Profiles
Prof Chris Hutchison
Contact Prof Chris Hutchison (email at c.j.hutchison@durham.ac.uk)
Biography
Research in my group focuses on the structure, function and biosynthesis of the nuclear envelope. The nuclear envelope is a complex and dynamic structure consisting of a double unit membrane perforated by nuclear pore proteins and supported by a fibrous lamina. The nuclear envelope has been proposed to be an architectural device similar to a geodesic dome, which is designed to resist forces of deformation. The nuclear envelope also breaks down and is reassembled every time a cell divides. This raises questions as to how the assemble and disassembly of the nuclear envelope is regulated. Finally, the nuclear envelope has structural and epigenetic functions. It not only protects chromatin from forces generated by the cytoskeleton but it also controls gene expression by limiting communication across the nuclear membrane but also because nuclear envelope proteins regulate the activity of important transcription co-activators. The function of nuclear envelope has recently been highlighted by the discovery that a number of genetic diseases, including progeria, bone diseases, muscular dystrophy, cardiomyopathy and white fat disorders, arise through mutations in nuclear envelope proteins.
Our group uses a wide range of in vitro technologies to understand how these proteins function and therefore how to understand human pathologies. This includes a wide range of cell culture models, cell free nuclear assembly systems, confocal and electron microscopy and proteomic and genomic analyses.
Selected Publications
- Ewa Markiewicz, Rachel Venables, Mauricio-Alvarez-Reyes, Roy Quinlan, Margareth Dorobek Irena Hausmanowa-Petrucewicz & Christopher Hutchison (2002). Increased solubility of lamins and redistribution of lamin C in X-linked Emery Dreifuss Muscular Dystrophy Fibroblasts. J. Struct. Biol
- CMLJ Tilli, FCS Ramaekers, JLV Broers, CJ Hutchison & HAM Neumann (2002). Lamin Expression in Normal Human Skin, Actinic Keratosis, Squamous Cell Carcinoma and Basal Cell Carcinoma. Br. J. Dermatol
- Hutchison, CJ. (2002). Lamins: building blocks or regulators of gene expression? Nature Reviews: Molecular Cell Biology 3: 848 - 857.
- Ewa Markiewicz, Thomas Dechat, Roland Foisner, Roy. A Quinlan & Christopher J. Hutchison (2002). The lamin A/C binding protein LAP2a is required for the nuclear anchorage of the retinoblastoma protein. Mol. Biol. Cell
Journal papers: academic
- Pekovic, V., Gibbs-Seymour, ID., Markiewicz, E., Alzoghaibi, F., Benham, AM., Edwards, R., Wehnert, M., von Zlignicki, T. & Hutchison, CJ (2011). Conserved cysteine residues in the lamin A tail are essential for cellular responses to ROS generation. Aging Cell 10(6): 1067-1079.
- Richards, SA., Muter, J., Ritchie, P., Lattanzi, G. & Hutchison, CJ. (2011). The accumulation of un-repairable DNA damage in laminopathy progeria fibroblasts is caused by ROS generation and is prevented by treatment with N-acetyl cysteine . Human Molecular Genetics 20(20): 3997-4004.
- Tilgner, K., Wojciechowicz, K., Jahoda, C., Hutchison, C. & Markiewicz, E. (2009). Dynamic complexes of A-type lamins and emerin influence adipogenic capacity of the cell via nucleocytoplasmic distribution of {beta}-catenin. Journal of Cell Science 122(3): 401-413.
- Willis, ND., Cox, TR., Rahman-Casans, F., Smit, K., Przyborski, SA., van den Brandt, P., van Engeland, M., Weijenberg, M., Wilson, R., de Bruine, A. & Hutchison, CJ. (2008). Lamin A/C is a risk biomarker in colorectal cancer. PLoS ONE 3(8): e2988.
- Salpingidou, G., Rzepecki, R., Kiseleva, E., Lyon, C., Lane, E., Fusiak, K., Golebieska,A., Drummond, S., Allen, T., Ellis, JA., Smythe, C., Goldberg, M & Hutchison, CJ. (2008). NEP-A and NEP-B both contribute to nuclear pore formation in Xenopus eggs and oocytes. Journal of Cell Science 121(5): 706-716.
- Salpingidou, G, Smertenko, A, Hausmanowa-Petrucewicz, I, Hussey, PJ & Hutchison, CJ (2007). A novel role for the nuclear membrane protein emerin in association of the centrosome to the outer nuclear membrane. Journal of Cell Biology 178(6): 897-904.
- Pekovic, V, Harborth, J, Broers, JLV, Ramaekers, FCS, van Engelen, B, Lammens, M, von Zglinicki, T, Foisner, R, Hutchison, C & Markiewicz, E (2007). Nucleoplasmic LAP2 alpha-lamin A complexes are required to maintain a proliferative state in human fibroblasts. Journal Of Cell Biology 176(2): 163-172.
- Dorner, D, Vlcek, S, Foeger, N, Gajewski, A, Makolm, C, Gotzmann, J, Hutchison, CJ & Foisner, R (2006). Lamina-associated polypeptide 2 alpha regulates cell cycle progression and differentiation via the retinoblastoma-E2F pathway. Journal Of Cell Biology 173(1): 83-93.
- Broers, JLV, Ramaekers, FCS, Bonne, G, Ben Yaou, R & Hutchison, CJ (2006). Nuclear lamins: Laminopathies and their role in premature ageing. Physiological Reviews 86(3): 967-1008.
- Markiewicz, E, Tilgner, K, Barker, N, van de Wetering, M, Clevers, H, Dorobek, M, Hausmanowa-Petrusewicz, I, Ramaekers, FCS, Broers, JLV, Blankesteijn, WM, Salpingidou, G, Wilson, RG, Ellis, JA & Hutchison, CJ (2006). The inner nuclear membrane protein Emerin regulates beta-catenin activity by restricting its accumulation in the nucleus. EMBO Journal 25(14): 3275-3285.
- Markiewicz, E, Ledran, M & Hutchison, CJ (2005). Remodelling of the nuclear lamina and nucleoskeleton is required forskeletal muscle differentiation in vitro. Journal Of Cell Science 118(2): 409-420.
- Markiewicz, E, Dechat, T, Foisner, R, Quinlan, RA & Hutchison, CJ (2002). Lamin A/C binding protein LAP2 alpha is required for nuclear anchorageof retinoblastoma protein. Molecular Biology Of The Cell 13(12): 4401-4413.