Glia-Neuron Cross-Talk in iPSC Model(s) of Induced Neurodegeneration
Sam Patel is a postdoctoral fellow at the Department of Neurology, at UCLA. His research aims to dissect key gene networks (modules) altered in brain areas that show signs of neurodegeneration. He utilizes cutting-edge ipsc technology, Crispr/cas9 tools, and HTS platforms to discover and validate the crosstalk signaling pathways between neurons and process-bearing glial cells in the context of neurodegeneration.
In order to recapitulate-in-a-dish adult-like disease states, at Geschwind/Rexach labs, Sam will utilize “induced pluripotent stem cell technology” derived cells (ipsc) from healthy individuals and patients carrying mutation in neurodegeneration-associated genes (eg. MAPT) which are already available in the lab. Taking advantage of the ability of ipsc to give rise to any cell subtype, He will firstly (1) coax them into becoming cells resembling those in human brain i.e. Astrocytes, oligodendrocytes and neurons,(2) followed by aggregating them in a 3D tissue like aggregate. (3) Subsequently, the spheroids will be sectioned and immunohistochemically labeled to visually demarcate regions where astrocyte-oligodendrocytes-neurons segregate as a unit. (4) From hereon, DSP will allow us to readout both the RNA population and the protein contents of each interacting cell type. In brief, our aim is to understand how a mutation carrying astrocyte modulate and alters the transcriptome and proteome of its neighboring neurons and/oligodendrocyte.
Lastly, the findings from 3D neuro-spheroid studies will be validated in well-characterized postmortem human FTD samples to construct the astrocyte-neuron-oligodendrocyte “interactome” underlying normal aging and the changes that lead to dementia. This project could identify potential novel therapeutic targets to alleviate neuron’s degeneration and rescue/restore neuronal function by modulating disrupted pathways in astrocytes and oligodendrocytes.