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Our lab studies apoptosis (the main form of programmed cell death) and it's effectors, mitochondria and caspases. Beside having an important role in development, apoptosis is often affected in several pathologies: in cancer, apoptosis is most of the time blocked allowing rapid tumour growth, while in neurodegenerative diseases there is an excess of apoptosis.
The key player in apoptosis is the mitochondria, an organelle that on one side provides the energy needed for survival while it also holds the power to kill the same cell: this happens when the mitochondria permeabilise following a lethal stress and triggers caspase activation. Caspases are proteases that efficiently kill the cell within minutes.
Our team is interested in non-canonical roles that mitochondria and caspases have in tumourigenesis and development. Since it was recently showed that only few mitochondria can permeabilise allowing non-lethal caspase activation, we currently investigate the role of this discrete caspase activation in various settings ranging from cancer cell migration and invasion to stemness or senescence.
Links:
Research articles
- K. Berthenet, C. Castillo Ferrer, N. Popgeorgiev, H. Hernandez-Vargas, G. Ichim (2019) Failed apoptosis enhances melanoma cancer cells aggressiveness. bioRxiv 755744; doi: https://doi.org/10.1101/755744
- Roumane, A., El Fassi, C., Ichim, G. (2018) Caspase-independent cell death does not elicit a proliferative response in melanoma cancer cells. BMC Cell Biology, 19:11
- Correia-Melo, C.*, Ichim, G.*, Tait, S. W. and Passos, J. F. (2016) Depletion of mitochondria in mammalian cells through enforced mitophagy. Nature Protocols.
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Ichim, G., Lopez, J., Ahmed, S.U., Muthalagu, N., Giampazolias, E., Delgado, M.E., Haller, M., Riley, J.S., Mason, S.M., Athineos, D., Parsons, M. J.,van de Kooij, B., Bouchier-Hayes, L., Chalmers, A. J., Rooswinkel, R. W., Oberst, A., Blyth, K., Rehm, M., Murphy, D. J., Tait, S. W. (2015). Limited mitochondrial permeabilization causes DNA damage and genomic instability in the absence of cell death. Molecular Cell 57, 860-872.
Reviews and book chapters
- Keller, N., Ozmadenci, D., Ichim, G., Stupack, D. (2018) Caspase-8 function, and phosphorylation, in cell migration. Semin Cell Dev Biol.Feb 16. pii: S1084-9521(17)30529-3.
- Ichim, G., Tait S.W. (2016) A fate worse than death: apoptosis as an oncogenic process. Nature Reviews Cancer 16: 539-48
- Oberst, A., Ichim, G., Tait, S.W. (2016) Mitochondrial permeabilization: From lethality to vitality. Mitochondria and cell death. Book series: Cell Death in Biology and Diseases Pages: 213-226 (2016)
- Ichim, G., Tait, S.W. (2015). Necroptosis: Fifty shades of RIPKs. Molecular and Cellular Oncology 2,2.
- Tait, S.W., Ichim, G., and Green, D.R. (2014). Die another way--non-apoptotic mechanisms of cell death. Journal of Cell Science 127, 2135-2144.
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