Prof Geoff Lindeman, Division Head | WEHI Researcher Profile

Q: Dissection of the mammary stem cell and progenitor compartments

This project involves lineage tracing and transplantation studies, state of the art 3D imaging and the analysis of targeted models for defects in the stem/progenitor cell compartment. The importance of developmental pathways in establishing the hierarchy at different stages will also be investigated, by the specific ablation of cell types using cre-loxP and diphtheria toxin technologies.Related article: Long-lived breast stem cells could retain cancer legacy [https://www.wehi.edu.au/news/long-lived-breast-stem-cells-could-retain-cancer-legacy]Image: https://www.dropbox.com/s/br3urzqk0ae242h/breast-cancer-lab-mammary-gland.jpg?dl=0

Q: Generation of genetically engineered models to identify cells of origin of breast cancer

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.

Q: Use of preclinical patient-derived xenograft (PDX) models of breast cancer

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 BCL2 family inhibitors), exploring the metastasis and cancer stem cells. This work has the potential of identifying new biomarkers and therapeutic targets for breast cancer. Related article: Anti-cancer compound shows promise for breast cancer [https://www.wehi.edu.au/news/new-anti-cancer-compound-shows-promise-breast-cancer]

About

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.

Education

Joint appointments

Grants and funding

Publications

Selected publications from Prof Geoff Lindeman

Lok SW, Whittle JR, Vaillant F, Teh 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 MM, Bujak AZ, Dawson S-J, 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):10.1158/2159-8290.cd-18-1151

Nolan E, Vaillant F, Branstetter D, Pal B, Giner G, Whitehead L, Lok SW, Mann GB, Rohrbach K, Huang L-Y, 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 Medicine. 2016;22(8):10.1038/nm.4118

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):10.1016/j.ccr.2013.06.002

Asselin-Labat M-L, 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):10.1038/nature09027

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, 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):10.1038/nm.2000

Shackleton M, Vaillant F, Simpson KJ, Stingl J, Smyth GK, Asselin-Labat M-L, Wu L, Lindeman GJ, Visvader JE. Generation of a functional mammary gland from a single stem cell. Nature. 2006;439(7072):10.1038/nature04372

Pascual R, Cheng J, De Smet AH, Capaldo BD, Tsai M, Kordafshari S, Vaillant F, Song X, Giner G, Milevskiy MJG, Jackling FC, Pal B, Dite T, Yousef J, Dagley LF, Smyth GK, Fu N, Lindeman GJ, Chen Y, Visvader JE. Fibroblast hierarchy dynamics during mammary gland morphogenesis and tumorigenesis. The EMBO Journal. 2025;:10.1038/s44318-025-00422-3

Chin HS, Cheng J, Hsu SH, Lum GG, Zaldivia MT, Nelameham S, Guo F, Mallavarapu K, Jackling FC, Yang J, Tan JSL, Sampath P, Barker N, Smyth GK, Lindeman GJ, Strasser A, Visvader JE, Chen Y, Chen T, Fu NY. MCL‑1 safeguards activated hair follicle stem cells to enable adult hair regeneration. Nature Communications. 2025;16(1):10.1038/s41467-025-58150-5

Luo M-X, Tan T, Trussart M, Poch A, Nguyen TMH, Speed TP, Hicks DG, Bandala-Sanchez E, Peng H, Chappaz S, Slade C, Utzschneider DT, Koldej RM, Ritchie D, Strasser A, Thijssen R, Ritchie ME, Tam CS, Lindeman GJ, Huang DCS, Lew TE, Anderson MA, Roberts AW, Teh CE, Gray DHD. Venetoclax dose escalation rapidly activates a BAFF/BCL-2 survival axis in chronic lymphocytic leukemia. Blood. 2024;144(26):10.1182/blood.2024024341

Dawson CA, Milevskiy MJG, Capaldo BD, Yip RKH, Song X, Vaillant F, Prokopuk L, Jackling FC, Smyth GK, Chen Y, Lindeman GJ, Visvader JE. Hormone-responsive progenitors have a unique identity and exhibit high motility during mammary morphogenesis. Cell Reports. 2024;43(12):10.1016/j.celrep.2024.115073

Muttiah C, Martin F, Christie M, Dawson S-J, Desai J, Lal L, Moodie K, Murugasu A, Phan P, Rosenthal M, Travers A, Visvader J, Whittle JR, Lindeman G. 361P PALVEN: A phase Ib study of palbociclib, letrozole and venetoclax in ER and BCL2-positive metastatic breast cancer. Annals of Oncology. 2024;35:10.1016/j.annonc.2024.08.309

