Sarah Hughes

Research Areas

Neurofibromatosis Type II, developmental genetics, tumour suppressor proteins, cytoskeleton, cell adhesion, post-transcriptional regulation.

Current Research Interests

A genetic model for Neurofibromatosis Type II: Identification and characterization of protein partners of the Merlin tumour suppressor protein

I study the molecular mechanisms that link polarity and proliferation in epithelial cells. When cells lose this linkage they often become metastatic. Specifically, I use Drosophila melanogaster (the fruit fly) as a genetic model to study Neurofibromatosis Type 2 (NF2), an inherited cancer of the brain and spinal cord. Mutation or loss of the NF2 gene is also associated with metastasis of several non-neuronal tumours. Merlin, the protein product of the NF2 gene, is a tumour suppressor that interacts with the plasma membrane and the cytoskeleton. However, the molecular mechanism of how Merlin acts as a tumour suppressor is not known. To address this question, I am taking the approach of identifying and characterizing proteins that interact with Merlin. Drosophila provides a unique toolbox of powerful genetic techniques to determine the function of Merlin and its interacting proteins. I have already identified several new proteins that interact with Merlin and am currently studying how these control proliferation and adhesion within the cell. The approaches my laboratory will be using range from genetic analysis, molecular and cell biology, biochemistry, and advanced microscopy.

Positions Available

Undergraduate (January 2008) and summer student projects (summer 2008) are available to meet specific student interests. Positions for graduate students starting on or after September 2008 will be available. I am looking for highly motivated, academically excellent students to obtain a M.Sc. or PhD in Medical Genetics.

Hughes, S.C. and R.G. Fehon. Sip-1, the Drosophila homologue of EBP50/NHERF1 functionally interacts with the ERM protein Moesin and is required to maintain epithelial integrity in follicle cells. (in preparation).

Hughes, S.C. and R.G. Fehon. (2007). Understanding ERM Proteins – The awesome power of genetics finally brought to bear. Current Opinion in Cell Biology, 19:51-56.

Hughes, S.C. and R.G. Fehon. (2006). Phosphorylation and activity of the tumor-suppressor Merlin and ERM protein Moesin are coordinately regulated by the Slik kinase. Journal of Cell Biology, 175(2):305-313.

Speck, O., S.C. Hughes, N.K. Noren, R.M. Kulikauskas and R.G. Fehon (2003). Moesin functions antagonistically to the Rho pathway to maintain epithelial integrity. Nature 421:83-87.