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Professor Michael Coleman

University Position
Professor

Interests

We study axon degeneration and its roles in neurodegenerative disease. One focus is proteins regulating the degeneration of injured axons (?Wallerian degeneration'), which we have linked into a molecular pathway. Disease models involving similar mechanisms include several of peripheral neuropathies, Parkinson?s disease, glaucoma, motor neuron disease and multiple sclerosis. We aim to completely characterize the Wallerian pathway, identify human diseases associated with it and develop drugs to modify it. A second major interest is axonal pathology in Alzheimer?s disease. Using a new organotypic hippocampal slice culture model, we are studying the earliest pathogenic events in amyloid pathology and their dependence on Abeta and tau. We are collaborating on ALS, traumatic brain injury, neuropathic pain and white matter damage in Alzheimer?s disease. Finally, we have a developing interest in roles that rare axonal disease genes could play in axon survival in more common disorders.

Key Publications

Schwann cells are axo-protective after injury irrespective of myelination status in mouse Schwann cell/neuron cocultures.

DOI: http://doi.org/10.1242/jcs.261557
Journal: J Cell Sci
E-pub date: 15 Sep 2023
Authors: C Mutschler, SV Fazal, N Schumacher, A Loreto, MP Coleman, P Arthur-Farraj

SARM1 detection in myelinating glia: sarm1/Sarm1 is dispensable for PNS and CNS myelination in zebrafish and mice.

DOI: http://doi.org/10.3389/fncel.2023.1158388
Journal: Front Cell Neurosci
E-pub date: 1 Aug 2023
Authors: SV Fazal, C Mutschler, CZ Chen, M Turmaine, C-Y Chen, Y-P Hsueh, A Ibañez-Grau, A Loreto, A Casillas-Bajo, H Cabedo, RJM Franklin, RA Barker, KR Monk, BJ Steventon, MP Coleman, JA Gomez-Sanchez, P Arthur-Farraj

Enrichment of SARM1 alleles encoding variants with constitutively hyperactive NADase in patients with ALS and other motor nerve disorders.

DOI: http://doi.org/10.7554/eLife.70905
Journal: Elife
E-pub date: 19 Nov 2021
Authors: J Gilley, O Jackson, M Pipis, MA Estiar, A Al-Chalabi, MC Danzi, KR van Eijk, SA Goutman, MB Harms, H Houlden, A Iacoangeli, J Kaye, L Lima, Queen Square Genomics, J Ravits, GA Rouleau, R Schüle, J Xu, S Züchner, J Cooper-Knock, Z Gan-Or, MM Reilly, MP Coleman

A Novel NAD Signaling Mechanism in Axon Degeneration and its Relationship to Innate Immunity.

DOI: http://doi.org/10.3389/fmolb.2021.703532
Journal: Front Mol Biosci
E-pub date: 1 Aug 2021
Authors: EL Hopkins, W Gu, B Kobe, MP Coleman

Homozygous NMNAT2 mutation in sisters with polyneuropathy and erythromelalgia.

DOI: http://doi.org/10.1016/j.expneurol.2019.112958
Journal: Exp Neurol
E-pub date: 1 Oct 2019
Authors: P Huppke, E Wegener, J Gilley, C Angeletti, I Kurth, JPH Drenth, C Stadelmann, A Barrantes-Freer, W Brück, H Thiele, P Nürnberg, J Gärtner, G Orsomando, MP Coleman

Severe biallelic loss-of-function mutations in nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2) in two fetuses with fetal akinesia deformation sequence.

DOI: http://doi.org/10.1016/j.expneurol.2019.112961
Journal: Exp Neurol
E-pub date: 1 Oct 2019
Authors: M Lukacs, J Gilley, Y Zhu, G Orsomando, C Angeletti, J Liu, X Yang, J Park, RJ Hopkin, MP Coleman, RG Zhai, RW Stottmann

Publications

SARM1 is a multi-functional NAD(P)ase with prominent base exchange activity, all regulated bymultiple physiologically relevant NAD metabolites.

DOI: http://doi.org/10.1016/j.isci.2022.103812
Journal: iScience
E-pub date: 18 Feb 2022
Authors: C Angeletti, A Amici, J Gilley, A Loreto, AG Trapanotto, C Antoniou, E Merlini, MP Coleman, G Orsomando

Sarm1 haploinsufficiency or low expression levels after antisense oligonucleotides delay programmed axon degeneration.

