Gene Dysregulation

Our group studies altered gene expression in cancer so we can develop new ways to treat cancer in children.

Group Leader

What we do

Altered gene expression is a major cause of cancer. Our group is focused on understanding altered gene transcription and RNA modification in cancer initiation and progression, with a view to identifying drug-like inhibitors and developing targeted therapies to treat children with cancer.

One of the main ways that cancer cells alter gene transcription is to “rearrange” critical oncogenic genes to the neighbourhood of transcriptional ‘super-enhancers’. This acts to massively augment the transcription of oncogenes that induce tumour initiation and progression. We have made significant inroads into understanding the role of super-enhancers in the formation of tumours, and how inhibitors of super-enhancers can act as anticancer agents.

We are also using a genomics approach to investigate the genes and molecular pathways critically involved in driving tumour growth in neuroblastoma, focusing on genetic subtypes of high-risk neuroblastoma. We recently found evidence that long non-coding RNAs and RNA methyltransferases may be critical drivers of neuroblastoma, and became one of the first groups in the world to develop inhibitors of these molecules.

Research projects

Basic research

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Identification of RNA methyltransferases as tumourigenic drivers and the discovery of small molecule compound inhibitors for cancer therapy

Contacts: A/Prof Tao Liu, tliu@ccia.org.au

RNA methylation is emerging as a critical regulator of tumour initiation and progression. Through examining human neuroblastoma tissue RNA sequencing data, we have found that two novel RNA methyltransferases are considerably highly expressed in human neuroblastoma tissues, and high levels of the RNA methyltransferases independently correlate with poor patient prognosis. We are currently investigating the oncogenic roles of these novel RNA methyltransferases in neuroblastoma, and developing inhibitors of the novel RNA methyltransferases to treat neuroblastoma and potentially other cancers.

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Identification of novel non-protein-coding RNAs as tumourigenic drivers and discovery of small molecule compound inhibitors for cancer therapy

Contact: A/Prof Tao Liu, tliu@ccia.org.au

Using next-generation RNA sequencing technologies, we have identified novel non-protein-coding RNAs, which may play critical roles in neuroblastoma initiation and progression. Suppression of one of the novel non-protein-coding RNAs leads to neuroblastoma regression or complete eradication. We are currently screening a small molecule library for compounds which block the tumourigenic function of long non-protein-coding RNAs to treat cancer.

Translational research

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Experimental therapy of the under-studied but deadly TERT oncogene-rearranged neuroblastoma

Contact: A/Prof Tao Liu, tliu@ccia.org.au

Discovered in 2015, TERT oncogene-rearranged neuroblastoma accounts for a quarter of high-risk neuroblastoma. The majority of patients with this subtype of neuroblastoma die of the disease. Currently, no targeted therapy is available for clinical trials. We are currently examining the anticancer efficacy of inhibitors of super-enhancer “readers” and “writers”, and striving to discover efficacious therapies for this under-studied but very deadly subtype of neuroblastoma for clinical translation in patients.

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Developing rapid diagnosis of TERT oncogene-rearranged neuroblastoma

Contact: A/Prof Tao Liu, tliu@ccia.org.au

TERT oncogene-rearranged neuroblastoma is currently diagnosed by long-read whole genome sequencing which is expensive and time-consuming. We are developing a quick and easy diagnostic tool to diagnose TERT gene-rearranged neuroblastoma so that patients can be treated early.

Team

Research Officers

Dr Sujanna Mondal

Dr Jing Wu

PhD Students

Dian Anggraini

Kian Chung Chok

Sahar Mafi

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!