Blood Cancer and Immunotherapy Laboratory

Our research focus

Human cancers harbour defects in processes that inhibit or enhance tumour growth, so-called tumour suppressor and oncogenes. Importantly, these abnormalities render the tumour cells resistant to many therapies.

Our research is focused on understanding how cancers develop and finding new therapy approaches, including targeted drugs as well as immune therapies to treat these cancers.

We aim to identify novel genes involved in the development of normal and malignant haematopoiesis. We are using in vivo CRISPR approaches to systematically identify new candidate genes, with the ultimate goal of using these targets as novel anti-cancer therapies.

We have recently also started to understand the mechanisms of therapy resistance in cancers and how we can overcome this by reducing the fitness of the cancer cells or enhancing immune therapies using different CRISPR approaches.

Recent publications

Cell death & Differentiation

Combined absence of TRP53 target genes ZMAT3, PUMA and p21 cause a high incidence of cancer in mice

DOI: 10.1038/s41418-023-01250-w

18 December 2023

View abstract
CELL DEATH & DIFFERENTIATION

Genome-wide CRISPR screening identifies a role for ARRDC3 in TRP53-mediated responses

DOI: 10.1038/s41418-023-01249-3

14 December 2023

View abstract
Stem Cell Reports

Integration of xeno-free single-cell cloning in CRISPR-mediated DNA editing of human iPSCs improves homogeneity and methodological efficiency of cellular disease modeling

DOI: 10.1016/j.stemcr.2023.10.013

12 December 2023

View abstract

Our team

Meet our researchers

  • Prof Marco Herold - Head, Blood Cancer and Immunotherapy Laboratory & Chief Executive Officer Publications
  • Andrew Kueh - CRISPR Platform Lead
  • Lin Tai - Laboratory Manager
  • Kieran Lau - CRIPSR Microinjection Lead
  • Yexuan Deng - Postdoctoral Research Fellow
  • Goknur Giner - Postdoctoral Research Fellow
  • Christina Koenig - Postdoctoral Research Fellow
  • Eddie Lamarca - Postdoctoral Research Fellow
  • Emily Lelliott - Postdoctoral Research Fellow
  • Maggie Potts - Postdoctoral Research Fellow
  • Geraldine Healey - Senior Research Assistant
  • Jonathan Cebon - Honorary
  • Amali Cooray - PhD Student
  • Wei Jin - PhD Student
  • Gaoyuan Wang - PhD Student

Molecular Immunology Laboratory

Our research focus

Identification of tumour immune evasion mechanisms

Cancer immune evasion is a major hurdle in for the success of current immunotherapies, both in the context of adoptive cellular therapy (ACT) and immune checkpoint blockade. Despite the clinical success of diverse immunotherapies, many patients do not respond or ultimately relapse, likely due to tumours evolving to escape sufficient recognition by the immune system. Although considerable progress has been made in understanding how cancers evade immunity, measures to counteract tumour immune escape are lacking. We employ cutting-edge screening mechanisms to identify tumour immune evasion mechanisms and avenues to sensitise tumour cells to T cell-mediated killing.

Genetic/epigenetic control of effective anti-tumour T cell responses

Despite the success of adoptive cellular therapy (ACT) in the context of haematological malignancies, response rates against solid malignancies are poor, likely due to tumour-associated immunosuppression and subsequent T cell exhaustion. Indeed, it is becoming clear that the failure of T cells to elicit a successful and long-term anti-tumour immune response is controlled by transcriptional, epigenetic and post-translational modifications. However, our current understanding of the molecules involved in these processes is limited. We use cutting-edge technology including in vitro and in vivo CRISPR screens, high throughput drug screens and novel single cell sequencing protocols to identify novel underlying molecular mechanisms leading to T cell dysfunction in cancer and identify mechanisms to improve T cell function in this context. We employ a variety of pre-clinical models of CAR T cell therapy and re-directed TCR T cell therapy to validate novel immunotherapy targets for translation into the clinic.

Identification of novel immunotherapy approaches.

