Angiogenesis is the development of new blood vessels from an existing vascular bed. Normal vascular proliferation only occurs during embryonic development, the female reproductive cycle and wound healing. However, many pathological conditions are characterised by persistent, unregulated angiogenesis. Excessive angiogenesis leads to cancer, endometriosis and atherosclerosis, while inadequate angiogenesis is responsible for chronic wounds, stroke and alopecia.
Over the past few years, we have been focusing on the mechanisms of action of two angiogenic factors: thymidine phosphorylase (TP) and hepatocyte growth factor/scatter factor (HGF/SF) [1-4]. In collaboration with colleagues at Babraham Institute, MRC Group Factor Group and Massachusetts Institute of Technology, we have added significant knowledge in the signalling mechanisms of HGF/SF. With Reproductive Molecular Research Group at Cambridge, we demonstrated that antiangiogenic agents are effective inhibitors of endometriosis .
During this time, we have also successfully strengthened our resources to build a platform to investigate the angiogenesis-modulating effects of pure compounds from traditional Chinese medicine (TCM) and other natural products. In particular we aim to identify the actives from plant extracts, test their activities and elucidate their mechanisms of action at the cellular and molecular levels. Supported by successive grants from the Hong Kong University Grants Committee, our collaboration with Hong Kong Baptist University has shown several actives from herbs to modify proliferation, tube formation and gene expression of human endothelial cells, and angiogenesis in vivo . In a joint venture with NuLiv Science (Taipei), we are now spearheading research into discovering angiogenesis modulators from TCM. Using the cDNA microarray developed by Dr Cristin Print and colleagues of Department of Pathology, we are evaluating the effects of plant actives on apoptosis of vascular and non-vascular cells. Dr Kathryn Lilley of Department of Biochemistry shares her expertise in proteomics to help us elucidate the actions of these actives.
A new project with Professor Steve Ley of Department of Chemistry led to the discovery of a series of inhibitors of histone deacetylase, an enzyme implicated in angiogenesis . Working closely with Dr Rik van Veen of this Department, we also aim to discover herbal actives for the reversal of multi-drug resistance. Expertise is being developed in the areas of stem cells, hair follicles and keratinocytes. Taken together, these new aspects of angiogenesis research are providing important clues for the development of new drugs for the prevention and treatment of angiogenic diseases.