Research
Research Interests
Neurodegenerative diseases including Alzheimer's disease and Parkinson's disease are a global public health priority, affecting millions of people worldwide. We are in urgent need of early-stage diagnostic markers and new therapeutic targets to treat these diseases. My lab aims to meet these needs through understanding the potential role of the endosomal system in neurodegenerative pathology.
The Endosomal System
The endosomal system comprises an inter-connected series of intracellular membrane-bound compartments controlling protein and lipid transport. Perturbation of the endosomal system has been implicated in the initiation and progression of several neurodegenerative disorders with neuronal endosomal swelling classed as an early hallmark of disease. Retromer is an endosomal trimeric complex important for regulating the retrieval and trafficking of numerous proteins away from the degradative pathway. Retromer expression is significantly decreased in Alzheimer's patients, and mutations have been found in Parkinson's patients. Retromer associates with sorting nexin-27 (SNX27) when trafficking specific proteins to the cell surface, critical for cells communicating with their extracellular environment. SNX27 dysfunction has been implicated in Down’s syndrome, which greatly increases the risk for developing Alzheimer's disease. We are interested in exploring the endosomal system and SNX27-Retromer in different cell types of the brain including neurons and astrocytes to understand how perturbation of this system can lead to disease. We use a range of techniques including cell biology, quantitative proteomics and biochemistry.
Interplay between Astrocytes and Neurons
Crucially, the role of the endosomal system in glial cells is unclear and understudied, leaving a critical gap in our knowledge. Astrocytes, a form of glial cells, are known to play an essential role in neuronal health and have been heavily implicated in neurodegenerative pathology. We are focused on understanding the role of the astrocytic endosomal system in astrocyte function, neuronal health and ultimately, neurodegenerative disease.