Dr Nikolas Haass, Head & Cameron Research Fellow
Melanoma is the most aggressive and deadly form of skin cancer, and has a particularly high incidence in Australia. There is an urgent need to find new therapies to improve the dismal prognosis of metastatic melanoma. Although early stage melanoma can be successfully treated through surgery, there is no cure once it has spread and become metastatic. Fewer than 10 per cent of metastatic melanomas respond to dacarbazine, currently the only standard drug. Modern targeted therapy appears to be more promising, but we still have not cured melanoma.
The resistance of metastatic melanoma to conventional chemotherapy may be explained by the existence a multi-drug resistant population of cells, so-called melanoma initiating cells or melanoma stem cells (MSC). The hypothesis is that melanomas recur because all tumour cells except the MSC have been killed, and the MSC then initiate the regrowth of the tumour.
Dr Nikolas Haass’s research focuses on experimental melanoma therapy. His interests are the understanding of (1) interactions of melanoma with its microenvironment, (2) signalling pathways in melanoma, and (3) the characterisation of MSC.
In collaboration with Dr Smalley and Professor Herlyn from the Wistar Institute in Philadelphia, Dr Haass has developed a novel cell culture model where melanoma cells, grown as 3D spheroids, are implanted into collagen gels to mimic the ‘tumour organ’, ie tumour architecture and microenvironment. An example of experiments on the 3D melanoma spheroids is given in the figure.
To take his results on the 3D melanoma model from theory to practice, Dr Haass also investigates melanoma in mice, using the cutting-edge intravital multi-photon microscopy established by Professor Wolfgang Weninger’s group. This set-up allows the visualisation of the behaviour of melanoma cells and their response to treatment in real-time in vivo. Dr Haass’s team uses these models to gain new insights into melanoma biology, particularly with regard to identifying novel melanoma therapies.
The research team
- Andrea Anfosso, Research assistant
- Nethia Mohana-Kumaran, PhD student
- Paula Nascimento, Master’s student
- Garth Douglas, Research assistant (to March 2009)
- Jana Knuever, Visiting scientist
Multiple signalling pathways must be targeted to overcome drug resistance metastatic melanoma cells. Model: 3D melanoma spheroids. (A) wild-type, untreated; (B) PI3K knock-down, untreated; (C) wild-type, treated with a MAPK pathway inhibitor; (D) PI3K knock-down, treated with a MAPK pathway inhibitor. Green: live cells; red: dead cells. Note the slight effect of inhibition of each pathway on invasion and survival (B, C), but synergy of the inhibition of both PI3K and MAPK pathway (D).