Background
Tumour hypoxia is one of the hallmarks of solid tumours. Hypoxia is a powerful trigger of angiogenesis and associated with carcinogenesis, tumour progression and resistance to therapy. Cellular hypoxia triggers a broad response that is primarily mediated by the heterodimeric transcription factor hypoxia inducible factor alpha (HIF-1alpha). Several studies have associated HIF-1 overexpression with human cancer progression. HIF-1 is often overexpressed in colon, breast, gastric, lung, skin, ovarian, pancreatic, prostate and renal carcinomas, and is associated with cell proliferation (Zhong et al., 1999). Immunohistochemical analyses have shown that increased levels of intracellular HIF-1 are associated with breast carcinogenesis (Bos et al., 2001) and poor prognosis in invasive breast cancer (Bos et al.2002) and resistance to therapy in head and neck cancer, ovarian cancer and oesophageal cancer (Talks et al., 2000; Zhong et al., 1999).
Research
1. To unravel the molecular pathways leading to HIF-1alpha activation and stabilization, and unravel HIF-1alpha signaling pathways.
2. Isolation of llama derived single chain antibodies against various functional domains of HIF-1alpha and other hypoxia related proteins for therapeutic targeting and imaging.
3. Translational research on the diagnostic, prognostic and predictive value of HIF-1alpha and other hypoxia related proteins in breast, endometrial and brain cancers.