The discovery of induced pluripotent stem cells (iPSCs) has revolutionised the neurodegeneration field. iPSCs provide the ability to take, typically, skin cells from people with Parkinson’s, convert them into iPSCs (which have the unique property to turn into any cell type) and differentiate them into dopamine neurons. Although being the best human model available, one limitation of current iPSC approaches is that dopamine neurons do not act alone in the human brain but interact with many other cell types. Therefore, the formation of more sophisticated iPSC models, where multiple brain cell types interact and we can study those interactions, is necessary for the drug discovery process. More sophisticated models will, ultimately, identify quality therapeutic candidates to put forward for clinical trials in the early treatment of Parkinson’s. Therefore, the overall goals of Charmaine's team are:
- Build complex iPSC-derived dopamine neuron and astrocyte co-culture models of Parkinson’s including through the use of microfluidic devices
- Interrogate the differences in function and communication (whether through axonal contact or extra-cellular vesicles) between dopamine neurons and astrocytes in Parkinson’s and dementia
- Identify, screen and validate therapeutic targets through unbiased RNA-seq approaches and mechanism-based study in these complex iPSC-derived Parkinson’s models
Several targets that Charmaine has developed in the laboratory are actively moving through the therapeutic pipeline from bench to bedside. Not only will this work identify potential new therapeutic targets and disease modifying drugs to treat Parkinson’s, but it will also lead on the development of new, more relevant “in a dish” models of mixed neuron/astrocyte co-cultures for mechanism based study and drug screening purposes that could enter widespread use.
Charmaine, originally from Sydney, Australia, obtained her undergraduate degree, a BSc (Hons I), from the University of New South Wales (UNSW). She then pursued a PhD at the Garvan Institute of Medical Research, working in the Parkinson’s and neurogenomics lab, where she investigated the relationship between alpha synuclein and mitochondrial dysfunction in Idiopathic Parkinson’s. After completing her PhD, Charmaine moved to Oxford for a post-doctoral position in the Richard Wade-Martins lab. She led the optimization of protocols for the differentiation of induced pluripotent stem cell (iPSC)-derived dopamine neurons and astrocytes. Recently, Charmaine was granted a Parkinson’s UK/Rostrees Trust Senior Research Fellowship to create and develop her own team focused on using these complex iPSC-derived dopamine neuron/astrocyte co-culture models to advance understanding of dopamine neuron astrocyte communication in Parkinson’s and to discover new therapeutic targets of interest.