Future Seminar Dates

Title:   A zebrafish model to characterise von Hippel-Lindau disease and hypoxic signalling.

Speaker:   Dr Freek van Eeden, Department of Biomedical Science.

Time:   12:45pm - 1:45pm

Venue:   Lecture Theatre 3, F Floor Medical School.

Abstract:   Von Hippel-Lindau (VHL) disease is a heritable disorder leading to benign and malignant tumours in different organ systems. Patients often develop renal cysts and the malignant degeneration of these renal cysts to clear cell renal cell carcinoma (ccRCC) is the leading cause of death. VHL protein has been attributed to have tumour suppressor function and is also known to play a key role in the oxygen-sensing pathway leading to the degradation of hypoxia-inducible factor-a (HIF-a). Zebrafish has 2 VHL homologues, vhl with 51% identity to human VHL and vll with 35% identity to the human gene. We have identified a loss of function mutation in vhl, we have shown that these mutants show a strong hypoxic response in a normoxic environment, including hyperangiogenic phenotype that we are currently characterising.

In addition, mutant embryos also exhibit late onset kidney tubule defects with abnormal cellular morphology. We have generated a Tg(PHD3:GFP) transgenic line, which exhibit robust GFP expression in the vhl mutant background, essentially acting as an in vivo reporter for hypoxia, and are exploiting this line to study the hypoxic signalling pathway and assay the tumour suppressor function of VHL in fish.