Gene Dysregulation

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

Group Leader

What we do

Altered gene transcription is a major cause of cancer. Our group is focused on understanding altered gene transcription in cancer, with a view to identifying novel therapeutic targets and developing targeted therapies to treat children with cancer.

One of the main ways that cancer cells alter gene transcription is to chemically modify cell proteins called histones and to hack “super-enhancers” to oncogenes. These act to ‘switch off’ the transcription of genes that help suppress tumour initiation and progression, and to ‘switch on’ the transcription of genes that induce these processes. We have made significant inroads into understanding the role of histone modification and super-enhancers in the formation of tumours, and how inhibitors of histone molecules and 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 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

The critical roles of histone demethylases in neuroblastoma

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

We have found that the histone demethylase JMJD6 is over-expressed in human neuroblastoma cells and tissues, and that JMJD6-medaited histone demethylation plays important roles in tumourigenesis by modulating the expression of tumour suppressor genes and oncogenes. We have also identified a combination therapy effectively suppressing the expression of the histone demethylase JMJD6.

The critical roles of RNA methyltransferases in neuroblastoma

Contact: 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 a novel RNA methyltransferase is considerably highly expressed in human neuroblastoma tissues, and high levels of the RNA methyltransferase independently correlate with poor patient prognosis. We are currently investigating the oncogenic role of this novel RNA methyltransferase in neuroblastoma, and collaborating with drug discovery experts to develop inhibitors of the novel RNA methyltransferase.

Identification of novel non-protein-coding RNAs in neuroblastoma

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

Using non-protein-coding RNA microarray and 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 performing experiments to identify the RNA-interacting protein, and will screen a small molecule library for compounds which block the interaction.

Translational research

Enhancing the anticancer efficacy of BRD inhibitors and transcriptional kinase inhibitors

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

BRD inhibitors and transcriptional kinase inhibitors are among the most promising novel anticancer agents. We have discovered that BRD inhibitors and transcriptional kinase inhibitors exert dramatic synergistic anticancer effects in mouse models of neuroblastoma when combined with two class of anticancer agents which are both already in clinical use. As BRD inhibitors and transcriptional kinase inhibitors are currently in clinical trials in patients with various types of cancers, the discoveries are ready to be translated into clinical trials in cancer patients.

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.

Identification and characterisation of novel long non-protein-coding RNAs for the therapy of neuroblastoma

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

Through RNA-sequencing technology, we have identified two novel long non-protein-coding RNAs which have never been previously studied. We have confirmed that high levels of the novel long non-protein-coding RNAs in human neuroblastoma tissues are independent markers for poor patient survival, and therefore therapeutic targets for neuroblastoma patients. In addition, we have found that treatment with small molecule compounds which reduce the expression of the long non-protein-coding RNAs reduces cancer cell growth and survival, and that treatment of neuroblastoma-bearing mice with the combination therapy reduces tumour progression.

Team

Research Officers

Dr Andrew Tee

Dr Pei Yan Liu

Dr Matthew Wong

Research Assistants

Jingwei Chen

PhD Students

Sujanna Mondal

Jing Wu

Honours Student

Ella Karbanowicz

News & Blogs

Get in Touch

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

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