Kevin Charland

Ph.D. Candidate at Tufts University

My research involves developing 2D and 3D neural tri-culture models using the recombinant inbred BXD panel to discover novel genetic modifiers and therapeutics for neurodegenerative diseases. 2D in vitro models can serve as a valuable tool for certain applications (e.g., preliminary drug screens) but fall short in fully recapitulating proper cellular transcriptomics and disease phenotypes seen in vivo. The BXD panel leverages 2 classically recombinant inbred strains (C57BL/6J and DBA/2J) to generate extensive genomic diversity allowing for more precise identification of candidate genes/targets/drugs via genetic mapping and a readily manipulated genome. Alzheimer's disease (AD)-related cognitive decline has shown considerable variation across individuals with similar AD risk suggesting that genetic modifiers of AD-related cognitive decline are ripe for discovery. I plan to adapt preexisting protocols to generate 2D and 3D tri-culture in vitro models derived from BXD embryonic stem cells (ESCs) with or without the 5XFAD transgene for better investigation into genetic influences of AD-related pathologies as well as a screening platform for genetic targets and/or therapeutics. These protocols can then be applied to human patient-derived induced pluripotent stem cells (iPSCs) to extend pathology modeling into a human cell context and promote more precise identification of novel AD-related targets and therapeutics.

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