My research programme will attempt to understand the pathophysiology of Alzheimer’s disease, specifically focusing on the weakening of synaptic connections in the brain and to identify potential therapeutic targets. The aim of my research is to explore a key question: which factors modulate the cellular and molecular mechanisms of synapse weakening? To investigate this, we use a combination of innovative gene-transcription regulation, advanced imaging tools and neurophysiological approaches, which will determine whether and how functional and morphological synapse weakening is a critical step in the early pathophysiology of dementias.

Please see my  Research Staff Profile  for more detail

Key publications:

• Hughes et al., 2020. Aβ aggregates induce sensitised TLR4 signalling causing LTP deficit and neuronal cell death. Nature Commun Biol.
• Park et al., 2018. Impairment of release site clearance within the active zone by reduced SCAMP5 expression causes short-term depression of synaptic release. Cell Report.
• Regan et al., 2015. Tau phosphorylation at serine 396 residue is required for hippocampal LTD. Journal of Neuroscience.
• Jo et al., 2011. Aβ 1–42 inhibition of LTP is mediated by a signaling pathway involving caspase-3, Akt1 and GSK-3β. Nature Neuroscience.
• Li et al., 2010. Caspase-3 activation via mitochondria is required for long-term depression and AMPA receptor internalization. Cell.

Key collaborators:

• Prof David Klenerman, UK DRI at Cambridge
• Prof Chris Shaw, UK DRI at King's
• Dr Sarah Mizielinska, UK DRI at King's
• Dr Mathew Horocks, UK DRI at Edinburgh