High-throughput screening has been a staple in drug discovery in recent decades. Target-based drug discovery relies heavily on singular readouts such as reporter gene expression or perturbation of enzymatic activity in response to small molecule treatment. However, with a recent renewed focus on phenotypic based drug discovery, there is an increased interest in more comprehensive and less biased screening methods that combine aspects of both target-based and phenotypic screening, such as RNA-seq. To complement our genetic screens, we also perform high-throughput drug screens for agents that promote favourable states of T cell differentiation for anti-tumour immunity and agents that increase the immunogenicity of cancer cells. Importantly, identification of such agents would allow us to enhance current immunotherapy approaches.

Fast facts

Adoptive cellular therapy, also known as cellular immunotherapy, is a form of treatment that uses the cells of our immune system to eliminate cancer. Some of these approaches involve directly isolating our own immune cells and simply expanding their numbers and re-introducing into a patient, whereas others involve genetically engineering our immune cells (via gene therapy) to enhance their anti-cancer functions.

CD8+ T cells (often called cytotoxic T lymphocytes, or CTLs) are critical for immune defence against pathogens including viruses and bacteria, but also for detecting and killing cells that have become cancerous. When a CD8+ T cell recognises its antigen and becomes activated, it can directly kill pathogen infected cells or cancer cells through direct contact, but also release soluble factors called cytokines which alert other cells of the immune system.

CRISPR is a powerful tool for editing genomes, meaning it allows researchers to easily alter DNA sequences and modify gene function. CRISPR technology was adapted from the natural immune defence mechanisms of bacteria and archaea, species of relatively simple single-celled microorganisms.

Recent publications

THE FEBS JOURNAL

Tumor immune evasion: insights from CRISPR screens and future directions

DOI: 10.1111/febs.17003

16 November 2023

View abstract
PNAS

Rationally designed chimeric PI3K-BET bromodomain inhibitors elicit curative responses in MYC-driven lymphoma

DOI: 10.1073/pnas.2306414120

29 August 2023

View abstract
Cell Reports

CRISPR-Cas9 screening identifies an IRF1-SOCS1-mediated negative feedback loop that limits CXCL9 expression and antitumor immunity

DOI: 10.1016/j.celrep.2023.113014

20 August 2023

View abstract

Our team

Meet our researchers

  • Maide Salehi - PhD Student
  • Akash Srivaths - PhD Student

Tissue and Tumour Immunity Laboratory

Our research focus

Tumour infiltrating regulatory T cells

Our body’s immune system can recognise and effectively eliminate tumours. To escape immune attack, tumours hijack a specialised immune cell population known as regulatory T cells (Tregs), which potently suppresses anti-tumour immune cells to promote tumour growth. Targeting Tregs, therefore, is an attractive strategy to revert immune suppression in tumours and boost the function of anti-tumour immune cells. Our laboratory aims to discover transcriptional and epigenetic mechanisms employed by Tregs to infiltrate tumours in vital organs such as the gut, lung, liver and brain. These mechanisms will be harnessed to target Tregs for the treatment of solid tumours.

Stromal-immune cell crosstalk

Tumour microenvironment is composed of actively proliferating tumour cells, stromal cells, blood vessels and a plethora of immune cells. Stromal cells are known to produce a variety of growth factors and immunomodulatory molecules that directly shapes the immune landscape of tumours. We use cutting-edge molecular tools and microscopy to understand the molecular makeup of stromal cells in diverse tissues and tumours as well as their crosstalk with immune cells, in particular Tregs.

Metabolic regulation of tumour immunity

Cellular metabolism is critical for the differentiation, growth and function of tumour cells and immune cells. Metabolic intermediates serve as catalysts for several cellular processes including gene transcription. Systemic metabolic changes also influence anti-tumour immune responses and immunotherapy outcomes. Our laboratory aims to understand how cellular metabolism and tumour derived ‘oncometabolites’ shape the transcriptional landscape of tumour infiltrating immune cells. We also investigate how changes in systemic metabolism affects anti-tumour immunity and immunotherapy outcomes.

Fast facts

Cancer cells have hijacked for their own benefit the inflammatory processes that help support wound healing of normal tissues.

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A gene or protein which is identified to cause, or play a major role, in the disease.

A drug which attacks a specific protein of the cancer. Such drugs therefore only work on cancer where such a protein confers a specific benefit for a particular cancer to grow and spread.

