null Keith Murai, PhD
neuroscience • brain • development • plasticity • neurodevelepmental disorders • neurodegenerative diseases • synapse • glia • astrocyte
My research has two main areas of focus: understanding how neurons and glial cells cooperate to regulate brain development and homeostasis, and discovering mechanisms that regulate the plasticity of synapses underlying memory formation, neurodevelopmental disorders and neurodegenerative diseases. My research uses advanced approaches, including neuronal/astrocyte-specific and time-controlled gene deletion in mice, manipulations including in utero electroporation (IUE) and viral gene delivery, confocal/2-photon imaging, and behavioural analysis. It also incorporates human postmortem tissue analysis (Alzheimer’s disease and Down syndrome) and human-induced pluripotent stem cell (hiPSC) technologies (Down syndrome) to advance the understanding of neuronal and astrocytic alterations in brain disorders and diseases. These approaches are complemented with cellular and tissue mRNA profiling and bioinformatics methods to understand how specific genetic manipulations impact the molecular features of neurons and astrocytes in the brain.
C. Salmon, H. Pribiag, S. Cameron, C. Gizowski, V. Mahadevan, D. Stellwagen, C. W. Bourque, M. A. Woodin, and K.K. Murai (2020). Depolarizing GABA transmission restrains excitatory synapse formation in the developing hippocampus. Frontiers in Cellular Neuroscience, 14:36.
B. Ponroy Bally, W. T. Farmer*, E. V. Jones, S. Jessa, J. Benjamin Kacerovsky, A. Mayran, H. Peng, J. L. Lefebvre, J. Drouin, A. Hayer, C. Ernst, and K. K. Murai. Human iPSC-derived Down syndrome astrocytes display genome-wide perturbations in gene expression, an altered adhesion profile, and increased cellular dynamics (2020). Human Molecular Genetics, 29:785-802.
W. T. Farmer*, T. Abrahamsson, S. Chierzi*, C. Lui*, C. Zaelzer, E.V. Jones*, B. Ponroy Bally*, G. C. Chen, J. F. Théroux, J. Peng, C. W. Bourque, F. Charron, C. Ernst, P. J. Sjöström, and K.K. Murai (2016). Neurons diversify astrocytes in the adult brain through Sonic hedgehog signaling. Science, 351:849-54.
D. S. Bouvier*, E. V. Jones*, G. Quesseveur*, M. A. Davoli, T. Alves-Ferreira, R. Quirion, N. Mechawar, and K. K. Murai (2016). High resolution dissection of cooperative microglial-astrocyte remodeling in Alzheimer's disease. Scientific Reports, 6:24544.
D. Cook*#, E. Nuro*#, E.V. Jones*, H.F. Altimimi, W.T. Farmer*, V. Gandin, E. Hanna*, R. Zong, A. Barbon, D.L. Nelson, I. Topisirovic, J. Rochford, D. Stellwagen, J-C. Béïque and K.K. Murai (2014). FXR1P limits long-term memory, long-lasting synaptic potentiation, and de novo GluA2 translation (#equal contributions). Cell Reports, 9:1402-16.