I am a clinician-scientist and Joint Head of the ACRF Cancer Biology and Stem Cells Division and Breast Cancer Laboratory. I am also a medical oncologist at the Peter MacCallum Cancer Centre and Royal Melbourne Hospital and hold an honorary appointment as Professorial Fellow in the Department of Medicine, Royal Melbourne Hospital, University of Melbourne.
After medical oncology training in Sydney (RPA and Westmead Hospitals), I obtained my PhD at WEHI (Harris and Cory Laboratories), and then pursued postdoctoral training at the Dana-Farber Cancer Institute/Harvard Medical School Livingston Laboratory).
On return to Australia, Professor Jane Visvader and I established a Breast Cancer Laboratory. Our group is studying molecular regulators of normal mammary gland development and cancer, with a particular interest in understanding how mammary stem cells and their progeny contribute to the mammary epithelial cell hierarchy and breast cancer. This work led to the discovery of RANK-positive progenitors as a target for breast cancer prevention in BRCA1 mutation carriers. Our laboratory is also using patient derived xenograft (PDX) and tumor organoid models to test promising anti-cancer agents.
Preclinical studies using BH3 mimetics have led to early phase studies of the BCL2 inhibitor venetoclax in breast cancer.
Australia, University of Sydney, BSc(Med)
Australia, University of Sydney, MB BS(Hons)
Australia, Royal Australasian College of Physicians, FRACP
Australia, The University of Melbourne, PhD
Peter MacCallum Cancer Centre
The Royal Melbourne Hospital
The University of Melbourne
2007, Eric Susman Prize, Royal Australasian College of Physicians
2008, GlaxoSmithKline Research Excellence Award (joint with Jane Visvader)
2010, National Breast Cancer Foundation Award for Innovation (joint with Jane Visvader)
2013, The Robert Sutherland Award for Excellence in Translational Research, Breast Cancer Trials Australia
2014, Medical Oncology Group of Australia – Novartis Oncology Cancer Achievement Award
2015, Election as Fellow Australian Academy of Health and Medical Sciences (FAHMS)
2016, Election as Fellow Australian Academy of Science (FAA)
2016, Ramaciotti Medal for Excellence in Biomedical Research (joint with Jane Visvader)
2017, Victoria Prize for Science and Innovation (Life Sciences, joint with Jane Visvader)
2019, Brinker Award for Scientific Distinction, Susan G Komen Foundation, USA (joint with Jane Visvader)
2019, Kellaway Excellence Award for Translational Research
2022, Laura Zisken Stand Up 2 Cancer, USA (joint with Jane Visvader)
2020-2024, Leadership Fellowship (L3), NHMRC
Scientific Advisory Boards: National Breast Cancer Foundation, National Stem Cell Foundation of Australia and Cancer Science Institute (Singapore), Victorian Cancer Biobank, Pfizer, AbbVie.
Board Member: National Stem Cell Foundation of Australia, Executive member kConFab (Kathleen Cuningham Foundation Consortium for research into Familial Breast cancer). Former Board Member Breast Cancer Trials.
Editorial Boards: Breast Cancer Research, J Mammary Gland Biol Neoplasia, Frontiers Oncology
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. *Equal senior author.
Asselin-Labat ML, Shackleton M, Stingl J, Vaillant F, Forrest NC, Eaves CJ, Visvader JE, Lindeman GJ. Steroid hormone receptor status of mouse mammary stem cells.
J Natl Cancer Inst. 2006 98(14), 1011-4. PMID: 16849684
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. Nat Cell Biol. 2007 9(2), 201-9. PMID: 17187062
Lim E, Vaillant F, Wu D, Forrest NC, Pal B, Hart AH, Asselin-Labat ML, Gyorki DE, Ward T, Partanen A, Feleppa F, Huschtscha LI, Thorne HJ, 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 Medicine. 2009 15(8):907-13. PMID: 19648928.
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.
Vaillant F, Merino D, Lee L, Breslin K, Pal B, Ritchie ME, Smyth GK, Christie M, Phillipson LJ, Burns CJ, Mann GB, Visvader JE, Lindeman GJ. Targeting BCL-2 with the BH3 Mimetic ABT-199 in Estrogen Receptor-Positive Breast Cancer. Cancer Cell. 2013 24(1):120-9. PMID: 23845444
Rios AC, Fu NY, Lindeman GJ, Visvader JE. In situ identification of bipotent stem cells in the mammary gland. Nature. 2014 506(7488):322-7. PMID: 24463516.
Fu NY, Rios AC, Pal B, Soetanto R, Lun AT, Liu K, Beck T, Best SA, Vaillant F, Bouillet P, Strasser A, Preiss T, Smyth GK, Lindeman GJ*, Visvader JE*. EGF-mediated induction of Mcl-1 at the switch to lactation is essential for alveolar cell survival. Nat Cell Biol. 2015 17(4), 365-75. PMID: 25730472 *Equal senior author.
