Molecular Horizons' basic cancer research and drug development grouping works on understanding the biological processes underlying cancer progression and develops methods for cancer prevention, detection and treatment. They use a range of cell and molecular biology techniques, medicinal chemistry and preclinical animal models to meet the demand for novel anti-cancer drug testing and research leading to a range of innovative cancer treatment options.
Our research efforts focus on developing and applying theoretical and computational tools to understand the structure-dynamics-function relationship in the complex (bio)molecular and nanoscale systems. Complementary to experimental investigations, such studies can gain new insights at the atomic level into the underlying mechanism and provide necessary knowledge for molecular engineering and discovery of novel therapeutics. Current research projects include computational studies of protein-ligand interactions, mechanistic studies of enzymatic reactions, and computer-aided enzyme design.
View Associate Professor Haibo Yu’s Scholar page
Please contact hyu@uow.edu.au for more information.
The Hyland research group develops new catalytic chemical reactions for the synthesis of biologically important molecular motifs. In particular, we focus on the stereoselective synthesis of complex heterocycles via transition metal catalysis. The ultimate aim of our work is to develop tools for chemists and biologists to build complex molecules that may be used in new pharmaceuticals, biological probes or materials, while contributing to fundamental chemical knowledge. We also use our knowledge of reaction mechanisms and organometallics to design selective anti-cancer pro-drugs that are activated by reactive oxygen species.
View Dr Chris Hyland's Scholars page
Contact chrhyl@uow.edu.au for more information.
A key focus of the lab is to better understand the biological processes that contribute to the invasion and spread of cancer around the body, a process known as metastasis, which is the leading cause of cancer-related deaths. We have made significant progress towards identifying the role of a tissue-degrading system integral to cancer metastasis with multiple publications. We know that high levels of a key component of this system, the enzyme uPA, results in patients with many types of cancer having a greater chance of developing metastasis. As a cell surface protein, uPA represents an accessible druggable target for stopping the metastatic process. To this end, we are utilising a naturally occurring inhibitor of uPA called PAI-2 (Figure 1). Another project is repurposing the old drug amiloride into a potent dual-targeting inhibitor of two well-established cancer biomarkers including uPA.
Our lab also utilises patient tumours for mutational and expression analyses of biomarkers of metastasis and actionable therapeutic targets in skin cancer (Figure 2). Patient-derived cultures and xenografts have been established from fresh tumours and isolated CTCs, as models for targeted genetic manipulation and drug responsiveness studies.
The Ranson lab also contributes to on-going collaborations investigating the role of the uPA system in protein misfolding diseases such as pregnancy preeclampsia and in streptococcal pathogenesis.
View Senior Professor Marie Ranson’s Scholars page
Contact mranson@uow.edu.au for more information.
The Immunology and Cell Signalling Group focuses on extracellular signalling pathways between immune cells in the context of health and disease in humans and companion animals. A key focus of the group is the study of signalling pathways mediated by extracellular ATP and purinergic receptors (mainly P2X7, P2X4, P2Y12 and A2A), as well ecto-enzymes (mainly CD39 and CD73), which regulate the availability of extracellular nucleotides and nucleosides (see Figure). These pathways are currently being investigated in the context of immunity, inflammation and blood clotting, as well as diseases such as cancer, graft-versus-host disease, psoriasis, inflammatory pain and motor neuron disease.
To better understand the above, the group utilises a number of technologies and approaches including flow cytometry, mass cytometry, cation flux assays, recombinant DNA techniques, mouse models including humanised mice, and blood samples from people, cats and dogs.
Purinergic signaling pathways amongst immune cells. ATP released from damage, infected or malignant cells can activate P2X7 (and P2X4, not shown) on leukocytes to promote inflammation and immunity. Extracellular ATP can be sequentially degraded by the ecto-enzymes CD39 and CD73 to adenosine, which can activate A2A on leukocytes to suppress inflammation and immunity. ADP released from cells or resulting from ATP degradation can activate P2Y12 on platelets to promote coagulation.
View Associate Professor Ronald Sluyters Scholar page
Contact rsluyter@uow.edu.au for more information.
Our lab investigates therapeutic strategies to prevent the development of graft-versus-host disease. Donor stem cell transplantation can be a curative therapy for people with blood cancer. However, in 50% of recipients receiving a donor stem cell transplant, the immune cells in the transplant (graft) attack the patient (host) leading to graft-versus-host disease. The donor immune cells are activated damaging the liver, gut and skin and other organs in the recipient and this leads to a debilitating and painful disease with a 15% mortality rate. Current therapies are limited, using broad range immunosuppression, which leads to cancer relapse and infection.
In our research laboratory, we use strategies that specifically deplete the donor immune cells that attack the organs to prevent graft-versus-disease, while retaining the immune cells that respond to cancer and infection. Further, we target the purine signalling pathway, including the P2X7 receptor, known to play a role in graft-versus-host disease development, and we examine combined therapies to prevent disease in preclinical models.
View Dr Debbie Watson’s Scholars page
Contact dwatson@uow.edu.au for more information.