Babraham Institute: Laboratory for Signalling and Cell fate
Tel. (01223) 496315
1982-1986 B.A. (Hons.) Biochemistry, University of Oxford
1986-1989 Ph.D. St. George’s Hospital Medical School, University of London
1989-1994 Postdoc, Institute of Molecular Medicine, University of Oxford.
1994-1999 Senior postdoc, Department of Pharmacology, University of Oxford.
1999-2003 Independent Group Leader, Center for Molecular Medicine (ZMMK), University of Cologne
Since 2003 Group Leader, The Babraham Institute, Cambridge, UK (and since 2007 external member of Cambridge Centre for Brain Repair)
How do axons die?
Mechanisms of cell death are now reasonably well understood, but axons are a highly specialised part of neuronal cells and little is known about how they die. Michael Coleman is studying the molecular mechanism of Wallerian degeneration, a form of programmed axonal death, which is triggered by diverse degenerative stimuli including nerve injury, genetic defects of myelination and protein turnover, and toxic or genetic blockade of axonal transport.
To understand mechanisms of axon degeneration we need a reliable experimental model, such as Wallerian degeneration, the degeneration of axons distal to an injury. First described in 1850 by Augustus Waller, and named after him, Wallerian degeneration is now opening up to molecular analysis and research in this area is revealing insights into the molecular mechanisms of neurodegeneration.
Studies focus on a mutant protein identified in our group, WldS, which delays Wallerian degeneration by tenfold in mutant mice, and on identifying other proteins in this regulatory pathway. We have now successfully transferred WldS to transgenic rats indicating that axons can be protected in other mammals. Indeed, the degree of synaptic protection in rats is greater than in mice, raising the possibility that WldS may be more beneficial in species with longer axons such as man.
Coleman MP, Freeman MR (In press) Wallerian degeneration, WLDs and Nmnat.
Annual Review of Neuroscience
Gilley J, Coleman MP (2010) Endogenous Nmnat2 is an essential survival factor for maintenance of healthy axons.
PLoS Biology 8 e1000300
Wong F, Fan L, Wells S, Hartley R, Mackenzie FE, Oyebode O, Brown R, Thomson D, Coleman MP, Blanco G, Ribchester RR (2009) Axonal and neuromuscular synaptic phenotypes in WldS, SOD1G93A and ostes mutant mice identified by fiber-optic confocal microendoscopy.
Molecular and Cellular Neuroscience 42 296-307
Conforti L, Wilbrey AL, Morreale G, Janeckova L, Beirowski B, Adalbert R, Mazzola F, Di Stefano M, Hartley R, Babetto E, Smith T, Gilley J, Billington RA, Genazzani AA, Ribchester RR, Magni G, Coleman MP (2009) WldS protein requires Nmnat activity and a short N-terminal sequence to protect axons in mice.
Journal of Cell Biology 184 491-500
Morreale G, Conforti L, Coadwell WJ, Wilbrey AL, Coleman MP (2009) Evolutionary divergence of valosin-containing protein/cell division cycle protein 48 binding interactions among endoplasmic reticulum-associated degradation proteins.
FEBS Journal 276 1208-1220
Beirowski B, Babetto E, Gilley J, Mazzola F, Conforti L, Janeckova L, Magni G, Ribchester RR, Coleman MP (2009) Non-nuclear WldS determines its neuroprotective efficacy for axons and synapses in vivo.
Journal of Neuroscience 29 653-668
Adalbert R, Nogradi A, Babetto E, Janeckova L, Walker SA, Kerschensteiner M, Misgeld T, Coleman MP (2009) Severely dystrophic axons at amyloid plaques remain continuous and connected to viable cell bodies.
Brain 132 402-416
Beirowski B, Babetto E, Coleman MP, Martin KR (2008) The WldS gene delays axonal but not somatic degeneration in a rat glaucoma model.
European Journal of Neuroscience 28 1166-1179
Wilbrey AL, Haley JE, Wishart TM, Conforti L, Morreale G, Beirowski B, Babetto E, Adalbert R, Gillingwater TH, Smith T, Wyllie DJA, Ribchester RR, Coleman MP (2008) VCP binding influences intracellular distribution of the slow Wallerian degeneration protein, WldS.
Molecular and Cellular Neuroscience 38 325-340
Bridge KE, Berg N, Adalbert R, Babetto E, Dias T, Spillantini M-G, Ribchester RR, Coleman MP (2009) Late onset distal axonal swelling in YFP-H transgenic mice.
Neurobiology of Aging 30 309-321
Adalbert R, Gilley J, Coleman MP (2007) Aβ, tau and ApoE4 in Alzheimer’s disease: the axonal connection.
Trends in Molecular Medicine 13 135-142
Conforti L, Adalbert R, Coleman MP (2007) Neuronal death: where does the end begin?
Trends in Neurosciences 30 159-166
Conforti L, Fang G, Beirowski B, Wang MS, Sorci L, Asress S, Adalbert R, Silva A, Bridge K, Huang XP, Magni G, Glass JD, Coleman MP (2007) NAD+ and axon degeneration revisited: Nmnat1 cannot substitute for WldS to delay Wallerian degeneration.
Cell Death and Differentiation 14 116-127
Adalbert R, Nogradi A, Szabo A, Coleman MP (2006) The slow Wallerian degeneration gene in vivo protects motor axons but not their cell bodies after avulsion and neonatal axotomy.
European Journal of Neuroscience 24 2163-2168
Laser H, Conforti L, Morreale G, Mack TGM, Heyer M, Haley JE, Wishart TM, Beirowski B, Walker SA, Haase G, Celik A, Adalbert R, Wagner D, Grumme D, Ribchester RR, Plomann M, Coleman MP (2006) The slow Wallerian degeneration protein, WldS, binds directly to VCP/p97 and partially redistributes it within the nucleus.
Molecular Biology of the Cell 17 1075-1084
Coleman MP (2005) Axon degeneration mechanisms: commonality amid diversity.
Nature Reviews Neuroscience 6 889-898
Adalbert R, Gillingwater TH, Haley JE, Bridge K, Beirowski B, Berek L, Wagner D, Grumme D, Thomson D, Celik A, Addicks K, Ribchester RR, Coleman MP (2005) A rat model of slow Wallerian degeneration (WldS) with improved preservation of neuromuscular synapses.
European Journal of Neuroscience 21 271-277
Mi W, Beirowski B, Gillingwater TH, Adalbert R, Wagner D, Grumme D, Osaka H, Conforti L, Arnhold S, Addicks K, Wada K, Ribchester RR, Coleman MP (2005) The slow Wallerian degeneration gene, WldS, inhibits axonal spheroid pathology in gracile axonal dystrophy mice.
Brain 128 405-416
Mack TGA, Reiner M, Beirowski B, Mi W, Emanuelli M, Wagner D, Thomson D, Gillingwater TH, Court F, Conforti L, Fernando FS, Tarlton A, Andressen C, Addicks K, Magni G, Ribchester RR, Perry VH, Coleman MP (2001) Wallerian degeneration of injured axons and synapses is delayed by a Ube4B/Nmnat chimeric gene.
Nature Neuroscience 4 1199-1206