Blood Cancer and Immunotherapy Lab

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

Nature

Deletion of the transcriptional regulator TFAP4 accelerates c-MYC-driven lymphomagenesis

DOI: 10.1038/s41418-023-01145-w

9 March 2023

View abstract
Frontiers

An arrayed CRISPR screen of primary B cells reveals the essential elements of the antibody secretion pathway

DOI: 10.3389/fimmu.2023.1089243

13 February 2023

View abstract
EMBO Press

Caspase-8-driven apoptotic and pyroptotic crosstalk causes cell death and IL-1β release in X-linked inhibitor of apoptosis (XIAP) deficiency

DOI: 10.15252/embj.2021110468

17 January 2023

View abstract

Our team

Meet our researchers

  • Prof Marco Herold - Head, Blood Cancer and Immunotherapy Lab Publications
  • Dr Andrew Kueh - Platform Lead
  • Emily Lelliott - Postdoctoral Research Fellow


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

AARC

CDK4/6 Inhibition Promotes Antitumor Immunity through the Induction of T-cell Memory

DOI: 10.1158/2159-8290.CD-20-1554

1 October 2021

View abstract
Science Advances

SUGAR-seq enables simultaneous detection of glycans, epitopes, and the transcriptome in single cells

DOI: 10.1126/sciadv.abe3610

19 February 2021

View abstract
Science Advances

Tumor immune evasion arises through loss of TNF sensitivity

DOI: 10.1126/sciimmunol.aar3451

4 May 2018

View abstract

Our team

Meet our researchers

  • Dr Conor J Kearney - Head, Molecular Immunology Laboratory Publications
  • Ms Elizabeth Georges - Research Assistant
  • Mr Pengjin Wen – PhD student
  • Ms Lizzy Lijpers – PhD student
  • Tirta (Mario) Djajawi - Postdoctoral Research Fellow


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

Cell

Gut microbiota - a double-edged sword in cancer immunotherapy

DOI: 10.1016/j.trecan.2022.08.003

8 September 2022

View abstract
Wiley

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

DOI: 10.1002/cti2.1414

26 August 2022

View abstract
Nature

Resident and migratory adipose immune cells control systemic metabolism and thermogenesis

DOI: 10.1038/s41423-021-00804-7

26 November 2021

View abstract

Our team

Meet our researchers


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

MDPI

Preferential Antibody and Drug Conjugate Targeting of the ADAM10 Metalloprotease in Tumours

DOI: 10.3390/cancers14133171

28 June 2022

View abstract
Portland Press

The intracellular domains of the EphB6 and EphA10 receptor tyrosine pseudokinases function as dynamic signalling hubs

DOI: 10.1042/BCJ20210572

14 September 2021

View abstract
ARRC

Eph Receptors in the Immunosuppressive Tumor Microenvironment

DOI: 10.1016/j.xpro.2022.102021

15 Feb 2021

View abstract

Our team

Meet our researchers

  • A/Prof Peter Janes - Head, Receptor Biology Laboratory Publications
  • Stacey Allen - Senior Research Assistant
  • Mary Vail - Postdoctoral Research Fellow Publications
  • Hengkang Yan - PhD Student
  • Sakshi Arora - PhD Student


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

BioMed Central

Perspectives on joint EANM/SNMMI/ANZSNM practice guidelines/procedure standards for [18F]FDG PET/CT imaging during immunomodulatory treatments in patients with solid tumors

DOI: 10.1186/s40644-022-00512-z

20 December 2022

View abstract
Science Direct

18F-labeling and initial in vivo evaluation of a Hitomi peptide for imaging tissue transglutaminase 2

DOI: 10.1016/j.nucmedbio.2022.11.002

26 November 2022

View abstract
MDPI

Identification of Potential Biomarkers for Cancer Cachexia and Anti-Fn14 Therapy

DOI: 10.3390/cancers14225533

10 November 2022

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   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 - Postdoctoral Research Fellow Publications
  • Alexander Mcdonald - Postdoctoral Research Fellow Publications
  • Sagun Parakh - Postdoctoral Research Fellow Publications
  • Laura Osellame - Postdoctoral Research Fellow Publications
  • Benjamin Gloria - Senior Production Scientist Publications
  • Laura Allan - Senior Research Officer
  • Diana Cao - Senior Research Officer
  • Nancy Guo - Senior Research Officer Publications
  • Nhi Huynh - Senior Research Officer
  • Angela Rigopoulos - Senior Research Officer Publications

