About me
Understanding the intrinsic mechanisms behind how cancerous cells grow and thrive can help answer one of science’s toughest questions: how can we cure cancer? Having completed my BSc in Biomedical Science and MSc in Translational Neuroscience, both in Sheffield, I knew I wanted to stay and continue utilizing zebrafish as a model for human disease. I can contribute to an exciting field, which has recently been recognised in the media due to the Nobel prize, and further our understanding of what makes cancer such a difficult disease to treat.
My project
Radiotherapy and chemotherapy are ineffective against renal cell carcinoma (RCC). This cancer is caused by mutations in the von Hippel-Lindau protein (VHL), which helps to maintain hypoxia-inducible factor (HIF) at low levels during normal oxygen levels. However, when VHL is mutated, HIF is constantly activated in both normoxia and hypoxia – stimulating genes downstream that promote cell survival, such as angiogenesis and cellular proliferation. High levels of HIF in RCC patients seems to protect them from traditional anti-cancer treatments. Therefore, I shall be identifying methods to downregulate HIF, allowing for cells to be resensitised to radiotherapy and/or chemotherapy.
One potential target is the glucocorticoid/mineralocorticoid (GC/MC) pathway, which is activated during hypoxia – upregulating HIF in response. We have identified compounds that inhibit the GC/MC pathway, with the intention of downregulating HIF. Zebrafish models and human RCC cells will be used to establish whether resensitisation is successful. Overall, I hope to contribute to the wider understanding of how high levels of HIF protect the genome from destruction, and identifying compounds that can be used for clinical trials.
Connect
Twitter: @samehkelbadry