Recent publications

Mucosal Immunology

Role reversals: non-canonical roles for immune and non-immune cells in the gut

DOI: 10.1016/j.mucimm.2023.11.004

1 December 2023

View abstract
Trends in Cancer

Gut microbiota - a double-edged sword in cancer immunotherapy

DOI: 10.1016/j.trecan.2022.08.003

8 September 2023

View abstract
Clinical & Translational Immunology

Sex-bias in CD8+ T-cell stemness and exhaustion in cancer

DOI: 10.1002/cti2.1414

26 August 2022

View abstract

Our team

Meet our researchers

  • Jayendra Singh - PhD Student
  • Adelynn Tang - PhD Student
  • Jian Wu - PhD Student

Receptor Biology Laboratory

Our research focus

Eph receptors

Eph receptors are cell surface proteins that guide cell migration by binding to other cell-bound proteins (ephrins) on adjacent cells, thereby controlling cell-cell adhesion. Ephs coordinate cell movement during normal development of tissue and organ boundaries, and the vascular and neural networks. They are generally scarce in adults but reappear in cancers, where they are often on early ‘progenitor’ cell types, associated with blood vessel formation, and tumour cell invasion and spread.

EphA3 is a particular focus, which we investigate in tumour models, using ‘knock-down’ mice or by treatment with a specific antibody we helped develop, with the aid of drug payloads to specifically target the tumour microenvironment.

ADAM metalloproteases

ADAM metalloproteases (or ADAMs) are cell membrane-bound proteases that shed a range of other membrane proteins, regulating the activity of diverse cell surface receptors. These include Ephs and other receptors controlling cancer cell growth, drug resistance, and invasion and spread to other tissues. ADAMs also play an important role in the tumour microenvironment and in inflammation.

ADAM10 and 17 are of particular interest and we are investigating their function in tumours, as well as developing antibodies and antibody-drug conjugates as potential new therapies.

Fast facts

Cell surface (or membrane) receptors are proteins attached to a cell’s exterior which can receive external signals, usually by binding with another protein. The bound receptors then send signals into the cell to modify its behaviour, including movement, proliferation and survival.

They are distinctive in that they bind to proteins attached to adjacent cells. This allows them to control cell adhesion, migration and invasion. They are important in normal embryonic development but reappear in certain cell types in tumours and their surrounding environment, including new tumour blood vessels, which support tumour growth and spread.

A protease is a protein which cuts other proteins in a very controlled manner. ADAMs are a type of cell surface metalloprotease (‘metallo’ refers to their dependence on metal ions). ADAM10 and 17 control the activity of various cell surface receptors and are essential in normal cellular development. However they become overly active in tumours and their surrounding environment by supporting tumour growth, survival and drug resistance.

Recent publications

Cancers

Inhibition of EphA3 Expression in Tumour Stromal Cells Suppresses Tumour Growth and Progression

DOI: 10.3390/cancers15184646

20 September 2023

View abstract
Biomed Pharmacotherapy

Fully human monoclonal antibody targeting activated ADAM10 on colorectal cancer cells

DOI: 10.1016/j.biopha.2023.114494

12 March 2023

View abstract
Biomedicines

Eph Receptors in Cancer

DOI: 10.3390/biomedicines11020315

23 January 2023

View abstract

Our team

Meet our researchers


Tumour Targeting Laboratory

Our research focus

Targeting Strategies in Cancer

We have identified a series of molecules selectively expressed on cancer cells, and in the tumour microenvironment, that can be targeted for cancer therapy. This includes conformationally exposed receptor epitopes, such as found on the Epidermal Growth Factor Receptor (EGFR) and which led to the development of mAb806 and our first-in-human trials of this molecule. Our research findings have provided a new paradigm in antibody-based targeting and therapy of solid tumours. This work has expanded to incorporate structure-function studies of additional novel antibodies we have developed that target cell surface receptors and tumour microenvironment in tumours, as well as investigating mechanisms of resistance to antibody therapeutics, and targeting key molecules involved in sustaining the tumour microenvironment.

