Imperial College London
Department of Medicine
My research interest lies within neurodegenerative disease, and understanding mechanisms of neuronal demise, to design improved therapeutic strategies for tackling these devastating disorders. In particular, my work focuses on the use of toxin-induced animal models of neurodegeneration and post-mortem human tissue taken from patients who suffered from neurodegenerative disorders, including Alzheimer’s disease and Parkinson’s disease (PD). I collaborate with Prof. David Dexter at Imperial, with whom I supervise PhD students, as well as with investigators at Newcastle University, Cambridge University and King's College London, to investigate the effects of deep-brain stimulation (DBS) on brain targets such as the pedunculopontine nucleus (PPN) and subthalamic nucleus (STN) in both animal models of PD and in post-mortem human tissue. This technique, when delivered at low frequency (~20 Hz), in the case of the PPN, and at high frequency (~80 Hz) for the STN, has proved immensely beneficial when delivered to PD patients, who prove refractory to other dopaminergic therapies. However, despite the ever-increasing use of this surgical technique, the underlying neuronal substrate that gives rise to the clinical benefits remains very poorly understood. To enlighten on this, I make use of post-mortem human tissue analyses, powerful Designer Receptors Exclusively Activated by Designer Ligands (DREADDs), combined with animal modelling, 2-photon microscopy, Positron Emission tomography (PET) imaging and molecular analyses performed on tissue, to better understand which neuronal and/or non-neuronal cellular subtypes might be responsible for DBS-induced clinical benefits seen in PD patients.
I further have an interest in whole-genome sequencing approaches for identifying novel therapeutic targets. In this regard, I collaborate with Prof. Richard Reynolds at Imperial and Dr. Joanna Elson at Newcastle University, using well-characterised post-mortem brain tissue obtained from Multiple Sclerosis patients. I also have several collaborations for applying whole-genome sequencing methodologies, including at the single-cell level to PD and Alzheimer's disease brain samples. In this regard, I am particularly interested in the role of mitochondrial dynamics to the processes underlying neurodegeneration.
Another theme in my research is the synthesis and testing of novel compounds, especially those capable of chelating excess metals in the brains of neurodegenerative disease patients. For this, I collaborate with medicinal chemists and research groups at the Universities of Aberdeen, Konstanz and Strassbourg.
University of Northumbria at Newcastle
Department of Applied Sciences
I aim to understand the molecular and cellular mechanisms for the motor and non-motor features of neurodegenerative disease. Using tools such as G-protein coupled receptors to modulate neuronal activity, the overall goal is to develop new tools (pharmacological and viral vector based) to reverse the biochemical changes underlying the behavioral deficits associated with such diseases.