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

Potts MA, Mizutani S, Deng Y, Vaidyanathan S, Ting KE, Giner G, Sridhar S, Shenoy G, Liao Y, Diepstraten ST, Kueh AJ, Pal M, Healey G, Tai L, Wang Z, König C, Kaloni D, Whelan L, Milevskiy MJG, Coughlan HD, Pomilio G, Wei AH, Visvader JE, Papenfuss AT, Wilcox S, Jeyasekharan AD, Shi W, Lelliott EJ, Kelly GL, Brown KK, Strasser A, Herold MJ. Genome-wide in vivo CRISPR screens identify GATOR1 complex as a tumor suppressor in Myc-driven lymphoma. Nature Communications. 2025;16(1):10.1038/s41467-025-62615-y

Chin HS, Cheng J, Hsu SH, Lum GG, Zaldiva MT, Guo F, Mallavarapu K, Jackling FC, Smyth GK, Lindeman GJ, Strasser A, Visvader JE, Chen Y, Chen T, Fu NY. Abstract P51: MCL-1 safeguards activated hair follicle stem cells to enable adult hair regeneration. Cancer Research. 2025;85(15_Supplement):10.1158/1538-7445.fcs2024-p51

Pham MT, Milevskiy MJG, Visvader JE, Chen Y. Incorporating exon–exon junction reads enhances differential splicing detection. BMC Bioinformatics. 2025;26(1):10.1186/s12859-025-06210-4

Lindeman G, Muttiah C, Martin FC, Christie M, Dawson S-J, Desai J, Lal L, Moodie K, Murugasu A, Phan P, Rosenthal MR, Travers A, Visvader JE, Whittle JR, Yeo B. Abstract P2-07-18: Results from PALVEN: A Phase 1b Study of Palbociclib, Letrozole and Venetoclax in ER and BCL2-Positive Metastatic Breast Cancer. Clinical Cancer Research. 2025;31(12_Supplement):10.1158/1557-3265.sabcs24-p2-07-18

Altman J, 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. Abstract P5-06-19: Single-cell transcriptional features of human breast tumors and model systems. Clinical Cancer Research. 2025;31(12_Supplement):10.1158/1557-3265.sabcs24-p5-06-19

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;44(11):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