Sarah C. Hughes
Ph.D., University of Toronto
Adjunct Associate Professor
Current Research Interests
A genetic model for Neurofibromatosis Type II: Identification and characterization of protein partners of the Merlin tumour suppressor protein
We study the molecular mechanisms that link polarity and proliferation in epithelial cells. When cells lose this linkage they often become metastatic. Specifically, we 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, we are 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. We have already identified several proteins that interact with Merlin, and are currently studying how these control proliferation and adhesion within the cell. We hypothesize that Merlin is functioning as part of a multi-protein complex to control proliferation and polarity. Other proteins include kinases, scaffold proteins and proteins involved in post-transcriptional regulation. The approaches we use include genetic analysis, molecular and cell biology, biochemistry, and advanced microscopy.
Namal Abeysundara, Andrew J. Simmonds, and Sarah C. Hughes. 2017. Moesin is involved in polarity maintenance and cortical remodelling during asymmetric cell division. Mol. Biol. Cell mbc.E17-05-0294; First Published on December 27, 2017;doi:10.1091/mbc.E17-05-0294
Devon R Germain, Lei Li, Matthew R Hildebrandt, Andrew J. Simmonds, Sarah C. Hughes, and Roseline Godbout. (2015). Loss of the Drosophila melanogaster RNA binding protein Ddx1 leads to reduced size and aberrant gametogenesis. Developmental Biology 407(2): 232-45.
Carolina Ortiz Sandoval, Sarah Hughes, Joel Dacks, Thomas Simmen. (2014).Interaction with the effector Dynamin-Related Protein 1 (Drp1) is an ancient function of Rab32 subfamily proteins. Cellular Logistics. 4(4): e986399-7.
Abeysundara N, Leung AC, Primrose DA, Hughes SC. Regulation of cell proliferation and adhesion by means of a novel region of drosophila merlin interacting with Sip1. Dev Dyn. 2014 Dec;243(12):1554-70. Epub 2014 Oct 1.
Li X, Zhuo R, Tiong S, Di Cara F, King-Jones K, Hughes SC, Campbell SD, Wevrick R. The Smc5/Smc6/MAGE complex confers resistance to caffeine and genotoxic stress in Drosophila melanogaster. PLoS One. 2013;(8)3:e59866. Epub 2013 Mar 28.
Yang Yang, David A. Primrose, Albert C. Leung, Ross B. Fitzsimmons, Matt C. McDermand, Alison Missellbrook, Julie Haskins, AnneLiese S. Smylie and Sarah C. Hughes. 2012. The PP1 phosphatase Flapwing regulates the activity of Merlin and Moesin in Drosophila. Developmental Biology. V361 pgs.412-426.
Fred D. Mast*, Jing Li*, Maninder K. Virk, Sarah C. Hughes, Andrew J. Simmonds and Richard A. Rachubinski. 2011. Characterization of the functional requirement for Drosophila Pex1 during embryonic development. Disease Models and Mechanisms. V4 pgs. 659-672.
Hughes, S.C.*, Formstecher, E., and R.G. Fehon. 2010. Sip1, the Drosophila orthologue of EBP50/NHERF1, interacts with the Sterile 20 family kinase Slik to regulate Moesin activity. Journal of Cell Science 123, 1099-1107. * denotes corresponding author
Edan Foley, Harriet Harris, Sarah C. Hughes, and Andrew J. Simmonds. 2009. I CanFly – Can you? - The 10th Canadian Drosophila Research Conference, Jasper/Edmonton, Alberta, Canada. Fly 3:4, 1-2
Deng, H., Hughes S.C., Bell J.B. and Simmonds A.J. (2009). Vestigial, Scalloped and Dmef2 form alternative transcriptional complexes during muscle differentiation in Drosophila melanogaster. Molecular Biology of the Cell, V20:256-269.