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
  • Sze Ting Lee - Clinician Scientist
  • 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
  • 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

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

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

  • Caroline Bell - Research Assistant
  • Sreeja Gadipally - PhD Student
  • Sam Lee - 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
  • Jennifer Snowball - PhD Student

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

  • Charlotte Roelofs - Postdoctoral Research Fellow Publications
  • Caroline Bell - Research Assistant
  • Judy Borg - Research Assistant
  • Simon Tsao - Honorary

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


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

American Journal of Physiology

Intestinal-specific Hdac3 deletion increases susceptibility to colitis and small intestinal tumor development in mice fed a high-fat diet

DOI: 10.1152/ajpgi.00160.2023

6 November 2023

View abstract
Molecular Cancer Therapeutics

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
Cell Death & Differentiation

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, Oncogenic Transcription Laboratory Publications
  • Fiona Chionh - Clinician Scientist | Postdoctoral Research Fellow  Publications
  • Niall Tebbutt - Clinician Scientist (Honorary)
  • David Williams - Clinician Scientist (Honorary)
  • Ian Luk - Research Scientist Publications
  • Kaveh Baghaei - Postdoctoral Research Fellow
  • Laura Jenkins - Postdoctoral Research Fellow
  • Camilla Reehorst - Postdoctoral Research Fellow
  • Rebecca Nightingale - Research Assistant
  • Stan Kacmarczyk - Honorary
  • David Lau - Honorary
  • Kristen Needham - PhD Student
  • Charles Uy - PhD Student
  • Natalia Vukelic -  PhD Student
  • Jamieson Ayton - Honours Student
  • Jack Collin - Honours Student

Mucosal Immunity and Cancer Laboratory

Our research focus

Function of intestinal immune cells in bowel cancer

Intraepithelial lymphocytes (IELs) are immune cells which continually survey intestinal epithelial cells for infection or damage. Bowel cancer forms when the epithelial cells become damaged and change, growing in an uncontrolled manner. The role of IELs in this process, and whether or not they play a role in tumour cell growth or killing tumour cells, has not been studied in detail. Our laboratory aims to understand these cells, including the molecules that regulate their function in steady state development and in the development of cancer. 

Regulation of cytokines in the gastrointestinal tract

Cytokines, such as IL-17 and IL-22, are secreted by immune cells and are critical in boosting epithelial cell and tumour survival in the intestine. Bowel cancer patients with increased IL-17 and IL-22 levels experience increased tumour growth and have a poorer prognosis. We are dissecting the molecular pathways and cell types involved in regulating IL-17 and IL-22 production to investigate the role these cytokines play in bowel cancer progression. It is crucial that we understand these mechanisms so we can develop new immune cell-mediated therapies to treat gastrointestinal cancers.

Influence of the microbiome on immune health  

Each person’s microbiome is unique and is made up of good bacteria, viruses and fungi which live on the body’s surfaces, such as the skin and intestine. Our understanding of these resident microbes and how they affect the body’s immune response to an infectious organism or disease, such as cancer, is limited. We are working to understand the mechanisms which link the microbiome to overall immune cell health, including the activation of transcription factors that guide immune cell development, as well as the cytokines they secrete in order to communicate with the rest of the body’s cells.

Fast facts

As well as being found in the blood, immune cells are also in the body’s tissues, which they continuously survey for infection and cancer.

Mucus-covered tissues including the lungs and gastrointestinal tract. These sites are home to specialised immune cells, which play a critical role in maintaining mucosal surfaces in order to protect the body from the external environment.

All the bacteria and other microbes that live on the body’s surfaces, such as the skin and intestine. Interaction between these microbes and immune cells is critical in shaping the immune system, and can even influence the body’s response to some cancer treatments.

Latest lab newsSupport Dr Lisa Mielke's bowel cancer research

Recent publications

Science

Divergent molecular networks program functionally distinct CD8+ skin-resident memory T cells

DOI: 10.1126/science.adi8885

30 Nov 2023

View abstract
Science Immunology

TCF-1 limits intraepithelial lymphocyte antitumor immunity in colorectal carcinoma

DOI: 10.1126/sciimmunol.adf2163

6 October 2023

View abstract
Bioinformatics

CellCounts: an R function for quantifying 10x Chromium single-cell RNA sequencing data

DOI: 10.1093/bioinformatics/btad439

18 July 2023

View abstract

Our team

Meet our researchers

  • Dr Lisa Mielke - Head, Mucosal Immunology Laboratory Publications
  • Kelly Tran - Research Assistant
  • Chloe Jackson - PhD Student
  • Pavitha Parathan - PhD Student
  • Marina Yakou - PhD Student
  • Katherine Eljammas - Honours Student

Tumour Immunology Laboratory

Our research focus

We constantly use and develop cutting-edge methodologies, including multiplex immuno-fluorescence and RNA-Scope for the characterisation of the tumour microenvironment, protein arrays for the detection of cancer-specific antibodies, and in vitro T cell assays for the detection of novel immunogenic peptides, among others. We are exploring how a successful immune recognition is orchestrated and translated from the early (innate arm) to the late (adaptive) response.

This ‘immunostaging’ of cancers will allow us to understand why and how immunotherapy works for some patients but not for others, and how we can increase the number of patients who benefit from these treatments. The laboratory has extensive experience in clinical trial monitoring and collaborative industry projects, all centred on improving outcomes and quality of life for cancer patients. We collaborate with several leading cancer research laboratories in Australia and internationally.

