Brief career history

• 2006- present: Senior Lecturer, University of Sheffield
• 1999 - 2005: Junior Group Leader Hubrecht Laboratory, Utrecht, The Netherlands
• 1997 - 1999: Post-doctoral worker, D. StJohnston Lab, Wellcome/CRC Inst. Cambridge UK
• 1992 - 1997: PhD, C. Nüsslein-Volhard Lab. Max Planck Inst. für Entwicklungsbiologie, Tübingen, Germany
• 1986 - 1992 MSc. Wageningen Agricultural University, The Netherlands

Research interests

Using the zebrafish as a genetic tool to study development and disease. We are interested in understanding the role of the patched genes in Hedgehog signaling. In addition, we have created a knockout for the von Hippel Lindau disease (VHL) gene and are interested in modeling VHL deficient cancers in zebrafish.

Professional activities

• Invited teacher at regular EMBO courses at the MPI in Tübingen (recently also Sheffield)
• Presenter at open science days and public lectures in Utrecht/Wageningen
• International collaboration on TILLING with Hubrecht Laboratory Utrecht/Sanger Inst. Cambridge
• Invited speaker at: ZDM8, Boston,  Aug 2015; Zebrafish PI Meeting Ein gedi 2014; BSDB meeting 2013; European zebrafish meeting Barcelona 2013
• Reviewer for: BBSRC, Development, FNRS, Swiss research council, Singapore, Hong-Kong and many others

Full publications

Disease modelling in zebrafish

Understanding VHL and hypoxic signalling in Cancer

The zebrafish provides a powerful organism to model human development and disease.  We are exploiting and developing the zebrafish, e.g. by creating such disease models, by using knockout technology like CRISPR, or by looking for chemicals that can modify disease-relevant phenotypes.

One of our current projects, models the human Von Hippel Lindau disease,  caused  by mutation of the VHL gene. VHL is a negative regulator of the Hypoxia Inducible Factor (HIF) signalling pathway, which is vital for development and survival of many tumours. However, this is not the only function of VHL and over the years numerous others have been identified. We found that in zebrafish, the functions of human VHL have been split over two genes, which we named vhl and vhl-like (vll).

Interestingly, we found that the fish vhl gene has an important role in HIF regulation, as mutants we made by reverse genetics show all hallmarks of an inappropriate hypoxic response under normoxic conditions. The role of vll was initially enigmatic, null mutants that we created in this gene were viable and fertile. However, using a unique and novel in vivo reporter for genome stability that we created, we discovered that the vll gene is important for maintaining genome stability, which is a major driver for tumour initiation. This is what we are currently trying to understand better.

Current collaborations: Sherif El-Khamisy (genome stability), Albert Ong (pkd2 model), Jane McKeating (Birmingham), Francesco Argenton (Padua) (both glucocorticoid-HIF interaction).

Undergraduate and postgraduate taught modules

Level 1:

• BMS109 Laboratory Skills in BMS

Level 2:

• BMS237 Advanced Developmental Biology

Level 3:

• BMS339 Patients as Educators Project
• BMS369 Wet Lab Project (Co-ordinator)