• 89 Commercial Road, Burnet Building, Level 4

    3004 Melbourne

    Australia

20132023

Research activity per year

Personal profile

Biography

She has been working as a mid-career laboratory researcher on cancer cell biology and biochemistry, and particularly on the role and regulation of EZH2 in different cancers and the immune system, for 11 years in three different laboratories. She thus has a strong record in EZH2 research in prostate cancer, melanoma and hematopoietic cells (PNAS 115:3452, IF:12.8; Oncogene 11:2631, IF: 8.8; Epigenetics 9:634, IF: 4.9). In the current lab, she identified underlying molecular mechanisms of melanoma cell heterogeneity as being linked to EZH2 expression, revealing this oncoprotein as a key negative regulator of melanocytic cell differentiation and positive regulator of malignant cell biology.  She also found that EZH2 is dominantly regulated post-translationally by protein degradation (Oncogene 11:2631, IF: 8.8) and discovered EZH2’s interactions with Kinesin1 proteins and IMPDH2, a known regulator of GTP. This raises the exciting possibility of previously unappreciated, non-canonical mechanisms of EZH2 function linked to GTP metabolism. Currently, she is working to elucidate the EZH2/IMPDH2 interaction interface using cross-linking mass spectroscopy method (CASS Foundation Grant, AUD64,000).

As further evidence of her abilities, she has also made key insights into the regulation of other important oncogenic pathways, including FGF-ERK pathway negative feedback mechanisms in retinal glial cells (IOVS 54:3526, IF: 4.9), estrogen receptor signalling in breast cancer (Journal of Molecular Cell Biology 10:273, IF:8.2), p53/Δ133p53 regulation in adaptive stress responses (Cell Death and Differentiation 27:618, IF: 15.8) and the Hippo/YAP pathway regulation in prostate cancer and melanoma (Nature Communications 6:8126, IF: 17.7, Oncogene 39:5627, IF: 8.8).

Research interests

During her PhD study she focused on receptor tyrosine kinase signaling pathway regulators in retina development and diabetic retinopathy. Her PhD work enhances our understanding of the mechanisms of Müller gliosis as a response to diseases and injury, Müller cell glucose metabolism, and the development of diabetic retinopathy in the context of FGF and insulin signaling pathway negative regulations.  During her first postdoc for almost 2 years she was working on the role of Mst1/YAP pathway in castration-resistant prostate cancer development. She identified the underlying epigenetic mechanism of Mst1 silencing during prostate cancer progression and showed the crosstalk between Hippo signaling and MYC, EZH2 in prostate cancer. In her other project, she identified the link between Hippo/YAP and AR pathways. In her second postdoc, she studied the underlying mechanism of p53 contribution on determining the tissue sensitivity to DNA damage in terms of epigenetic regulation of radiosensitive organs, such as spleen, thymus, GI tract and bone marrow cells. For this purpose, epigenetic changes are examined in isolated splenocytes, thymocytes and bone marrow cells from Mdmx mutant mice and she discovered that p53 regulates the EZH2 protein stability and in turn determines the tissue sensitivity upon radiation/chemotherapy.

Her work on the current project is based on Mark Shackleton's work on cancer heterogeneity, which led to the discovery of EZH2 regulation of the tumourigenic state of melanoma cells and subsequent biochemical studies that revealed novel EZH2 regulation, interactions and signalling mechanisms in melanoma and other EZH2-mediated cancers that may be targeted in the near future.

 

Expertise related to UN Sustainable Development Goals

In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This person’s work contributes towards the following SDG(s):

  • SDG 3 - Good Health and Well-being
  • SDG 7 - Affordable and Clean Energy

Research area keywords

  • Cancer Biology
  • Epigenetics
  • Radiation
  • p53 signaling
  • Hippo/YAP signaling
  • FGFR signaling
  • EZH2
  • Purine metabolism
  • Melanoma
  • Uveal Melanoma

Collaborations and top research areas from the last five years

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