Antibody Engineering

We have developed techniques for generation and humanisation of antibodies. Recent molecular engineering, structural and modelling approaches in our laboratory have defined novel Fc:FcRn and Fc:FcγR interactions, which result in improved immune effector function and bioavailability of humanised antibodies. We have also developed strategies to deliver payloads specifically to tumours through conjugation of drugs, toxins and isotopes to recombinant antibodies, peptides and nanoparticles, both in preclinical models and more recently in clinical trials in cancer patients. These studies are showing encouraging results in patients with cancers of the brain, colon and breast, as well as other solid tumours.

Tumour Payload Delivery

The development of recombinant antibodies for cancer therapy has emerged as one of the most promising areas in oncology therapeutics, both as single agents, and for payload delivery. The concept of being able to deliver toxins through antibody-drug conjugates, or radiotherapy by antibody-radioisotope conjugates targeting the payload to sites of disease, are exciting and promising approaches that we are exploring preclinically and clinically with antibodies developed in our laboratory.

Novel Metabolic Tracers

An exciting recent development in the molecular imaging of cancer comes from the identification of critical biochemical pathways responsible for tumour growth and metastasis, and immune targets which can be exploited for therapy, which can be imaged with novel SPECT and positron emission tomography (PET) tracers. Taking the discovery of novel metabolic tracers in the laboratory to clinical trials is a major focus of our molecular imaging / PET research program and is leading to a deeper understanding of tumour biology and therapy response.

Fast facts

An immune protein normally produced within the body, that can recognise and eliminate foreign substances that can cause tissue damage.

Cancer scientists are able to develop and introduce antibodies into the body. They can be designed to recognise and target a specific feature of the tumour to inhibit or stop tumour growth.

Molecular imaging technologies which allow researchers to see whether treatments are effectively targeting a tumour, and how a tumour responds to treatment.

Recent publications

European Journal of Nuclear Medicine and molecular imaging

FDG-PET/CT for investigation of pyrexia of unknown origin: a cost of illness analysis

DOI: 10.1007/s00259-023-06548-y

7 December 2023

View abstract
The Lancet Oncology

Overall survival with [177Lu]Lu-PSMA-617 versus cabazitaxel in metastatic castration-resistant prostate cancer (TheraP): secondary outcomes of a randomised, open-label, phase 2 trial

DOI: 10.1016/S1470-2045(23)00529-6

30 November 2023

View abstract
Frontiers Oncology

Clinical and research updates on the VISTA immune checkpoint: immuno-oncology themes and highlights

DOI: 10.3389/fonc.2023.1225081

15 September 2023

View abstract

Our team

Meet our researchers

  • Prof Andrew Scott AM - Head, Tumour Targeting Program | Head, Tumour Targeting Laboratory | Co-Director, Centre for Research Excellence in Brain Cancer | Director, Department Of Molecular Imaging And Therapy, Austin Health | Head, ACRF Centre for Precision Medicine  Publications
  • Prof Hui Gan - Clinical Research Lead | Clinician Scientist | Co-Director, Centre for Research Excellence in Brain Cancer | Director, Cancer Clinical Trials Centre, Austin Health  Publications
  • Zhanqi Liu - Associate Investigator
  • Ingrid Burvenich - Senior Research Scientist  Publications
  • Christian Wichmann - Senior Research Scientist Publications
  • Sagun Parakh - Clinician Scientist | Postdoctoral Research Fellow Publications
  • Sweet Ping Ng - Honorary Clinician
  • Eliza Hawkes - Clinician Scientist Publications
  • Laura Osellame - Postdoctoral Research Fellow Publications
  • Zhipeng Cao - Postdoctoral Research Fellow
  • Benjamin Gloria - Senior Cell Culture Scientist Publications
  • Angela Rigopoulos - Senior Research Officer Publications
  • Diana Cao - Senior Research Officer
  • Laura Allan - Senior Research Officer
  • Nancy Guo - Senior Research Officer Publications
  • Nhi Huynh - Senior Research Officer
  • Aidan Seow - Research Assistant
  • Fiona Scott - Program Manager Publications
  • Jodie Palmer - Lymphoma Program Manager
  • Kerryn Westcott - Scientific Project Officer | Student Administrator, School of Medicine LTU Publications
  • Clare Senko - PhD Student
  • Sadia Quazi - PhD Student
  • Siddharth Menon - PhD Student
  • Eng-Siew Koh - Honorary Clinician Publications
  • Farshad Foroudi - Honorary Clinician Publications
  • Michael Chao - Honorary Clinician
  • Michael McKay - Honorary Clinician Publications
  • Raef Boktor - Honorary Clinician
  • Richard Khor - Honorary Clinician
  • Stephen Chin - Honorary Clinician
  • Sze Ting Lee - Honorary Clinician
  • Henry Bom - Honorary Visiting Professor
  • Alexander McDonald - Honorary Publications
  • Arina Martynchyk - Honorary
  • Cameron Johnstone - Honorary
  • George Ferenzci - Honorary
  • Kunthi Pathmaraj - Honorary
  • Nick Hoogengraad - Honorary
  • Ryan Gillis - Honorary
  • Uwe Ackermann - Honorary
  • Haylee Lechner - Student Subject Placement

