My lab focusing on investigating the cellular and molecular mechanisms which make motor neurons vulnerable to degeneration, with a specific interest in the childhood motor neuron disease Spinal Muscular Atrophy.
Our work aims to understand the both reasons why motor neurons are vulnerable and what mechanisms contribute to their degeneration.
It is our hope that by understanding these processes we can develop ways in which to protect motor neurons in a variety of pathological contexts.
More specifically, one of our current projects is centred on transcriptional profiling of differentially vulnerable motor neurons.
This project is based on the observation that in both patients and mouse models of SMA, not all motor units are equally affected with some showing high levels of degeneration whilst others remain relatively intact.
We therefore use laser capture micro-dissection to isolate differentially vulnerable motor neuron populations and perform transcriptional analysis to investigate the underlying difference between differentially vulnerable populations.
This project aims to both address the molecular and cellular changes which are associated with the onset of motor neuron degeneration, and those which are associated with motor neuron protection.
Bowerman M, Michalski JP, Beauvais A, Murray LM, Derepentigny Y, Kothary R. (2014) Defects in pancreatic development and glucose metabolism in SMN-depleted mice independent of canonical spinal muscular atrophy neuromuscular pathology. Hum Mol Genet. In Press
Boyer JG, Deguise MO, Murray LM, Yazdani A, De Repentigny Y, Boudreau-Larivière C, Kothary R. (2014) Myogenic program dysregulation is contributory to disease pathogenesis in spinal muscular atrophy. Hum Mol Genet. In Press
Boyer JG., Murray LM, Scott K., De Repentigny Y., Renaud JM., Kothary R., (2013) Early onset muscle weakness and disruption of muscle proteins in mouse models of spinal muscular atrophy. Skeletal Muscle. 3:24.
Murray, LM., Gillingwater TH., Kothary R., (2013) Dissection of the mouse transversus abdominis muscle for whole-mount neuromuscular junction analysis. J Vis Exp. 83:e51162
Sanchez G., Dury A., Murray, LM., Biondi O., Tadesse, H., Kothary R., Khandjian E., Charbonnier F., Côté Jocelyn. (2013) A Novel Function for the Survival Motoneuron Protein as a Translational Regulator. Hum Mol Genet. 22:668-84.
Murray LM., Beauvais A., Bhanot K. and R., K. (2012) Defects in Neuromuscular Junction Remodelling in the Smn2B/- Mouse Model of Spinal Muscular Atrophy. Neurobiology of disease, 49C: 57-67
Bowerman M., Murray LM., Anderson CL., Kothary R. (2012) Fasudil increases survival and restores neuromuscular junction and skeletal muscle development in a spinal muscular atrophy mouse model. BMC Medicine. 2012 10:24-38
Bowerman MB., Murray LM., Beauvais A, Pinero B, Kothary R. (2012) A critical Smn threshold dictates onset of an intermediate Spinal Muscular Atrophy phenotype associated with a distinct neuromuscular junction pathology. Neuromuscular Disorders. 22:263-76
Mutsaers C, Wishart TM, Lamont DJ, Riessland M, Schreml J, Comley LH, Murray LM, Parson SH, Lochmüller H, Wirth B, Talbot K, Gillingwater TH. (2011) Reversible molecular pathology of skeletal muscle in spinal muscular atrophy. Hum Mol Genet. 20:4334-44
Comley LH., Wishart TM., Baxter B., Murray LM., Nimmo A., Thomson D., Parson SH., Gillingwater TH., (2011) Induction of cell stress in neurons from transgenic mice expressing yellow PLoSOne 6:e17639
Murray LM., Comely LH., Gillingwater TH., Parson SH. (2011) The response of neuromuscular junctions to injury is developmentally regulated. FASEB J. 25:1306-13
Wishart TM*., Huang JPW*., Murray LM*., Lamont DJ., Mutsaers CM., Ross J., Geldsetzer P., Ansorge O., Talbot K., Parson SH., Gillingwater TH. (2010) SMN deficiency disrupts brain development in a mouse model of severe spinal muscular atrophy. Hum Mol Genet. 19:4216-28 Murray LM.,Gillingwater TH., Parson SH. (2010) Using mouse cranial muscles to investigate neuromuscular pathology in vivo. Neuromuscular disorders. 20: 740-743
Murray LM, Lee S, Bäumer D, Parson SH, Talbot K, Gillingwater TH.(2010) Pre-symptomatic development of lower motor neuron connectivity in a mouse model of severe spinal muscular atrophy.Hum Mol Genet.19:420-423
Bäumer D, Lee S, Davies J, Nicholson G, Parkinson NJ, Murray LM, Gillingwater TH, Davies KE, Talbot K. (2009) Alternative splicing events are a late feature of pathology in a mouse model of Spinal Muscular Atrophy. PLoS Genetics. 5:e1000773
Murray LM, Talbot K, Gillingwater TH. (2010) Neuromuscular Synaptic Vulnerability in Motor Neuron Disease: Amyotrophic Lateral Sclerosis and Spinal Muscular Atrophy. NeuropatholApplNeurobiol. 36:133-156
Soriano FX, Baxter P, Murray LM, Sporn MB, Gillingwater TH, Hardingham GE.(2008) Transcriptional regulation of the AP-1 and Nrf2 target gene sulfiredoxin.Oxidative Medicine and Cellular Longevity.27:179-283.
Murray LM, Thomson D, Conklin A, Wishart TM, Gillingwater TH (2008) Loss of translation elongation factor (eEF1A2) expression in vivo differentiates between Wallerian degeneration and dying-back neuronal pathology. J Anat. 213:633-45.
Murray LM, Comley LH, Thomson D, Parkinson N, Talbot K, GillingwaterTH (2008) Selective vulnerability of motor neurons and dissociation of pre- and post-synaptic pathology at the neuromuscular junction in mouse models of spinal muscular atrophy. Hum Mol Genet.17:949-62.