The Denham laboratory is investigating how genetic variations can contribute to the risk of developing Parkinson's disease (PD). In particular, they are studying GBA-associated PD, to identify novel genetic mutations that affect signalling pathways during disease states. The laboratory uses patient-specific neurons derived from induced pluripotent stem cells to examine these processes.
Investigating genetic causes of Parkinson’s disease using stem cell-derived neurons.
Heterozygous mutations in the gene GBA are the most prevalent genetic risk factor for familial PD. GBA encodes the glucocerebrosidase enzyme that functions in the lysosomes and a dysfunctional autophagy-lysosomal pathway can result in the accumulation of proteins including Alpha-synuclein, increasing the risk of developing pathological protein aggregates, which is the hallmark of PD. Our laboratory uses induced pluripotent stem cells (iPSCs) reprogrammed from GBA heterozygous patients to investigate the changes in neurons that occur during the early stages of Parkinson’s disease.
Induced pluripotent stem cell culture, differentiation of IPSCs into neurons, Immunofluorescence, lentiviral delivery of transgenes, CRISPR, neuronal activity analysis using a multi-electrode array, RNA sequencing analysis.
Please contact Group Leader Mark Denham directly, if interested.