Cancer Single Cell Genomics Laboratory

Our research focus

Our goal is to understand cancer at a single cell level to advance cancer biomarker discovery and translation

Our laboratory specialises in using innovative single cell techniques to deconstruct tissue samples and reveal the genetic architecture of individual cells. This allows us to study heterogeneity in a range of cancers, including breast cancer, and address key biological questions:

  • How intra-tumoural heterogeneity drives tumour progression and metastasis in aggressive cancers?
  • What role do the tumour microenvironment play during metastasis?
  • How can we effectively monitor metastatic disease progression and prevent cancer recurrence?
  • Which premalignant molecular alterations are involved in breast tumorigenesis and can rare aberrant cell populations be identified for target biomarker discovery?
  • How single cell transcriptomics can be utilised to improve personalised treatment for cancer patients?

Fast facts

Metastasis refers to a disease stage when cancer cells break away and spread beyond the primary tumour to distant sites, with variable locations and volumes of organ involvement.

Created by a dynamic micro-community of cancer cells and surrounding blood, immune and stromal cells. Interactions between resident cell types can influence tumour progression and patient response to cancer treatment.

Recent publications

Life Science Alliance

Mechanisms of cellular crosstalk in the gastric tumor microenvironment are mediated by YAP1 and STAT3

DOI: 10.26508/lsa.202302411

13 November 2023

View abstract
Nature Communications

A tuft cell - ILC2 signaling circuit provides therapeutic targets to inhibit gastric metaplasia and tumor development

DOI: 10.1038/s41467-023-42215-4

28 October 2023

View abstract
CLINICAL AND TRANSLATIONAL MEDICINE

Single-cell RNA sequencing captures patient-level heterogeneity and associated molecular phenotypes in breast cancer pleural effusions

DOI: 10.1002/ctm2.1356

10 September 2023

View abstract

Our team

Meet our researchers

  • Dr Bhupinder Pal – Head, Cancer Single Cell Genomics Laboratory Publications
  • Chamikara Liyanage - Postdoctoral Research Fellow
  • Shalini Guleria - Honorary
  • Rebecca Brown - PhD Student
  • Liam Neil - PhD Student
  • Kurtis Green - Honours Student

Tumour Progression and Heterogeneity Laboratory

Our research focus

Isolation and characterisation of circulating tumour cells

Liquid biopsies, which capture circulating tumour cells in the blood, are a useful, non-invasive way of monitoring tumour spread and drug response. Our laboratory studies the diversity and biological properties of cancer cells captured in blood. This helps improve the diagnosis of patients, predict drug response and, in the longer term, develop cancer treatments personalised to a patient’s specific cancer.  

Follow tumour progression using cellular tracking

Each cell collected from a patient’s tumour can be labelled with tags or ‘barcodes’, allowing us to determine which subpopulations of cells in the tumour contribute to metastasis, organ specificity and drug-resistance. We are particularly interested in the effect of different microenvironments or ‘niches’ on the survival of cancer cells and the progression of disease.

Test new drugs in advanced models of metastatic breast cancer

Our laboratory is interested in developing ways to test the effect of various drugs on the survival of circulating tumour cells or metastasis. In particular, we focus on testing the effect of new targeted therapies on metastatic progression.

