Group leader
Research focus
Traditional chemotherapy agents attack the cancer cells. Some of the newer anti-cancer agents
that are being developed target instead, the normal cells of the tumour
stroma.
The concept of targeting the stroma to kill the cancer has arisen from the accumulating
evidence that the stroma plays an essential role in supporting the growth of solid
cancers. The tumour stroma comprises of multiple cell types and includes the endothelial cells, immune T- and B-lymphocytes, natural killer cells, dendritic cells, fibroblasts,
neutrophils and macrophages. Many of these cells have been actively recruited into
the tumour in response to factors released by the cancer cells. Once in the tumour
site, these non-cancerous cells are exploited by the cancer cells to perform functions
that promote tumour growth and survival.
Our research programme is focused on dissecting the molecular interactions between
the cancer cells and the stromal cells, and in the development of agents that can
disrupt these interactions to provide therapeutic gain.
Current research interests
- The signalling pathway(s) and molecular target(s) of DMXAA, a vascular disrupting
agent in Phase III trials
- The development of analogues of an anti-angiogenic and non-teratogenic metabolite
of thalidomide for the treatment of multiple myeloma
- Development
of novel inhibitors of indoleamine 2,3-dioxygenase for reversal of tumour
mediated immune suppression as adjunct therapy for cancer
- Dissecting the stromal cell-cancer cell interactions in malignant melanoma
- Exploring the efficacy of stromal targeting agents for the treatment of primary
and metastatic brain cancers
Technologies and methodologies utilised
• Luminex 100
TM for simultaneous detection of multiple analytes, cytokines, proteins
• Calliper IVIS imaging for detection of intra-cranial tumours and metastases
• Single- and triple-quadrupole-mass spectrometry for detection of therapeutic drugs
and their metabolites in biological fluids
• Micro-dialysis sampling of intracellular fluid of living tissues in real-time
• Multi-colour immuno-fluorescence labelling of tumour cryosections for analysis
stromal infiltrates
• FACS analysis for fine dissection of stromal cell numbers in tumours before and
after treatment
• Proteomic profiling using ion-trap mass spectrometry coupled to Mascot search
engine and SwissProt database for analysis of drug action on cells
• Full tissue culture facilities for growth of human and murine tumour cells and
primary immune cells
• Molecular biology, including Westerns, EMSAs, RT-PCR, micro-arrays, siRNA knock-downs,
cell transfections
Group members