DOI: http://doi.org/10.1016/j.celrep.2021.110108
Journal: Cell Rep
E-pub date: 14 Dec 2021
Authors: SA Gould, J Gilley, K Ling, P Jafar-Nejad, F Rigo, M Coleman

Neurotoxin-mediated potent activation of the axon degeneration regulator SARM1.

DOI: http://doi.org/10.7554/eLife.72823
Journal: Elife
E-pub date: 6 Dec 2021
Authors: A Loreto, C Angeletti, W Gu, A Osborne, B Nieuwenhuis, J Gilley, E Merlini, P Arthur-Farraj, A Amici, Z Luo, L Hartley-Tassell, T Ve, LM Desrochers, Q Wang, B Kobe, G Orsomando, MP Coleman

NAD+ cleavage activity by animal and plant TIR domains in cell death pathways.

DOI: http://doi.org/10.1126/science.aax1911
Journal: Science
E-pub date: 23 Aug 2019
Authors: S Horsefield, H Burdett, X Zhang, MK Manik, Y Shi, J Chen, T Qi, J Gilley, J-S Lai, MX Rank, LW Casey, W Gu, DJ Ericsson, G Foley, RO Hughes, T Bosanac, M von Itzstein, JP Rathjen, JD Nanson, M Boden, IB Dry, SJ Williams, BJ Staskawicz, MP Coleman, T Ve, PN Dodds, B Kobe

Low levels of NMNAT2 compromise axon development and survival.

DOI: http://doi.org/10.1093/hmg/ddy356
Journal: Hum Mol Genet
E-pub date: 1 Feb 2019
Authors: J Gilley, PR Mayer, G Yu, MP Coleman

Neuronal Cell Death.

DOI: http://doi.org/10.1152/physrev.00011.2017
Journal: Physiol Rev
E-pub date: 1 Apr 2018
Authors: M Fricker, AM Tolkovsky, V Borutaite, M Coleman, GC Brown

Sarm1 Deletion, but Not WldS, Confers Lifelong Rescue in a Mouse Model of Severe Axonopathy.

DOI: http://doi.org/10.1016/j.celrep.2017.09.027
Journal: Cell Rep
E-pub date: 3 Oct 2017
Authors: J Gilley, RR Ribchester, MP Coleman

NMN Deamidase Delays Wallerian Degeneration and Rescues Axonal Defects Caused by NMNAT2 Deficiency In Vivo.

DOI: http://doi.org/10.1016/j.cub.2017.01.070
Journal: Curr Biol
E-pub date: 20 Mar 2017
Authors: M Di Stefano, A Loreto, G Orsomando, V Mori, F Zamporlini, RP Hulse, J Webster, LF Donaldson, M Gering, N Raffaelli, MP Coleman, J Gilley, L Conforti

A rise in NAD precursor nicotinamide mononucleotide (NMN) after injury promotes axon degeneration.

DOI: http://doi.org/10.1038/cdd.2014.164
Journal: Cell Death Differ
E-pub date: 1 May 2015
Authors: M Di Stefano, I Nascimento-Ferreira, G Orsomando, V Mori, J Gilley, R Brown, L Janeckova, ME Vargas, LA Worrell, A Loreto, J Tickle, J Patrick, JRM Webster, M Marangoni, FM Carpi, S Pucciarelli, F Rossi, W Meng, A Sagasti, RR Ribchester, G Magni, MP Coleman, L Conforti

Absence of SARM1 rescues development and survival of NMNAT2-deficient axons.

DOI: http://doi.org/10.1016/j.celrep.2015.02.060
Journal: Cell Rep
E-pub date: 31 Mar 2015
Authors: J Gilley, G Orsomando, I Nascimento-Ferreira, MP Coleman

Wallerian degeneration: an emerging axon death pathway linking injury and disease.

DOI: http://doi.org/10.1038/nrn3680
Journal: Nat Rev Neurosci
E-pub date: 1 Jun 2014
Authors: L Conforti, J Gilley, MP Coleman

Rescue of peripheral and CNS axon defects in mice lacking NMNAT2.

DOI: http://doi.org/10.1523/JNEUROSCI.1534-13.2013
Journal: J Neurosci
E-pub date: 14 Aug 2013
Authors: J Gilley, R Adalbert, G Yu, MP Coleman