  • Eliza Hawkes - Clinician Scientist Publications
  • Umbreen Hafeez - PhD Student
  • Siddharth Menon - PhD Student
  • Fiona Scott - Program Manager Publications
  • Kerryn Westcott - Scientific Project Officer Publications
  • Uwe Ackermann - Senior Radiochemist, Department of Medical Imaging & Therapy, Austin Health (Honorary)
  • Farshad Foroudi - Director Radiation Oncology, Austin Health (Honorary) Publications
  • Sze-Ting Lee, Nuclear Medicine Physician, Department of Medical Imaging & Therapy, Austin Health (Honorary) Publications
  • Prof Michael McKay, Senior Researcher (Honorary) Publications
  • Sadia Quazi - PhD Student
  • Clare Senko - PhD Student


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

MDPI

Computational Screening of Anti-Cancer Drugs Identifies a New BRCA Independent Gene Expression Signature to Predict Breast Cancer Sensitivity to Cisplatin

DOI: 10.3390/cancers14102404

13 May 2022

View abstract
Nature

R code and downstream analysis objects for the scRNA-seq atlas of normal and tumorigenic human breast tissue

DOI: 10.1038/s41597-022-01236-2

23 March 2022

View abstract
Science

A diverse fibroblastic stromal cell landscape in the spleen directs tissue homeostasis and immunity

DOI: 10.1126/sciimmunol.abj0641

7 January 2022

View abstract

Our team

Meet our researchers

  • Dr Bhupinder Pal – Head, Cancer Single Cell Genomics Laboratory Publications
  • Paula Fuge-Larsen - Translational Research Project Officer
  • Shalini Guleria - PhD Student
  • Jordan Wilcox - Research Assistant
  • Rebecca Brown - PhD 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

Nature

Mastering the use of cellular barcoding to explore cancer heterogeneity

DOI: 10.1038/s41568-022-00500-2

18 August 2022

View abstract
MDPI

Computational Screening of Anti-Cancer Drugs Identifies a New BRCA Independent Gene Expression Signature to Predict Breast Cancer Sensitivity to Cisplatin

DOI: 10.3390/cancers14102404

13 May 2022

View abstract
Science Advances

The site of breast cancer metastases dictates their clonal composition and reversible transcriptomic profile

DOI: 10.1126/sciadv.abf4408

7 July 2021

View abstract

Our team

Meet our researchers


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

Red Journal

Microbeam Radiation Therapy Controls Local Growth of Radioresistant Melanoma and Treats Out-of-Field Locoregional Metastasis

DOI: 10.1016/j.ijrobp.2022.06.090

1 November 2022

View abstract
Nature

MicroRNA-21 is immunosuppressive and pro-metastatic via separate mechanisms

DOI: 10.1038/s41389-022-00413-7

11 July 2022

View abstract
MDPI

Computational Screening of Anti-Cancer Drugs Identifies a New BRCA Independent Gene Expression Signature to Predict Breast Cancer Sensitivity to Cisplatin

DOI: 10.3390/cancers14102404

13 May 2022

View abstract

Our team

Meet our researchers

  • Prof Robin Anderson - Head, Metastasis Research Laboratory | Co-Head, Cancer Biology and Therapy Program Publications
  • Belinda Yeo - Clinician Scientist Publications
  • Nil Ansari - Postdoctoral Research Fellow
  • Caroline Bell - Research Assistant
  • Allan Burrows - Postdoctoral Research Fellow Publications
  • Lap Hing (Leo) Chi - PhD Student
  • Bedrich Eckhardt - Postdoctoral Research Fellow Publications

  • Kellie Mouchemore - Postdoctoral Research Fellow Publications Publications
  • Richard Redvers - Postdoctoral Research Fellow Publications
  • Charlotte Roelofs - PhD Student
  • Suraya Roslan - Research Assistant
  • Victoria Simovich - Research Assistant
  • Stefan Bader - PhD 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 cell survive abnormally.

