Signaling pathways to degeneration and resilience

Our laboratory is focussed in the molecular mechanisms of core interdependent pathological processes upon which several neurological disorders, including ALS, converge, including oxidative stress, mitochondrial dysfunction, inflammation, and abberant Ca²⁺ handling. Additionally, we are interested in the brain's capacity for homeostasis, particularly the ability of neurons and astrocytes to mount adaptive protective responses to adverse conditions.

For example, we contribute to knowledge of the molecular mechanisms underlying both the neuroprotective and neurodestructive effects of Ca²⁺ signals, as well as the factors that determine whether signals are harmful or beneficial. The coordinated transcriptional changes that underlie Ca²⁺-dependent neuroprotective effects are also a focus, including new investigations into Ca²⁺-dependent transcriptional control in human stem cell-derived neurons. In addition, we research into molecular mechanisms of Ca²⁺-mediated excitotoxicity involving NMDA receptor channel subunit composition and mitochondrial dysfunction. Another core interest is the key neuroprotective role played by astrocytes  and how neurons may communicate their needs to them. More recently, we have been investigating  with collaborators the impact of disease pathology on astrocytic function and how this in turn impacts on neuronal properties.