Dr Julien Licchesi
Ubiquitin is a versatile post-translational modification which regulates most, if not all, cellular processes including transcription, DNA repair and the cell cycle. This highly conserved protein is best known for its role in mediating protein degradation as part of the ubiquitin-proteasome system. However ubiquitin also has non-degradative functions including in protein trafficking and protein complex formation. Protein ubiquitylation is achieved through a cascade of enzymatic reactions involving an E1-activating enzyme, E2-conjugating enzymes and E3 ubiquitin ligases and which culminates in the covalent attachment of one or more ubiquitin molecules (i.e. ubiquitin chains) onto lysine residue(s) of a protein target. The assembly of ubiquitin into chains requires the formation of an isopeptide bond between any of the seven lysines (K6, K11, K27, K29, K33, K48 and K63) or the N-terminus (i.e. linear ubiquitin) of an acceptor ubiquitin and the C-terminus of a donor ubiquitin. Therefore as many as eight linkage types can be used to assemble homotypic, heterotypic or even branched ubiquitin chains onto protein targets. These linkage-specific ubiquitin chains have different structural and biochemical properties, are regulated by dedicated E3 ubiquitin ligases and deubiquitylases, and modulate specific cell signalling events.
To characterise the biochemical properties and cellular functions of members of the HECT family of E3 ligases and the OTU family of deubiquitylases in normal and disease states, including cancer and neurodegenerative diseases.
- Lecturer in Cellular Biochemistry, University of Bath (from June 2013)
- Postdoctoral Fellow MRC-Laboratory of Molecular Biology, Cambridge, UK (2007-2013)
- Postdoctoral Fellow Johns Hopkins University, Baltimore, USA (2003-2007)
- PhD Cranfield University, UK (1999-2003)
Yu, Y., Yan, W., Liu, X., Jia, Y., Cao, B., Yu, Y., Lv, Y., Brock, M. V., Herman, J. G., Licchesi, J., Yang, Y. and Guo, M., 2014. DACT2 is frequently methylated in human gastric cancer and methylation of DACT2 activated Wnt signaling. American Journal of Cancer Research, 4 (6), pp. 710-724.
Wrangle, J., Machida, E. O., Danilova, L., Hulbert, A., Franco, N., Zhang, W., Glöckner, S. C., Tessema, M., Van Neste, L., Easwaran, H., Schuebel, K. E., Licchesi, J., Hooker, C. M., Ahuja, N., Amano, J., Belinsky, S. A., Baylin, S. B., Herman, J. G. and Brock, M. V., 2014. Functional identification of cancer-specific methylation of CDO1, HOXA9, and TAC1 for the diagnosis of lung cancer. Clinical Cancer Research, 20 (7), pp. 1856-1864.
Zhang, X., Yang, Y., Liu, X., Herman, J. G., Brock, M. V., Licchesi, J. D. F., Yue, W., Pei, X. and Guo, M., 2013. Epigenetic regulation of the Wnt signaling inhibitor DACT2 in human hepatocellular carcinoma. Epigenetics, 8 (4), pp. 373-382.
Licchesi, J. D. F., Mieszczanek, J., Mevissen, T. E. T., Rutherford, T. J., Akutsu, M., Virdee, S., El Oualid, F., Chin, J. W., Ovaa, H., Bienz, M. and Komander, D., 2012. An ankyrin-repeat ubiquitin-binding domain determines TRABID's specificity for atypical ubiquitin chains. Nature Structural and Molecular Biology, 19 (1), pp. 62-71.
Licchesi, J. D. F., Van Neste, L., Tiwari, V. K., Cope, L., Lin, X., Baylin, S. B. and Herman, J. G., 2010. Transcriptional regulation of Wnt inhibitory factor-1 by Miz-1/c-Myc. Oncogene, 29 (44), pp. 5923-5934.
Komander, D., Reyes-Turcu, F., Licchesi, J. D. F., Odenwaelder, P., Wilkinson, K. D. and Barford, D., 2009. Molecular discrimination of structurally equivalent Lys 63-linked and linear polyubiquitin chains. EMBO Reports, 10 (5), pp. 466-473.
Tiwari, V. K., McGarvey, K. M., Licchesi, J. D. F., Ohm, J. E., Herman, J. G., Schübeler, D. and Baylin, S. B., 2008. PcG proteins, DNA methylation, and gene repression by chromatin looping. PLoS Biology, 6 (12), pp. 2911-2927.
Licchesi, J. D. F., Westra, W. H., Hooker, C. M. and Herman, J. G., 2008. Promoter hypermethylation of hallmark cancer genes in atypical adenomatous hyperplasia of the lung. Clinical Cancer Research, 14 (9), pp. 2570-2578.
Licchesi, J. D. F., Westra, W. H., Hooker, C. M., Machida, E. O., Baylin, S. B. and Herman, J. G., 2008. Epigenetic alteration of Wnt pathway antagonists in progressive glandular neoplasia of the lung. Carcinogenesis, 29 (5), pp. 895-904.