Genetic and epigenetic mechanisms regulating neuronal development and function, with a particular interest in disruptions in these mechanisms that cause neurodevelopmental and cognitive disorders.
Research in the MacDonald lab focuses on understanding how transcriptional and epigenetic regulators act at the interface between genes and the environment, translating exposure to extrinsic factors into distinct neuronal phenotypes. Extensive research into neuronal disorders highlights that genetics alone fail to account for many of these complex syndromes, leading to growing evidence that epigenetics and gene-environment interactions play critical roles in neuronal development and cognitive function. We employ in vivo and in vitro animal models, and an array of molecular and cellular biological and microscopy approaches, to study how different genetic disruptions and environmental/ nutritional factors modify neuronal development and function, throughout the lifespan of an organism.
One current area of research focuses on the neurological disorder Rett Syndrome, caused by mutations in the epigenetic regulator MeCP2. Focusing on neurons within the neocortex, we are identifying molecular and cellular pathways that are disrupted in this disorder, and investigating potential therapeutic interventions of these perturbations, including by defined dietary supplementation. The ultimate goal of this research is to understand how life-long environmental exposures intersect with fixed genetic susceptibilities to alter neuronal development and cognitive function.
- Postdoctoral Fellow, Department of Stem Cell and Regenerative Biology, Harvard University (2008-2015)
- Ph.D., Neuroscience, University of British Columbia (2008)
- Hons. B.Sc., University of Toronto (2001)
- MacDonald, J.L.*§ & Fame, R.M*., Gillis-Buck, E.M., and Macklis, J.D.§ (2018) Caveolin 1 identifies a specific subpopulation of cerebral cortex callosal projection neurons (CPN) including dual projecting cortical callosal/frontal projection neurons (CPN/FPN). eNeuro, 5(1):1-17. *Co-first authors, §Co-corresponding authors
- Fame, R.M.* & MacDonald, J.L.*, Dunwoodie, S.L., Takahashi, E., and Macklis, J.D. (2016) Cited2 regulates neocortical layer II/III generation and somatosensory callosal projection neuron development and connectivity. Journal of Neuroscience. 36(24):6403-6419 (with cover). *Co-first authors
- Kishi, N.* & MacDonald, J.L.*, Ye, J., Molyneaux, B.J., Azim, E., and Macklis, J.D. (2016) Reduction of aberrant NF-kB signalling ameliorates Rett Syndrome phenotypes in Mecp2-null mice. Nature Communications. 7:10520. *Co-first authors
- MacDonald, J.L.* & Fame, R.M.*, Azim, E., Shnider, S.J., Molyneaux, B.J., Arlotta, P., and Macklis, J.D. (2013) Specification of cortical projection neurons: transcriptional mechanisms. Comprehensive Developmental Neuroscience: Patterning and Cell Type Specification in the Developing CNS and PNS. Vol.1:475-502. Editors J.L.R Rubenstein and P. Rakic. Elsevier. *Co-first authors.
- Fame, R.M.* & MacDonald, J.L.*, and Macklis, J.D. (2011) Development, specification, and diversity of callosal projection neurons. Trends in Neurosciences. 34(1):41-50. *Co-first authors.
- MacDonald, J.L., Berndt, A., Verster, A., and Roskams, A.J. (2010) MBD2 and MeCP2 regulate distinct transitions in the stage-specific differentiation of olfactory receptor neurons. Molecular and Cellular Neuroscience. 44:55-67.
- Molyneaux, B.J.*, Arlotta, P.*, Fame, R.M.†, MacDonald, J.L.†, MacQuarrie, K.L., and Macklis, J.D. (2009) Novel subtype-specific genes identify distinct subpopulations of callosal projection neurons. Journal of Neuroscience. 29(39):12343-54 (with cover). *Co-first authors; †Co-second authors.
- MacDonald, J.L. and Roskams, A.J. (2009) Epigenetic regulation of nervous system development by DNA methylation and histone deacetylation. Progress in Neurobiology. 88(3):170-83.
- MacDonald, J.L. and Roskams, A.J. (2008) Histone Deacetylases 1 and 2 are expressed at distinct stages of neuro-glial development. Developmental Dynamics. 237(8):2256-2267.
- MacDonald, J.L., Gin, C., and Roskams, A.J. (2005) Stage-specific induction of DNA methyltransferases in olfactory receptor neuron development. Developmental Biology. 288(2):461-73.