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Sam Washer

BSc. PhD.


Alzheimer's Research UK Fellow

Functional genomics and CRISPR screening in iPSC models of Alzheimer's and Neurodegenerative diseases

Research Focus

Sam is an Alzheimer's Research UK funded Research Fellow in Functional Genomics at the Centre for Medicines Discovery (CMD) and Target Discovery Institute (TDI), University of Oxford. His research is focused on combining genetics and transcriptomics with high-throughput and high-content screening in human induced pluripotent stem cell derived (hiPSC) microglia in relation to neurodegenerative disorders, with a particular focus on Alzheimer's disease.

Microglia and Alzheimer's disease

Microglia are the resident tissue macrophage of the brain and undertake numerous functions to maintain a healthy brain environment, including clearance of debris (phagocytosis), regulation of other brain cell types (neurons/astrocytes), release of signaling chemicals (cytokines), synaptic pruning, regulating inflammation, and surveillance. From genetic studies of people with and without AD, we now know that mutations in microglia specific genes are enriched in people with AD. The next step is to link these genetic mutations to their functional consequences to understand their role in the pathophysiology of the disease. We can further utilize the genetic and functional evidence to direct and inform the creation of novel drugs to help people living with AD and other dementias. 

To do this he has several aims:

  1. Improve current methods of iPSC microglia generation
  2. Evaluate which phenotypes are influenced by genetic drivers of Alzheimer's disease in iPSC microglia
  3. Explore how transcriptional variation drives diverse microglia cellular phenotypes
  4. Develop novel functional (epi)genomic techniques 

Prior to joining the CMD, Sam completed his BSc in Medical Science from the University of Exeter in 2016, with a focus on genomics, bioinformatics, and immunology. Following this he obtained his PhD in Medical Studies from the University of Exeter in 2019, under the supervision of Dr Emma Dempster and Prof. Jonathan Mill his thesis explored novel methods of functional genomics and epigenomics in validating (epi)genetic risk loci in schizophrenia. Sam then undertook further postdoctoral training at the Wellcome Sanger Institute, Cambridge, in the lab of Dr Andrew Bassett, exploring the role of microglia in neuroinflammation. During this position, he was seconded to the University of Oxford and worked with Prof. Sally Cowley, Sir William Dunn School of Pathology, University of Oxford, on developing the iPSC microglia model and a novel method for measuring phagocytosis, then with Prof. Daniel Ebner at the CMD, to undertake a CRISPR screen for neuronal phagocytosis. 

For all studentship enquiries, please contact - sam.washer@cmd.ox.ac.uk

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