Fast facts

Some cancer cells have the ability to spread in the body. They can invade locally to nearby lymph nodes, to the vasculature and distant organs. This process is called metastasis. The mechanisms by which cells are able to adapt to different microenvironment are still unknown, but it appears that only a few cells from a tumour will successfully grow in distant organs and cause symptoms.

Different tumour cells in a tumour can show distinct phenotypic profiles such as gene expression, proliferation, and metastatic potential.

Drugs which specifically block the proliferation, survival or invasiveness of cancer cells, by targeting specific cellular pathways.

Recent publications

Clinical & Translational Medicine

Single-cell RNA sequencing captures patient-level heterogeneity and associated molecular phenotypes in breast cancer pleural effusions

DOI: 10.1002/ctm2.1356

10 September 2023

View abstract
Communications Biology

Experimental and spontaneous metastasis assays can result in divergence in clonal architecture

DOI: 10.1038/s42003-023-05167-5

7 August 2023

View abstract
Nature Reviews Cancer

Mastering the use of cellular barcoding to explore cancer heterogeneity

DOI: 10.1038/s41568-022-00500-2

18 August 2022

View abstract

Our team

Meet our researchers

  • A/Prof Delphine Merino - Head, Tumour Progression and Heterogeneity Laboratory Publications
  • Jean Berthelet - Senior Postdoctoral Research Fellow Publications
  • Yunjian Wu - Postdoctoral Research Fellow
  • Farrah El-Saafin - Senior Research Assistant Publications
  • Caroline Bell - Research Assistant
  • Sreeja Gadipally - PhD Student
  • Sam Lee - PhD Student
  • Andrew Li - PhD Student
  • Eleanor Ritchie - PhD Student
  • Shakiba Momeni - Honours Student

Bioinformatics and Cancer Genomics Laboratory

Our research focus

Develop a novel method for quantifying scRNA-seq data.

Single-cell RNA sequencing (scRNA-seq) has transformed the field of biomedical research. The 10x Genomics scRNA-seq technology is capable of sequencing the expression of thousands of genes in hundreds of thousands of individual cells simultaneously. Quantifying UMI (Unique Molecular Identifier) data generated from this technology is challenging because of the large volume of the data and the complexity of quantification. We are developing a new algorithm for accurate and efficient quantification of data from this technology. The successful development of this new bioinformatics tool will significantly reduce the data analysis time and improve the accuracy of gene expression quantification.

Develop a new method for mapping long sequencing reads

Long-read sequencing technologies, such as Nanopore and PacBio, have the potential to sequence whole gene transcript and discover long-range genomic mutations among other applications. A significant challenge for analysing long-read data is the read mapping which aligns each read to a reference genome. This is a critical step for successfully identifying full gene transcripts and detecting breakpoints of long-range mutations. We will expand the ‘seed-and-vote’ read mapping paradigm we successfully developed for mapping short reads, to develop a new method for long-read mapping. The successful development of this new tool is likely to result in discovery of new gene transcripts and mutations in diseases such as cancer.

Reconstruct a gene regulatory network to elucidate the differentiation of CD8+ T cells

Understanding the molecular mechanisms underlying the differentiation of CD8+ T cells will not only generate new knowledge in the field of immunity but is also important for the development of new strategies for improved immunotherapy. We will utilise omics data generated for mouse with chronic infection to reconstruct a gene regulatory network (GRN) containing interaction of key transcription factors and target genes to elucidate how differentiation of CD8+ cells are delicately regulated. We will then investigate how this GRN is perturbed in metastatic breast cancer using a mouse model of this disease and also cancer patient sequencing data available in the The Cancer Genome Atlas (TCGA) database. An outcome of this study will be a gene signature that can be used to predict which metastatic breast cancer patients will respond to immunotherapy.

