Prof Jane Visvader, Division Head | WEHI Researcher Profile

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 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. 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

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.

Education

Joint appointments

Publications

Selected publications from Prof Jane Visvader

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

Ang CH, Arandjelovic P, Cheng J, Yang J, Guo F, Yu Y, Nelameham S, Whitehead L, Li J, Silver DL, Barker N, Visvader JE, Chow PKH, Smyth GK, Chen Y, Virshup DM, Fu NY. Self-maintenance of zonal hepatocytes during adult homeostasis and their complex plasticity upon distinct liver injuries. Cell Reports. 2025;44(1):10.1016/j.celrep.2024.115093

Joyce R, Visvader JE. Cells-of-Origin of Breast Cancer and Intertumoral Heterogeneity. Advances in Experimental Medicine and Biology. 2025;1464:10.1007/978-3-031-70875-6_9

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

Visvader JE. Midkine links aging with breast cancer—A new predictor of cancer risk. Cancer Cell. 2024;42(11):10.1016/j.ccell.2024.09.003

Altman JE, Olex AL, Zboril EK, Walker CJ, Boyd DC, Myrick RK, Hairr NS, Koblinski JE, Puchalapalli M, Hu B, Dozmorov MG, Chen XS, Chen Y, Perou CM, Lehmann BD, Visvader JE, Harrell JC. Single‐cell transcriptional atlas of human breast cancers and model systems. Clinical and Translational Medicine. 2024;14(10):10.1002/ctm2.70044

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

Nightingale R, Reehorst CM, Vukelic N, Papadopoulos N, Liao Y, Guleria S, Bell C, Vaillant F, Paul S, Luk IY, Dhillon AS, Jenkins LJ, Morrow RJ, Jackling FC, Chand AL, Chisanga D, Chen Y, Williams DS, Anderson RL, Ellis S, Meikle PJ, Shi W, Visvader JE, Pal B, Mariadason JM. Ehf controls mammary alveolar lineage differentiation and is a putative suppressor of breast tumorigenesis. Developmental Cell. 2024;59(15):10.1016/j.devcel.2024.04.022

Visvader JE, Rosen JM, Aparicio S. Breast Cancer. Cold Spring Harbor Perspectives in Medicine. 2024;14(8):10.1101/cshperspect.a041729