Regulation of tumour progression by alternative splicing
Tumour cells initiate many of their progressive properties (e.g. metastasis, angiogenesis, anti-apoptosis), by switching expression of splice isoforms of multipel genes (e.g. anti-angiogenic VEGF to pro-angiogenic VEGF, or pro-apoptotic Caspase to anti-apoptotic Caspase). We are investigating the regulation of this splicing and developing new compounds that can prevent tumour growthg through this strategy.
Cancer genetics and stem cell
The Cancer Genetics and Stem Cell group led by Dr Abdolrahman Shams Nateri try to understand the molecular and cellular nature of the “stem cell niche” under physiological conditions that allows the expression of oncogenes and/or the deletion of tumour suppressor genes (e.g. FBXW7 (hCDC4), β-Catenin/TCF4, NANOG and their molecular partners) in defined cell lineages, including tissue-specific stem cells and tissues in murine models for various human cancers.
It also try to define the possible factors and signalling pathways that reprogram human cancer cells to induced pluripotent cancer (iPC) cells and direct differentiation of human pluripotent stem (iPS) cells into intestinal tissues and hopefully small molecule drugs that selectively target cancer stem cells for differentiation (differentiation therapy).
Paracrine signalling in cancer development/progression
Paracrine signalling between stromal cells and cancer cells influence growth and metastasis of cancer cells. In the liver colon cancer metastasis setting, the role of c-met activation is being investigated. Hepatocyte growth factor (HGF)/scatter factor, upon binding to its receptor, the proto-oncogene c-Met, induces numerous signalling pathways leading to increased mitogenesis, dissociation and motility, morphogenesis, proliferation, and invasion and metastasis of epithelial cells.
Links to epithelial mesenchymal transition and cancer stem cell evolution are also being studied, and the role of paracrine hedgehog signalling in promoting and supporting the stromal population in tumours, in particular in pancreatic cancer, is being investigated. RNAi library screening is being applied to identify novel paracrine signalling pathways activated when epithelial and stromal cells are co-cultured.