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

AARC

Genotype-Tailored ERK/MAPK Pathway and HDAC Inhibition Rewires the Apoptotic Rheostat to Trigger Colorectal Cancer Cell Death

DOI: 10.1158/1535-7163.MCT-22-0101

3 January 2023

View abstract
Portland Press

Targeting the BCL-2-regulated apoptotic pathway for the treatment of solid cancers

DOI: 10.1042/BST20210750

28 September 2021

View abstract
Portland Press

Discovery, development and application of drugs targeting BCL-2 pro-survival proteins in cancer

DOI: 10.1042/BST20210749

13 September 2021

View abstract

Our team

Meet our researchers

  • A/Prof Doug Fairlie - Head, Cell Death And Survival Laboratory  Publications
  • Erinna Lee - Visiting Scientist Publications
  • Tiffany Harris - Research Assistant
  • Nikita Steinohrt - Research Assistant
  • Sharon Tran - PhD Student


Oncogenic Transcription Laboratory

Our research focus

Epigenetic Therapy

We have found that a group of enzymes called histone deacetylases (HDACs) are required for colon cancer cell growth. We have also found that drugs which block these enzymes induce the differentiation and death of colon cancer cells. We are currently working on ways to further improve the anti-tumour activity of these drugs by combining them with existing therapies, in order to develop a new treatment for colon cancer patients.

Differentiation Therapy

Our laboratory also investigates the transcriptional mechanisms by which cellular and tissue differentiation is disturbed during colorectal tumorigenesis. We have identified a number of key transcription factors which are deregulated during this process, and we are using this information to investigate ways differentiation can be reprogrammed in tumour cells.

Discovery of biomarkers to targeted therapies

Through access to clinical trial samples provided by our long-term collaborator A/Prof Niall Tebbutt, our laboratory has a translational research program aimed at discovering the biomarkers predictive response to targeted therapies in gastrointestinal cancers. Agents we are investigating include anti-angiogenic therapeutics (avastin), EGFR inhibitors (cetuximab), BRAF inhibitors and mTOR inhibitors, in the treatment of colorectal cancer, gastric cancer and cholangiocarcinoma.

Fast facts

A small, functional unit of our DNA, containing the information, or “instructions” to produce other functional units, such as proteins.

The process the cell uses to transfer the information contained within the DNA into a format which can be used to inform the production of proteins.

Cancer is a genetic disease. When a gene is mutated, the gene may become unable to provide the right information and instructions to the proteins it informs. The cell is therefore unable to perform its proper job. This can lead to cancer.

Molecules consisting of amino acids, which the cells in the human body need to function properly. Each cell may have thousands of different proteins, each with its own instructions for that cell or those with which it interacts. When the proteins work together they ensure the cell does its job.

Recent publications

AARC

Genotype-Tailored ERK/MAPK Pathway and HDAC Inhibition Rewires the Apoptotic Rheostat to Trigger Colorectal Cancer Cell Death

DOI: 10.1016/j.xpro.2022.101961

3 January 2023

View abstract
Frontiers

Potentiating effect of reovirus on immune checkpoint inhibition in microsatellite stable colorectal cancer

DOI: 10.3389/fonc.2022.1018767

25 October 2022

View abstract
Nature

Epithelial de-differentiation triggered by co-ordinate epigenetic inactivation of the EHF and CDX1 transcription factors drives colorectal cancer progression

DOI: 10.1038/s41418-022-01016-w

23 May 2022

View abstract

Our team

Meet our researchers

  • Prof John Mariadason - Head, Gastrointestinal Cancers Program | Head, Oncogenic Transcription Laboratory Publications
  • Zakia Alam - PhD Student
  • Fiona Chionh - Postdoctoral Research Fellow  Publications
  • George Iatropoulos - PhD Student
  • Laura Jenkins - PhD Student
  • Stan Kacmarczyk - Senior Research Officer

  • Ian Luk - Postdoctoral Research Fellow Publications
  • Irvin Ng - Phd Student
  • Rebecca Nightingale - Research Assistant
  • Kael Schoffer - Research Assistant
  • Natalia Vukelic -  PhD Student
  • Kristen Needham - PhD Student
  • Charles Uy - PhD Student