Cancer and Stem Cell Biology 

Westudy how normal stem cells are transformed into cancer stem cells and develop effective stem cell-targeted therapies. 

Group Leader

What we do

Our Group’s main research focus is developing effective new therapies that specifically target and destroy cancer stem cells. These cells, which are often resistant to current therapies such as chemotherapy and radiation therapy, are now believed to be the engine driving the growth of cancer and the root cause of treatment resistance and relapse.

Stem cells are capable of dividing indefinitely to produce copies of themselves (self-renewal) and generate multiple cell types. When certain genetic and epigenetic abnormalities occur in stem cells, they hijack self-renewal mechanisms and multiply out of control, causing cancer. These cells can evade chemotherapy and re-initiate tumour growth, leading to relapse. To cure a child’s cancer, we need to eradicate the cancer stem cells from which the disease originates. Targeted disruption of abnormal stem cell self-renewal represents a new therapeutic strategy and is becoming a central focus in new drug development.

Our objectives are to:

  • understand the mechanisms by which normal stem cells are transformed into abnormal stem cells
  • identify critical drug targets for malignant stem cell eradication
  • develop effective stem cell-targeted therapies to treat poor-prognosis leukaemia. 

Our main funding sources include the National Health and Medical Research Council, Cancer Australia, Leukaemia Foundation, and Tour de Cure.

Research Projects

Targeting of leukaemia stem cells for the development of curative therapies

Contact: Dr Jenny Wang, jwang@ccia.org.au

Acute myeloid leukaemia (AML) is a difficult-to-treat blood cancer with a much lower survival rate than that of acute lymphoblastic leukaemia (ALL). Despite intensive chemotherapy, many children with AML relapse and ultimately die from their disease.

Clinical evidence has highlighted the important role of leukaemia stem cells in the high relapse rate of AML. Leukaemia stem cells reside in a mostly quiescent (resting) state and, as such, are resistant to commonly used anti-proliferation cytotoxic agents. These cells possess several unique features, including increased self-renewal, blocked differentiation, and escape from cell death. These features caused by driver mutations and genetic/epigenetic abnormalities distinguish leukaemia stem cells from normal stem cells. Targeted elimination of leukaemia stem cells is now believed to be essential to achieve complete remission in children treated for AML.

We have identified key self-renewal pathways (Science 2010; Blood 2014; Leukemia 2016; Cancer Cell 2020) for AML stem cell formation, and our exciting findings of pathway inhibitors provide promising new therapeutic opportunities to specifically target leukaemia stem cells. Through a better understanding of the mechanism of action of these inhibitors, we hope to develop more effective stem cell-targeted therapies. This research will generate new insights into leukaemia stem cell biology and provide pre-clinical validation of therapeutic potential.

Epigenetic regulation of leukaemia stem cells - developing new epigenetic therapies

Contact: Dr Jenny Wang, jwang@ccia.org.au

Epigenetic regulation of gene expression plays a crucial role in stem cell functions. Inappropriate maintenance of epigenetic ‘marks’ that sit on the nuclear DNA of cancer cells and control the activity of genes results in activation of oncogenic self-renewal pathways. This leads to the formation of leukaemia stem cells and subsequent development of leukaemia. Unlike genetic alterations, epigenetic marks can be reversed by treatment with chromatin-modifying drugs, making them suitable targets for epigenetic-based therapies.

Our studies have identified several new epigenetic regulators that contribute to leukaemia formation and progression. This project aims to explore epigenetic mechanisms that govern leukaemia stem cell function and to discover clinical drugs that are capable of reversing cancer-associated epigenetic marks. Through this research we hope to identify epigenetic targets crucial for leukaemia stem cell survival, with the potential to lead to novel epigenetic therapies.

Developing RNA-based therapeutics to eradicate leukaemia stem cells

Contact: Dr Jenny Wang, jwang@ccia.org.au

The recent discovery of non-coding RNAs (ncRNAs) has dramatically altered our view of gene regulation in cancer. ncRNAs can serve as regulatory molecules, playing a pivotal role in cancer progression and metastasis. Despite increasing evidence highlighting their importance in cancer, understanding of ncRNAs is still very limited.

Our studies have identified new ncRNAs and uncovered a complex RNA regulatory network. This project aims to understand the regulatory mechanism of ncRNAs in leukaemia stem cell biology. The knowledge gained from this study will provide compelling evidence for developing innovative RNA-based therapeutics targeting leukaemia stem cells.

Team

Research Officers

Nunki Hassan

Honours Students

Claudia Furdi

Niamh Craw

Sayali Gore

News & Blogs

Get in Touch

Do you have a question about our work? For any enquiries please don’t hesitate to contact us.

Your donation will fund research that will save young lives!