Cancer Therapeutics Development Group
Our research focus
Our main research areas are metastatic gastrointestinal and breast cancers. We focus on how inflammation drives the progression to advanced disease and how new treatments could be designed to block its harmful effects.
Understanding how pro-inflammatory pathways drive tumour progression
Inflammatory cytokines make cancer cells more prone to growth and spreading to other parts of the body. By understanding how pro-inflammatory cytokines cause these cellular effects, we have been able to identify molecular targets, for which we are now developing targeted treatments.
Cancer drug discovery
Our research has led to the identification of particular inflammatory pathways, which we now aim to target so we can develop specific treatments which will block cancer growth in the gastrointestinal tract. Working with structural biologists and chemists, we have identified new compounds which we are testing for their ability to block tumour cell survival and spread to other sites in the body. These can then be used in clinical research to provide new treatment options for patients.
Repurposing of commonly used drugs as new cancer treatments
New drug development is a lengthy and resource-intensive process. It makes sense to reassess existing drugs for additional uses at the same time as researching new drug development. We are investigating the therapeutic value of a drug, already clinically approved to treat osteoporosis, as a novel treatment in gastric and colon cancers.
Interaction between the intestinal barrier and the microbiome
We are studying the effects of inflammatory disruption on the intestinal barrier in host-microbiome interaction and how this may contribute to the development of colon cancer. Our team is also exploring the mechanisms of the gut microbiota so that its metabolites may be reinstated following chemotherapy and immunotherapy treatment in cancer patients.
Fast facts
When newly-developed novel compounds are first tested for anti-cancer capabilities using a range of biochemical and cell-based assays.
The body’s natural response to tissue damage, infection and disease.
Different cell types of the body produce pro-inflammatory cytokines as a way of causing inflammation to repair tissue and fight infection.
All the trillions of microorganisms and their genetic material present in the intestinal tract. Mainly comprising bacteria, they play a key role in functions critical to our health.
Recent publications
EMBO Molecular Medicine
Repurposing the selective estrogen receptor modulator bazedoxifene to suppress gastrointestinal cancer growth.
DOI: 10.15252/emmm.201809539
Seminars in Cancer Biology
Repurposing of drugs as STAT3 inhibitors for cancer therapy.
DOI: 10.1016/j.semcancer.2019.09.022
Pharmacology & Therapeutics
Evaluating the benefits of renin-angiotensin system inhibitors as cancer treatments.
DOI: 10.1016/j.pharmthera.2020.107527
Our team
Meet our researchers
- Dr Ashwini Chand - Group Head Publications
- Sarah Bennett (nee To) - Postdoctoral Research Fellow Publications
- Rhynelle Dmello - PhD Student Publications
- Belinda Duscio - Research Assistant Publications
- Pathum Thilakasiri - Research Assistant Publications
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.
Our team
Meet our researchers
- Dr Michael Buchert - Group Head Publications
- Shoukat Afshar-Sterle - Research Assistant Publications
- Annalisa Carli - PhD Student
- Ryan O'Keefe - PhD Student
- Janson Tse - Postdoctoral Research Fellow Publications