Provide bioinformatics support to biology labs

Modern biomedical research makes use of powerful sequencing technologies such as single-cell RNA sequencing technologies. Bioinformatics support for fast and accurate analysis of sequencing data is important for the success of such research. Our lab collaborates with almost all the labs at ONJCRI to provide strong support for their bioinformatics needs. We specialize in analysing data generated from a range of sequencing technologies including bulk RNA-seq, single-cell RNA-seq, single-cell TCR-seq, ChIP-seq, ATAC-seq etc. We are also experienced in analysing public datasets generated by large consortia such as TCGA. We have contributed to many discoveries made in projects related to a wide range of cancer such as GI cancer, breast cancer and brain cancer.

Fast facts

An inter-disciplinary field that involves computer science, mathematics, genomics and biology. Computing scientists develop algorithms and software tools to analyse genomics data that are usually in a large scale, including genome-wide molecular data such as gene expression data, mutation data, transcription factor binding data and chromatin accessibility data.

Cancer genomics is the study of the molecular changes that occur in a cancer genome. It provides a powerful approach for detecting new genes and mutations  of cancer in a very time-efficient manner.

A sequencing technology that  enables the discovery of genes, digitally, that may be turned on or off in diseases such as cancer.

A graph in which nodes represent genes and edges represent interactions. The interaction can be direct or indirect. A direct interaction is a physical interaction that for example can be DNA binding or phosphorylation. An indirect interaction is usually co-expression of two genes. In a gene regulatory network, a gene may interact with two or more genes.

Recent publications

Nucleic Acids Research

Dividing out quantification uncertainty allows efficient assessment of differential transcript expression with edgeR

DOI: 10.1093/nar/gkad1167

7 December 2023

View abstract
Life Science Alliance

Mechanisms of cellular crosstalk in the gastric tumor microenvironment are mediated by YAP1 and STAT3

DOI: 10.26508/lsa.202302411

13 November 2023

View abstract
Nature Communications

A tuft cell - ILC2 signaling circuit provides therapeutic targets to inhibit gastric metaplasia and tumor development

DOI: 10.1038/s41467-023-42215-4

28 October 2023

View abstract

Our team

Meet our researchers

  • Prof Wei Shi - Head, Bioinformatics and Cancer Genomics Laboratory Publications
  • Yang Liao - Postdoctoral Research Fellow
  • David Chisanga - Honorary

Metastasis Research Laboratory

Our research focus

We have identified several genes that regulate the metastatic process. By understanding how these genes act to control metastasis, we can develop effective therapies which directly target these genes or other genes controlled by these metastasis regulators. Another important aspect of our research is to examine human breast cancer tissues for evidence that the gene identified in our preclinical models is also relevant in the human disease.

Metastasis Regulating Genes

We have shown that some of the genes we have identified, including caveolin-1, microRNA-200 and BMP4, are able to suppress metastasis. With BMP4, we have found that its metastasis suppressing activity is in part through the inhibition of G-CSF, which controls the mobilisation and differentiation of neutrophils. In the presence of a tumour, the activity of neutrophils can be changed from infection fighting to supporting the spread of cancer cells to other organs, such as the lung. This led to our demonstration in our preclinical models that blocking the mobilisation of neutrophils can reduce metastasis. We are now probing more deeply to understand how neutrophil function is altered by factors released from tumours and the relevance of this to patients with breast cancer.

Much of our research is focused on immune regulation of metastasis by the innate immune system (including macrophages and neutrophils), but some of the other genes we have identified appear to act directly on the tumour cells to prevent their ability to metastasise.

Metastatic Dormancy

Breast cancer is noted for the long latency between diagnosis and therapy for the primary cancer and development of secondary cancers, which can cause ongoing anxiety for patients fearing a recurrence. We are investigating how tumour cells can disseminate from the primary tumour and remain alive but clinically undetectable for many years, and how they start expanding into life-threatening cancers in some patients. We are seeking therapies that prevent the expansion of these dormant cancer cells into new tumours.

Drug Discovery and Delivery

We have collaborated with Dr Ian Street and the Walter and Eliza Hall Institute drug discovery team to identify small molecules that can be developed into drugs to combat metastatic disease. We also work with the ARC Centre of Excellence in Convergent Bio-Nano Science and Technology (Monash University) to improve drug delivery to tumours using nanoparticle technology.

Fast facts

More than 18,000 Australian women and about 150 men were diagnosed with breast cancer in 2019 and more than 3,200 died, largely due to their cancer spreading to other vital organs such as the liver, lung and brain.

