Cell Biology: Ferguson Lab
Extensive Research Description
Specific projects under development include:
1. Understanding signaling mechanisms that coordinate lysosomal function (macromolecule degradation) with lysosomal biogenesis. How does a cell match lysosomal capacity with demand? How are signals transduced from the interior of the lysosome to the cytoplasm?
2. Investigation of the cellular function of genes underlying neuronal ceroid lipofuscinosis. Mutations in multiple human genes have been identified as causes of this lethal childhood neurodegenerative disease arising from lysosomal dysfunction. However, the basic cellular functions of the normal proteins that they encode remain largely unclear. I aim to take advantage of the clues gained from human genetic studies to guide efforts to achieve better cell biological understanding of these diseases and of the normal regulation of lysosomal function that becomes impaired in these disease states.
3. Investigation of the mechanisms that cause neuronal lysosome trafficking defects in Alzheimer’s disease.
- Ferguson, S.M. 2015. Beyond indigestion: emerging roles for lysosome-based signaling in human disease. Curr Opin Cell Biol. 35:59-68.
- Petit, C.S., Roczniak-Ferguson, A., Ferguson, S.M. Recruitment of folliculin to lysosomes supports the amino acid-dependent activation of Rag GTPases. J Cell Biol., 30;202(7):1107-112, 2013. PMID: 24081491.
- Roczniak-Ferguson, A., Petit, C.S., Qian, S., Ky, J., Angarola, B., Froehlich, F., Walther, T.C., Ferguson, S.M. The Transcription Factor TFEB links mTORC1 Signaling to Transcriptional Control of Lysosome Homeostasis. Science Signaling, Jun 12;5(228): ra42, 2012.
- Ferguson, S.M. & De Camilli, P. Dynamin, a membrane-remodelling GTPase. Nature Reviews. Molecular Cell Biology (13(2), 75-88, 2012.
- Overlapping role of dynamin isoforms in synaptic vesicle endocytosis. Raimondi A1, Ferguson SM, Lou X, Armbruster M, Paradise S, Giovedi S, Messa M, Kono N, Takasaki J, Cappello V, O'Toole E, Ryan TA, De Camilli P. (2011) Overlapping role of dynamin isoforms in synaptic vesicle endocytosis.
- Coordinated actions of actin and BAR proteins upstream of dynamin at endocytic clathrin-coated pits. Ferguson, S.M., Raimondi, A, Paradise, S., Shen, H., Mesaki, K., Destaing, O. Ko, G., Takasaki, J., Cremona, O., O’Toole, E., De Camilli, P. (2009) Coordinated actions of actin and BAR proteins upstream of dynamin at endocytic clathrin-coated pits.
- Ferguson S.M., Brasnjo G, Hayashi M, Wolfel M, Collesi C, Giovedi S, Raimondi A, Gong LW, Ariel P, Paradise S, O'Toole E, Flavell R, Cremona O, Miesenbock G, Ryan TA, De Camilli P. A selective activity-dependent requirement for dynamin 1 in synaptic vesicle endocytosis. Science, 316(5824):570-74, 2007