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Other Interdiciplinary Incentives

  • Neuroscience
  • Stem Cells
  • Research Focus

    Keywords

  • Microglia
  • iPSC
  • CRISPR-Cas9 Screens
  • Epigenetics
  • Human Genetics
  • Molecular Genetics
  • Clinical Conditions

  • Alzheimer's disease
  • Parkinson's disease
  • Equipment & Techniques

  • Cell culture
  • Bioreactors
  • Microscopy
  • Science Culture

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    Dr Sam Washer

    University Position
    Research Associate

    Interests

    I research the genomics of Alzheimer's disease and how genetic variation can impact the microglial response in neuroinflammation through genome wide CRISPR screening at the Wellcome Sanger Institute, in collaboration with the University of Oxford (Dr Sally Cowley, James Martin Stem Cell Facility and Prof Daniel Ebner, Target Discovery Institute) as part of Open Targets. I have developed a novel method for generating human microglia from iPSC models and novel assays for measuring uptake of dead neurons and other cargo into microglia. I have also optimized and developed methods for transducing iPSC microglia with lentiviral vectors for use in editing cells to introduce transgenes or genetic editing via CRISPR/Cas9. Combining these methods with the known genetics of Parkinson's and Alzheimer's Disease from genome-wide association studies (GWAS), I am performing CRISPR screens to link risk genetics to gene function in microglia. The overarching aim is to identify novel therapeutic pathways for the treatment of AD and PD. Outside CRISPR screening, I have an interest in cellular (iPSC models of neurodegeneration), molecular (gene editing techniques), and computational genetics (QTL analysis/scRNA-seq/long read), and how these can be combined to answer how genetics contribute to disease.

    Key Publications

    Single-cell transcriptomics defines an improved, validated monoculture protocol for differentiation of human iPSC to microglia

    DOI: https://doi.org/10.1038/s41598-022-23477-2
    Journal: Scientific Reports
    Year: 2022
    Authors: Washer SJ, Perez-Alcantara M, Chen Y, Steer J, James WS, Trynka G, Bassett AR, Cowley SA

    Publications

    Alternative splicing of jnk1a in zebrafish determines first heart field ventricular cardiomyocyte numbers through modulation of hand2 expression

    DOI: https://doi.org/10/1371/journal.pgen.1008782
    Journal: PLOS Genetics
    Year: 2020
    Authors: Santos-Ledo A, Washer S, Dhanaseelan T, Eley L, Alqatani A, Chrystal PW, Papoutsi T, Henderson DJ, Chaudhry B

    Genome-wide DNA methylation meta-analysis in the brains of suicide completers

    DOI: https://doi.org/10.1038/s41398-020-0752-7
    Journal: Translational Psychiatry
    Year: 2020
    Authors: Policicchio S, Washer S, Viana J, Iatrou A, Burrage J, Hannon E, Turecki G, Kaminsky Z, Mill J, Dempster EL, Murphy TM

    Attenuated Induction of the Unfolded Protein Response in Adult Human Primary Astrocytes in Response to Recurrent Low Glucose

    DOI: https://doi.org/10.3389/fendo.2021.671724
    Journal: Frontiers in Endocrinology
    Year: 2021
    Authors: Weightman-Potter PG, SJ Washer, Jeffries AR, Holley JE, Gutowski NJ, Dempster EL, Beall C

    Variation on a theme: mapping microglial heterogeneity

    DOI: https://doi.org/10.1016/j.tig.2021.09.004
    Journal: Trends in Genetics
    Year: 2021
    Authors: Washer SJ, Cowley SA, Basset AR

    Functional characterization of the schizophrenia associated gene AS3MT identifies a role in neuronal development

    DOI: https://doi.org/10.1002/ajmg.b.32905
    Journal: American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
    Year: 2022
    Authors: Washer SJ, Flynn R, Oguro-Ando A, Hannon E, Burrage J, Jeffries A, Mill J, Dempster EL

    Evaluation of nanopore sequencing for epigenetic epidemiology: a comparison with DNA methylation microarrays

    DOI: https://doi.org/10.1093/hmg/ddac112
    Journal: Human Molecular Genetics
    Year: 2022
    Authors: Flynn R, Washer S, Jeffries AR, Andrayas A, Shireby G, Kumari M, Schalkwyk LC, Mill J, Hannon E