Cancer and Inflammation Laboratory

Our research focus

We focus our research on three approaches to interfere with the communication between cancer and normal cells within a tumour.

Stat3 and tumourigenesis

Pronounced epithelial Stat3 activity is not only observed during wound-healing, but also in a majority of cancers including those in the colon, stomach, breast and lung. Our lab recently established a novel link, showing that the cytokine interleukin (IL)-11 – through its shared gp130 receptor, the associated Jak kinases and Stat3 signaling – promotes tumourigenesis. Surprisingly, this signaling cascade also becomes rate limiting for the growth of colon and gastric tumours that are driven by mutations in well recognised cancer pathways.

Neoplastic cells

We are therapeutically exploiting that neoplastic cells have often developed a higher dependency on a particular signal than their normal counterparts. For instance, oncogenic activation of the WNT/beta-catenin signaling cascade is the most common tumour-initiating event that occurs in epithelial stem cells and results in the development of sporadic colorectal cancer. Because interference with the gp130/Stat3 signaling cascades limits the expansion of such intestinal (cancer) stem cells, the addiction of colon cancer cells to gp130/Stat3 signaling can be therapeutically exploited in these tumours where targeting of the mutated WNT/beta-catenin signaling cascade is not feasible.

Hck activation

The cellular composition of the tumour microenvironment affects how well a tumour can grow and respond to targeted and immune-modulatory therapy. Although these processes are affected by many different cell types within the tumour stroma, macrophages and other myeloid-derived cells are among the most important players. We have found that the myeloid cell kinase Hck is highly abundant in the tumour microenvironment and aberrant Hck activation suppresses an effective anti-tumour immune response. We are therefore identifying ways by which we can most effectively target Hck to restore and augment anti-tumour immune responses to more effectively kill the cancer cells.

Fast facts

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

Within the tumour there are a number of cell types, both cancer cells and non-cancer cell types. This collective of different cell types is characterised by many molecular interactions that collectively determine how well a tumour responds to treatment.

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

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
Science Immunology

TCF-1 limits intraepithelial lymphocyte antitumor immunity in colorectal carcinoma

DOI: 10.1126/sciimmunol.adf2163

13 October 2023

View abstract

Our team

Meet our researchers

  • Prof Matthias Ernst - Head, Tumour Environment and Immunology Program |
    Head, Cancer And Inflammation LaboratoryPublications
  • David Baloyan - Flow Cytometry Operator Publications
  • Moritz Eissmann - Victorian Cancer Agency Research Fellow Publications
  • Shoukat Afshar-Sterle - Research Scientist Publications
  • Amr Allam - Postdoctoral Research Fellow Publications
  • Annalisa Carli - Postdoctoral Research Fellow
  • Anne Huber - Postdoctoral Research Fellow
  • Ryan O'Keefe - Postdoctoral Research Fellow
  • Megan O'Brien - Research Assistant
  • Saumya Parambate Jacob - Research Assistant
  • Gangadhara Gangadhara - Honorary  Publications
  • Ashleigh Poh - Honorary Publications
  • Purva Trivedi - PhD Student
  • Marina Yakou - PhD Student

Our Research

Our research programs focus on developing treatments for a range of cancers including breast, bowel and gastrointestinal tract, liver, lung, skin and brain cancer.

GENOME ENGINEERING AND CANCER MODELLING PROGRAM

Program Head: Prof Marco Herold

The Genome engineering and Cancer Modelling Program was recently established to develop new CRISPR models and methodologies, such as activating and base editing tools to understand how cancers develop and how we can use this information to develop better therapies. In addition, we use our genome engineering capacity to develop pre-clinical models to more accurately resemble human disease to trial newly identified therapies.

Find out more about the laboratories within the Genome Engineering and Cancer Modelling Program:

Blood Cancer and Immunotherapy Lab Prof Marco Herold

TUMOUR ENVIRONMENT AND IMMUNOLOGY PROGRAM

Program Head: Prof Matthias Ernst

Understanding how normal cells in the body can become corrupted by tumour cells is critical in order to stop the growth and spreading of cancers.

Many of the molecular processes that cancer cells use to communicate with normal cells also play important roles during wound-healing.

Therefore, cancer cells often hijack some of these mechanisms in order to survive, grow, obtain a steady stream of nutrients and develop resistance to treatment.

Our Cancer and Inflammation Program aims to better understand how cancer cells and normal cells communicate with each other within the tumour environment.

If we can disrupt these lines of communication, cancer cells will be more vulnerable as they become less supported by the normal cells in their vicinity.

Importantly, this strategy may also help make tumour cells more visible to immune cells and therefore more vulnerable to treatment with contemporary immune-based therapies.