Fast facts

Tumour cells often look very different to the immune system when compared to healthy cells. To avoid destruction, tumours use a variety of strategies to overcome or to ‘hide’ from an immune response. This interaction of tumour cells with a large variety of immune cells can be more or less pronounced and influence outcome of the disease or response to particular treatments. The quality and quantity of these interactions can be measured on multiple levels, which all together represent the tumour-immune engagement.

Antibodies are proteins produced by a subtype of immune cells which can specifically recognise, bind and often neutralise antigens which the immune system recognises as foreign or a threat (e.g. viruses or bacteria). In cancer, specific antibodies are produced as a response to antigens on cancer cells, which are different than those on normal cells. While their function in the immune recognition of cancer is unclear, their detection in the blood indicates the presence of cancer cells.

Recent publications

Science Immunology

TCF-1 limits intraepithelial lymphocyte antitumor immunity in colorectal carcinoma

DOI: 10.1126/sciimmunol.adf2163

6 October 2023

View abstract
European Journal of Cancer

Durable response to combination immunotherapy using nivolumab and ipilimumab in metastatic succinate dehydrogenase (SDH)-deficient gastrointestinal stroma tumour

DOI: 10.1016/j.ejca.2023.113351

22 September 2023

View abstract
STAR Protocols

Protocol for investigating tertiary lymphoid structures in human and murine fixed tissue sections using Opal™-TSA multiplex immunohistochemistry

DOI: 10.1016/j.xpro.2022.101961

17 March 2023

View abstract

Our team

Meet our researchers

  • Luke Quigley - Research Assistant
  • Farzeneh Atashrazm - Honorary
  • Devi Dharmaraj - Honorary
  • Damien Kee - Honorary
  • Kiet Nguyen - Student Subject Placement
  • Faiza Tabassum - Student Subject Placement

Tumour Microenvironment and Cancer Signaling Group

Our research focus

DCLK1

DCLK1 is a microtubule-associated protein which catalyses the polymerisation of tubulin dimers. This process is critical in the formation of microtubules, a major component of the cellular cytoskeleton, and also important in many cellular functions such as cell division and migration. DCLK1 expression is excessively upregulated in various types of cancer and, pertinently, high DCLK1 expression is significantly correlated with poorly differentiated cancers, lymph node metastasis, advanced clinical stage, and poorer overall patient survival, suggesting that the overexpression of DCLK1 may accelerate cancer development.

Tuft cells

A structurally unique cell type, best characterised by striking microvilli which form an apical tuft. These cells represent approximately 0.5% of tissue epithelial cells depending on location. Tuft cells act as luminal sensors, linking the luminal microbiome to the host immune system, which may make them a potent clinical target for modulating host response to a variety of acute or chronic immune-driven conditions.

Our lab is using powerful single-cell sequencing approaches and has developed experimentally tractable tools in order to interrogate this rare cell population, with the aim of unravelling its physiological importance in inflammation-driven gastrointestinal diseases, such as colon and gastric cancers.

Innate lymphoid cells

These cells are a newly discovered type of innate immune cell which resemble lymphocytes but lack a T cell receptor. They are predominantly found in mucosal surfaces associated with epithelial tissues, such as the gut, lung and skin, and have important roles in immunity, infection and homeostasis. Our lab is investigating the interplay between Tuft cells and ILC2 cells during gastric homeostasis and cancer.

Fast facts

The cellular environment within which the tumour exists. This includes the surrounding blood vessels, immune cells, fibroblasts, bone marrow-derived inflammatory cells, lymphocytes, signalling molecules and the extracellular matrix (ECM).

Rare chemosensory cells scattered throughout the epithelium tissue of the digestive tract. Their biological functions include tissue repair and regeneration, as well as modulation of immune responses during parasite infections. Tuft cell numbers increase during the early stages of tumour development. The importance of this increase is not yet well understood.

They play a crucial role of secreting type 2 cytokines in response to certain parasitic infections. They have also been implicated in the development of allergic lung inflammation. They express characteristic surface markers and receptors for chemokines, which are involved in distributing lymphoid cells to specific organ sites. ILC2s are critical in primary responses to local Th2 antigens, such as helminths and viruses, and is why they are abundant in tissues of the skin, lungs, liver and gut. Their role in cancer development is not yet well understood.

The epithelial–mesenchymal transition (EMT) is a process through which epithelial cells lose their cell polarity and intercellular adhesion, instead gaining migratory and invasive properties to become mesenchymal stem cells, which are multipotent stromal cells that can differentiate into a variety of different cell types.

Recent publications

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
Biomedicines

Structure-Guided Prediction of the Functional Impact of DCLK1 Mutations on Tumorigenesis

DOI: 110.3390/biomedicines11030990

22 March 2023

View abstract
Frontiers

Crosstalk between epithelium, myeloid and innate lymphoid cells during gut homeostasis and disease

DOI: 10.3389/fimmu.2022.944982

16 September 2022

View abstract

Our team

Meet our researchers

  • Ryan O'Keefe - Postdoctoral Research Fellow Publications
  • Birhanu Ayelign Jemere - PhD Student
  • Kiruthiga Raghunathan - PhD Student
  • Rokaya Rehouma - PhD Student