The process by which cancer cells spread from one organ to another, forming secondary tumours. Breast cancer commonly spreads to bone, liver, lung and brain.

A common type of white blood cell. They are an important part of the immune system and are found in sites of inflammation. They are the first line of defence against infectious agents but they can also contribute to the growth and spread of tumours.

A nanometre is one billionth of a metre, which means nanoparticles are small enough to move through the bloodstream. Nanotechnology can deliver drugs to specific cells, such as tumour cells, reducing the chances of adverse reactions in the patient.

Recent publications

Cancers

Inhibition of EphA3 Expression in Tumour Stromal Cells Suppresses Tumour Growth and Progression

DOI: 10.3390/cancers15184646

20 September 2023

View abstract
Clinical and Translational Medicine

Single-cell RNA sequencing captures patient-level heterogeneity and associated molecular phenotypes in breast cancer pleural effusions

DOI: 10.1002/ctm2.1356

10 September 2023

View abstract
Journal of Experimental & Clinical Cancer Research

COMMD3 loss drives invasive breast cancer growth by modulating copper homeostasis

DOI: 10.1186/s13046-023-02663-8

18 April 2023

View abstract

Our team

Meet our researchers

  • Caroline Bell - Research Assistant
  • Judy Borg - Research Assistant
  • Simon Tsao - Honorary
  • Tom Elliott - Honours Student

Cell Death and Survival Laboratory

Our research focus

Apoptosis

Cellular fate is controlled by multiple molecular pathways. The most studied is apoptosis, a form of programmed cell death used by all multicellular organisms to eliminate cells which are damaged, no longer needed or which might become a threat to the organism. This process is often deregulated in cancer cells allowing them to survive and proliferate when otherwise they should be eliminated.

BH3 mimetics

Dysfunctional apoptosis can cause or accelerate cancer development, but also underlies resistance to common cancer treatment approaches such as chemotherapy. Members of a particular family of proteins (the “BCL-2” proteins) are critical regulators of apoptosis. Recently, a new class of drugs called “BH3 mimetics” have been developed to target some BCL-2 proteins and activate apoptosis, leading to tumour cell death. One of these drugs is now being used in the clinic to treat some blood cancers, and others are under extensive investigation, including by our lab.

Autophagy

Autophagy is predominantly a process that enables cells to survive under stressful conditions such as when nutrients are in short supply. Like apoptosis, it can also become dysfunctional in cancer. Under some circumstance, proteins that regulate autophagy can also interact with those involved in apoptosis. This is a particular interest of our lab as it might have important implications for how cancer cells survive abnormally, and also for the normal functioning of tissues such as the gut.

Fast facts

This term encompasses events such as when a cell receives external cues (e.g. from factors like proteins in the blood) and transmits them inside the cell to activate processes such as cell division, movement and death. Cells can also signal to other cells by secreting molecules such as proteins.

Under normal conditions,  apoptosis is essential to remove old, damaged or dangerous cells. In cancer, this process is often switched off allowing abnormal cells to survive and grow when they should otherwise be killed and eliminated.

Primarily, a cell survival process meaning to “self eat”. In times of stress, nutrient deprivation or infection, the cell eats its own components in order to maintain cellular energy levels, or to remove unwanted materials (such as viruses and non-functioning protein aggregates) allowing it to survive.

Recent publications

Cancer Medicine

Induction of endoplasmic reticulum stress is associated with the anti-tumor activity of monepantel across cancer types

DOI: 10.1002/cam4.6021

6 May 2023

View abstract
Biochemical Society Transactions

The emerging roles of autophagy in intestinal epithelial cells and its links to inflammatory bowel disease

DOI: 10.1042/BST20221300

13 April 2023

View abstract
Cell Death Discovery

A novel BH3-mimetic, AZD0466, targeting BCL-XL and BCL-2 is effective in pre-clinical models of malignant pleural mesothelioma

DOI: 10.1038/s41420-021-00505-0

28 May 2021

View abstract

Our team

Meet our researchers

  • Samson Dsouza - Masters Intern
  • Josje Ketels - International Intern
  • Ella Van Zuijlen - Honours Student