While the activities of our Program focus primarily on cancers of the bowel, stomach and breast, many of these molecular communication mechanisms are also found in other solid tumours.

CANCER BIOLOGY AND THERAPY PROGRAM

Co-Program Heads: Prof John Mariadason, Prof Robin Anderson

The Cancer Biology and Therapy Program brings together six research groups focused on discovering the genetic and immunological regulators of cancer initiation, de-differentiation, metastasis, and survival, particularly in breast and gastrointestinal cancers, and harnessing this knowledge to improve the treatment of patients affected by these cancers.

We address these questions using cutting edge technologies including high throughput molecular and optical cell tracking strategies, single cell genomics, CRISPR and drug-screens and genetically modified mouse models and organoid systems.

We actively seek to translate our discoveries into the clinic by developing biomarkers that allow more personalised treatment for individual patients. Through the initiation of new clinical trials with our team of clinician-scientists, we seek to overcome resistance to cell death, prevent the migration of tumour cells, effectively control metastatic disease and activate the host’s immune system to attack cancer cells.

Therefore, the insights gained from our research could ultimately be translated to many different solid malignancies.

TUMOUR TARGETING PROGRAM

Program Head: Prof Andrew Scott AM

The Tumour Targeting Program focuses on the targeting, molecular imaging and treatment of tumours, as well as defining receptor-based signaling pathways responsible for cancer cell growth, and to uncover mechanisms that result in resistance to targeted therapies.

Our program also aims to identify novel targets for cancer drug development which are suited for antibody-based therapy and visualisation of cancer cells. Through sophisticated protein engineering and molecular imaging techniques, novel diagnostic and therapeutic approaches to a range of cancers are being developed, and extended into clinical studies in cancer patients.

Find out more about the laboratories and groups within the Tumour Targeting Program:

Tumour Targeting Laboratory
Prof Andrew Scott AM
Receptor Biology Laboratory
A/Prof Peter Janes

CENTRE FOR RESEARCH EXCELLENCE IN BRAIN CANCER

The Centre for Research Excellence (CRE) in Brain Cancer was established through $2 Million funding from the Victorian Cancer Agency. Led by Professors Andrew Scott AM and Hui Gan, the CRE is aimed to develop innovative approaches for diagnosing and treating brain cancers, and to take new discoveries into clinical trials in brain cancer patients.

The principal research themes of the CRE in Brain Cancer are:

  1. Developing novel imaging probes: to assist with improved diagnosis and prognostication, better treatment selection and more accurate assessment of
  2. Developing new molecular assays: for better characterisation of brain cancers, leading to improved decision making and selecting the most appropriate treatment for patients.
  3. Developing new drugs and approaches to treatment, which will result in improved responses and survival in brain cancer patients.

This research utilised our access within the ONJCRI, and through collaborations in Australia and internationally, to cutting edge research platforms in genomics, immunology, brain cancer model systems, molecular imaging, and therapeutics development. Our collaborators include the Victorian Comprehensive Cancer Centre (VCCC) brain tumour group, the Cooperative Trials Group For Neuro-Oncology (COGNO), the Australasian Radiopharmaceutical Clinical Trials Network (ARTnet), and the Glioma Longitudinal Analysis (GLASS) Consortium.

In addition to the scientific and clinical aims of the CRE in Brain Cancer, education and training are key components of the overall program.

The Centre is co-led by Prof Andrew Scott AM and Prof Hui Gan

BIOINFORMATICS AND CANCER GENOMICS LABORATORY

The Bioinformatics and Cancer Genomics Laboratory (BCG Laboratory) was established to support the bioinformatics needs at the Olivia Newton-John Cancer Research Institute. The BCG Laboratory is internationally recognised as a leading group in developing state-of-the-art bioinformatics tools for analysing genomics data including next-generation and third-generation sequencing data.

Our Laboratory’s research themes include:

  1. Map and quantify expression data generated from single-cell and bulk RNA sequencing
  2. Discover genomic mutations including structural variants in cancer genomes
  3. Use genomics data to understand the molecular mechanisms underlying development of cancer and immune diseases
  4. Use machine learning algorithm to predict the prognosis and drug response of various types of cancer

Our team collaborates with many laboratories and groups at ONJCRI. We also collaborate with laboratories from other institutes including Doherty Institute, Walter and Eliza Hall Institute, Diamantina Institute and Peter MacCallum Cancer Centre. We also collaborates with clinicians from various hospitals.

Our team also provides bioinformatics consultations and workshop training to students and staff at the ONJCRI.

The BCG Laboratory is led by Prof Wei Shi