deciphering mechanisms that lead to breast cancer.
Current efforts are directed towards further understanding the normal epithelial hierarchy and the cell subtypes that are most susceptible to becoming transformed in vivo, the so- called ‘cells of origin’. We are searching for markers that enable further purification and in situ tracking of stem cells to enhance our understanding of the heterogeneity that lies within this pool, using a combination of transplantation and cell lineage tracing studies.
We are also identifying transcriptional and epigenetic regulators that act along the hierarchy using gene-targeted models and CRISPR/CAS9 technology. Promoter-specific strains built in the laboratory enable us to interrogate both mammary gland development and potential cells of origin of cancer.
Using the latest single cell and spatial platforms, we are interrogating tumour heterogeneity at the gene expression and epigenetic levels as well as mapping the location of diverse cells in the tumour microenvironment. In conjunction, we are using multiplexed immunostaining platforms with >40 antibodies to identify and localise stromal and immune cells more precisely within tumours.
Australia, The University of Adelaide, BSc (Hons) PhD
University of Melbourne
2022 Ziskin Prize, Stand Up to Cancer (joint award)
2022 Fellow of the American Association for Cancer Research (AACR) Academy
2020 Fellow of the Royal Society (FRS)
2019 Brinker Award for Scientific Excellence, Komen Foundation (joint award)
2017 The Victoria Prize in the Life Sciences (joint award)
2016 Lemberg Medal, The Australian Society for Biochemistry and Molecular Biology
Cancer Council Victoria, Medical & Scientific Committee and Board Member
Pal B, Chen Y, Vaillant F, Capaldo BD, Joyce R, Song X, Bryant VL, Penington JS, Di Stephano L, Tubau Ribera N, Wilcox S, Mann, GB, kConFab, Papenfuss AT, Lindeman GJ, Smyth GK*, Visvader JE*. A single-cell RNA expression atlas of normal, preneoplastic and tumorigenic states in the human breast. EMBO J. 2021 40(11): e107333 PMID: 33950524 *equal senior authors
Dawson CA, Pal B, Vaillant F, Gandolfo LC, Liu Z, Bleriot C, Ginhoux F, Smyth GK, Lindeman GJ, Mueller SN, Rios AC, Visvader JE. Tissue-resident ductal macrophages survey the mammary epithelium and facilitate tissue remodelling. Nature Cell Biol. 2020 22(5), 546-558. PMID: 32341550
Rios AC, Capaldo BD, Vaillant F, Pal B, van Ineveld R, Dawson CA, Chen Y, Nolan E, Fu NY; 3DTCLSM Group, Jackling FC, Devi S, Clouston D, Whitehead L, Smyth GK, Mueller SN, Lindeman GJ, Visvader JE. Intraclonal Plasticity in Mammary Tumors Revealed through Large-Scale Single-Cell Resolution 3D Imaging. Cancer Cell. 2019 35(4), 618-632 PMID: 31185217
Fu NY, Rios AC, Pal B, Law C, Jamieson P, Liu R, Vaillant F, Jackling F, Liu KH, Smyth GK, Lindeman GJ, Ritchie ME, and Visvader JE. Identification of quiescent and spatially-restricted mammary stem cells that are hormone responsive. Nature Cell Biol. 2017 19(3):164-176 PMID: 28192422
Nolan E, Vaillant F, Branstetter D, Pal B, Giner G, Whitehead L, Lok SW, Mann GB, Rohrbach K, Huang LY, Soriano R, Smyth GK, Dougall WC, Visvader JE* and Lindeman GJ*. (2016) RANK ligand as a potential target for breast cancer prevention in BRCA1-mutation carriers. Nat Med. 2016 Jun 20. doi: 10.1038/nm.4118. PMID: 27322743 *equal senior author
Rios AC, Fu NY, Lindeman GJ, Visvader JE. In situ identification of bipotent stem cells in the mammary gland. Nature. 2014 Feb 20;506(7488):322-7. PMID: 24463516.
Asselin-Labat ML, Vaillant F, Sheridan JM, Pal B, Wu D, Simpson ER, Yasuda H, Smyth GK, Martin TJ, Lindeman GJ, Visvader JE. Control of mammary stem cell function by steroid hormone signalling. Nature. 2010;465(7299):798-802. PMID: 20383121
Lim E, Vaillant F, Wu D, Forrest NC, Pal B, Hart AH, Asselin-Labat M-L, Gyorki DE, Ward T, Partanen A, Feleppa F, Huschtscha LI, Thorne HJ, kConFab, Fox SB, Yan M, French JD, Brown MA, Smyth GK, Visvader JE*, Lindeman GJ*. Aberrant luminal progenitors as the candidate target population for basal tumor development in BRCA1 mutation carriers. Nature Med. 2009;15(8), 907-913. PMID: 19648928 *equal senior author
Asselin-Labat ML, Sutherland KD, Barker H, Thomas R, Shackleton M, Forrest NC, Hartley L, Robb L, Grosveld FG, van der Wees J, Lindeman GJ, Visvader JE. Gata-3 is an essential regulator of mammary-gland morphogenesis and luminal-cell differentiation. Nature Cell Biology. 2007;9(2):201-9. PMID: 17187062
Shackleton M, Vaillant F, Simpson KJ, Stingl J, Smyth GK, Asselin-Labat ML, Wu L, Lindeman GJ, Visvader JE. Generation of a functional mammary gland from a single stem cell. Nature. 2006;439(7072):84-8. PMID: 16397499
This involves the generation of oncogene and tumour suppressor-driven models, as well as the tracking of the earliest events in neoplasia by lineage tracing in combination with 3D imaging. Multiple models of oncogenesis have been generated for the analysis of the preneoplastic and neoplastic phases, at both the cellular and molecular levels.
We have established a large bank of PDX models that represent the various subtypes of breast cancer and recapitulate the primary tumour in the patient. These represent powerful pre-clinical models for testing novel therapies (eg BCL-2 family inhibitors), exploring the metastasis and cancer stem cells. This work has the potential of identifying new biomarkers and therapeutic targets for breast cancer.
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