Nolan E, Vaillant F, Branstetter DB, Pal B, Giner G, Whitehead L, Lok SW, Mann GB, kConFab, Rohrbach K, Huang LY, Soriano R, Smyth GK, Dougall WC, Visvader JE*, Lindeman GJ*. RANK ligand as a potential target for breast cancer prevention in BRCA1 mutation carriers. Nature Med. 2016 22(8):933–939. PMID: 27322743 *Equal senior author.
Rios AC, Fu NY, Jamieson PR, Pal B, Whitehead L, Nicholas KR, Lindeman GJ, Visvader JE. Essential role for a novel population of binucleated mammary epithelial cells in lactation.
Nat Commun. 2016 7, 11400. PMID: 27102712
Nolan E, Savas P, Policheni AN, Darcy PK, Vaillant F, Mintoff C, Mariam Mansour M, Pang J-MB, Fox SB, kConFab, Perou CM, Visvader JE, Gray DHD*, Loi S*, Lindeman GJ*. Combined immune checkpoint blockade as a therapeutic strategy for BRCA1-mutated breast cancer. Sci Transl Med. 2017 9(393), eaal4922. PMID: 28592566 *Equal senior author.
Merino D, Whittle JR, Vaillant F, Serrano A, Gong J-N, Giner G, Maragno A-L, Chanrion M, Schneider E, Pal B, Li X, Dewson G, Gräsel J, Liu K, Lalaoui N, Segal D, Herold MJ, Huang D, Smyth GK, Geneste O, Lessene G, Visvader JE, Lindeman GJ. Synergistic action of the MCL-1 inhibitor S63845 with current therapies in preclinical models of triple negative and HER2-amplified breast cancer. Sci Transl Med. 2017 9(401), eaam7049. PMID: 28768804
Lok SW, Whittle JR, Vaillant F, The CE, Lo LL, Policheni AN, Bergin ART, Desai J, Ftouni S, Gandolfo LC, Liew D, Liu HK, Mann GB, Moodie K, Murugasu A, Pal B, Roberts AW, Rosenthal MA, Shackleton K, Silva MJ, Siow ZR, Smyth GK, Taylor L, Travers A, Yeo B, Yeung M, Zivanovic Bujak A, Dawson SJ, Gray DHD, Visvader JE, Lindeman GJ. A phase 1b dose-escalation and expansion study of the BCL-2 inhibitor venetoclax combined with tamoxifen in ER and BCL-2–positive metastatic breast cancer. Cancer Discovery. 2019 9(3):354-369. PMID 30518523
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.e6. PMID: 30930118
Dekkers JF, Whittle JR, Vaillant F, Chen HR, Dawson C, Liu K, Geurts MH, Herold MJ, Clevers H, Lindeman GJ, Visvader JE. Modeling breast cancer using CRISPR-Cas9-mediated engineering of human breast organoids. J Natl Cancer Inst. 2020 112(5):540-544. PMID: 31589320
Whittle JR, Vaillant F, Surgenor E, Policheni AN, Giner G, Capaldo BD, Chen HR, Liu HK, Dekkers JF, Sachs N, Clevers H, Fellowes A, Green T, Xu H, Fox SB, Herold MJ, Smyth GK, Gray DHD, Visvader JE, Lindeman GJ. Dual targeting of CDK4/6 and BCL2 pathways augments tumor response in estrogen receptor-positive breast cancer. Clin Cancer Res. 2020 26(15), 4120-4134. PMID: 32245900
Pal B, Chen Y, Milevskiy MJG, Vaillant F, Prokopuk L, Dawson CA, Capaldo BD, Song X, Jackling F, Timpson P, Lindeman GJ, Smyth GK, Visvader JE. Single cell transcriptome atlas of mouse mammary epithelial cells across development. Breast Cancer Res. 2021 J23(1), 69. PMID: 34187545
Pal B, Chen Y, Vaillant F, Capaldo BD, Joyce R, Song X, Bryant VL, Penington JS, Di Stefano 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
Lindeman GJ, Fernando TM, Bowen R, Jerzak KJ, Song X, Decker T, Boyle F, McCune S, Armstrong A, Shannon C, Bertelli G, Chang CW, Desai R, Gupta K, Wilson TR, Flechais A, Bardia A. VERONICA: Randomized phase 2 study of fulvestrant and venetoclax in ER-positive metastatic breast cancer post-CDK4/6 inhibitors – efficacy, safety, biomarker results. Clin Cancer Res. 2022 28(15), 3256-3267. PMID: 35583555
Nolan E, Lindeman GJ*, Visvader JE* Deciphering Breast Cancer: from biology to the clinic. Cell 2023 Mar 13:S0092-8674(23)00099-5. doi: 10.1016/j.cell.2023.01.040. Online ahead of print. PMID: 36931265 *Equal senior author
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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