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

  • 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