Mukohara T, Park YH, Sommerhalder D, Yonemori K, Hamilton E, Kim S-B, Kim JH, Iwata H, Yamashita T, Layman RM, Mita M, Clay T, Chae YS, Oakman C, Yan F, Kim GM, Im S-A, Lindeman GJ, Rugo HS, Liyanage M, Saul M, Le Corre C, Skoura A, Liu L, Li M, LoRusso PM. Inhibition of lysine acetyltransferase KAT6 in ER+HER2− metastatic breast cancer: a phase 1 trial. Nature Medicine. 2024;30(8):10.1038/s41591-024-03060-0

Mukohara T, Park YH, Sommerhalder D, Yonemori K, Hamilton E, Kim S-B, Kim JH, Iwata H, Yamashita T, Layman RM, Mita M, Clay T, Chae YS, Oakman C, Yan F, Kim GM, Im S-A, Lindeman GJ, Rugo HS, Liyanage M, Saul M, Le Corre C, Skoura A, Liu L, Li M, LoRusso PM. Author Correction: Inhibition of lysine acetyltransferase KAT6 in ER+HER2− metastatic breast cancer: a phase 1 trial. Nature Medicine. 2024;30(8):10.1038/s41591-024-03129-w

McDonald JA, Liao Y, Knight JA, John EM, Kurian AW, Daly M, Buys SS, Huang Y, Frost CJ, Andrulis IL, Colonna SV, Friedlander ML, Hopper JL, Chung WK, Genkinger JM, MacInnis RJ, Terry MB, Amor D, Andrews L, Antill Y, Balleine R, Beesley J, Bennett I, Bogwitz M, Bodek S, Botes L, Brennan M, Brown M, Buckley M, Burke J, Butow P, Caldon L, Campbell I, Cao M, Chakrabarti A, Chauhan D, Chauhan M, Chenevix-Trench G, Christian A, Cohen P, Colley A, Crook A, Cui J, Courtney E, Cummings M, Dawson S-J, deFazio A, Delatycki M, Dickson R, Dixon J, Edwards S, Farshid G, Fellows A, Fenton G, Field M, Flanagan J, Fong P, Forrest L, Fox S, French J, Friedlander M, Gaff C, Gattas M, George P, Greening S, Harris M, Hart S, Harraka P, Hayward N, Hopper J, Hoskins C, Hunt C, James P, Jenkins M, Kidd A, Kirk J, Koehler J, Kollias J, Lakhani S, Lawrence M, Lee J, Li S, Lindeman G, Lippey J, Lipton L, Lobb L, Loi S, Mann G, Marsh D, McLachlan SA, Meiser B, Milne R, Nightingale S, O’Connell S, O’Sullivan S, Gallego Ortega D, Pachter N, Pang J-M, Pathak G, Patterson B, Pearn A, Phillips K, Pieper E, Ramus S, Rickard E, Ragunathan A, Robinson B, Saleh M, Skandarajah A, Salisbury E, Saunders C, Saunus J, Savas P, Scott R, Scott C, Sexton A, Shaw J, Shelling A, Srinivasa S, Simpson P, Southey M, Spurdle A, Taylor J, Taylor R, Thorne H, Trainer A, Tucker K, Visvader J, Walker L, Williams R, Winship I, Young MA, Zaheed M. Pregnancy-Related Factors and Breast Cancer Risk for Women Across a Range of Familial Risk. JAMA Network Open. 2024;7(8):10.1001/jamanetworkopen.2024.27441

Mukohara T, Park YH, Sommerhalder D, Yonemori K, Kim S-B, Kim JH, Iwata H, Yamashita T, Layman RM, Kim GM, Im S-A, Lindeman GJ, Rugo HS, Liyanage M, Homji Mishra N, Maity A, Bogg O, Liu L, Li M, LoRusso P. A phase 1 dose expansion study of a first-in-class KAT6 inhibitor (PF-07248144) in patients with advanced or metastatic ER+ HER2− breast cancer.Journal of Clinical Oncology. 2024;42(16_suppl):10.1200/jco.2024.42.16_suppl.3006

Campbell I, Devereux L, Hogg K, Lal L, Sinclair M, Stafford L, Zethoven M, Skandarajah A, James P, Lindeman G, Mann B, De Silva D. Abstract PO2-08-11: The MAGIC study: Universal whole genome tumour and germline sequencing of newly diagnosed breast cancer identifies a high proportion of ER+ BRCA-like tumours. Cancer Research. 2024;84(9_Supplement):10.1158/1538-7445.sabcs23-po2-08-11