Overview of interests
Dr. Ferguson’s research is focused on the functional regulation and activity of G protein-coupled receptors (GPCRs) as a consequence of their interactions with other proteins expressed inside and outside of the cell and how these interactions regulate both normal pathological cell signaling. His current research efforts are primarily focused on the role of metabotropic glutamate receptor signaling in Huntington’s, Alzheimer’s and Parkinson’s disease, the regulation of serotonin receptor activity by corticotrophin releasing factor receptors in response stress with a goal of understanding the effect stress has on anxiety and depression behaviours, as well as understanding the molecular changes in GPCR signaling associated with hypertension.
Dr. Ferguson was the first to identify b-arrestins as endocytic adaptor proteins for GPCRs and to show that they contribute to the coupling of GPCRs to G protein-independent signal transduction pathways. His laboratory has extensively studied the mechanisms by which the internalization, intracellular trafficking and recycling alter GPCR activity and the consequence of these processes to physiological cell signaling. He has identified novel mechanisms contributing to disease processes involved in hypertension, anxiety, stress and depression as well as neurodegenerative diseases such as Alzheimer’s and Huntington’s diseases. He is investigating the role of PDZ proteins in contributing to maladaptive GPCR signaling receptors in stress, anxiety and depression and is developing small molecule inhibitors of these interactions as potential drug candidates. His lab is also currently investigating the utility of repurposing exist receptor antagonists for the treatment of neurodegenerative disease.
- K. S. Abd-Elrahman, A. Hamilton, S. R. Hutchinson, F. Liu, R. C. Russell, S. S. G. Ferguson, mGluR5 antagonism increases autophagy and prevents disease progression in the zQ175 mouse model of Huntington’s disease. Sci. Signal. 10, eaan6387 (2017). Issue date is December 19th , 2017. .
- Hamilton, A., Vasefi, M., Vander Tuin, C., McQuaid, R. J., Anisman, H. and Ferguson. S. S. G. (2016) Chronic pharmacological mGluR5 inhibition ameliorates cognitive impairment and pathogenesis in an Alzheimer’s disease mouse model. Cell Reports 15, 1-7
- Dunn, H. A., Yuan, G. Y., Chahal, H. S., Holmes, K., Parikh, R., Caetano, F. A. and Ferguson, S. S. G. (2016) PSD-95 regulates corticotropin-release factor receptor 1 trafficking and -arrestin2 recruitment. Cell. Signal.28, 531-540.
- Dunn, H. A. and Ferguson, S. S. G. (2015) PDZ proteins: Role in G protein-coupled receptor trafficking, maturation and endocytosis. Mol. Pharmacol.88, 624-639.
- Tutunea-Fatan, E., Caetano, F. A., Gros, R., and Ferguson, S. S. G. (2015) GRK2 targeted knock-down results in spontaneous hypertension and altered vascular GPCR signaling. J. Biol. Chem.290, 5141-5155.
- Hamilton, A., Esseltine, J. L., DeVries, R. A., Cregan, S. P., and Ferguson, S. S. G. (2014) Metabotropic glutamate receptor 5 knockout reduces cognitive impairment and pathogenesis in a mouse model of Alzheimer's disease. Mol. Brain7, 40.
- Ribeiro, F. M., DeVries, R. A., Hamilton, A., Guimaraes, I. M., Cregan, S. P., Pires, R. G. W., and Ferguson, S. S. G. (2014) Metabotropic glutamate receptor 5 knockout promotes motor and biochemical alterations in a mouse model of Huntington’s disease. Hum. Mol. Genet.23, 2030-2042.
- Dunn, H. A., Walther, C., Godin, C. M., Hall, R. A., and Ferguson, S. S. G.(2013) Role of SAP97 in the regulation of corticotropin-releasing factor receptor 1 endocytosis and ERK1/2 signaling J. Biol. Chem.288, 15023-15034.
- Esseltine, J. L., Ribeiro, F. M., and Ferguson, S. S. G. (2012) Rab8 modulates metabotropic glutamate receptor subtype 1 intracellular trafficking and signaling in a PKC-dependent manner. J. Neurosci.32,16933-16942.
- Magalhaes, A., Holmes, K., Dale, L. B., Drysdale, L., Comps-Agrar, L., Lee, D. K, Yadav, P. N., Poulter M. O., Roth, B. L., Pin, J.-P., Anisman, H. and Ferguson S. S. G. (2010) CRF receptor1 regulatesanxiety behaviour via sensitization of 5-HT2 receptor signaling. Nat. Neurosci.13, 622-629.
- Ribeiro, F. M., Paquet, M., Ferieira, L. T., Cregan, T., Cregan, S. P., and Ferguson S. S. G. (2010) Metabotropic glutamate receptor 1/5 mediated cell signaling pathways are altered in a mouse model of Huntington’s disease. J. Neurosci.30, 316-324.