 
            
              Dr Sam Washer
            
            @SamWasher2
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              Research Fellow at the University of Oxford; CRISPR Screens and functional genomics for Alzheimer’s Disease 🧬 Part time jazz-man/baker/climber. Views my own.
              
              Oxford
            
            
              
              Joined December 2012
            
            
           I am thrilled to announce that my first, first-author publication from my PhD journey is now finally live on bioRxiv!  https://t.co/Az8ojrOnLJ  🥳🍾👏🎉 In this work, we used iPS-microglia to create a ‘’Everything you ever wanted to know about human microglial reaction to tau…’’ 
          
            
            biorxiv.org
              The templated spread of tau aggregates in tauopathies has been attributed to neuron-to- neuron spread, but microglia have also been implicated through mouse studies. Here we examine in detail the...
            
                
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             👋 switching over to bsky, give me a follow for more microglial antics  https://t.co/PKQQnPSgWI 
          
          
                
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             We're back in the studio today, recording a podcast with @nottalexi @Josiaharvey @sj_marzi @SamWasher2 & hosted by @FHMcLean. Can you guess the topic? 
          
                
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             Wednesday cellfie: KOLF2.1S iPSC microglial + neuron co-cultures, so pretty😍What's not shown is the pain of optimizing these conditions... Hopefully these models can help us further understand the molecular basis of Alzheimer's disease🧠 #ForACure
          
          
                
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             If you are at #ADPD2024 in Lisbon come see our posters of our studies of DNA methylation meta-analyses in Lewy body disease led by @Josiaharvey and @Jenny_Imm, and spatial transcriptomics in the J20 amyloid model led by @millie_sander
          
          
                
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             Excited to see this work from my Postdoc in Andrew Bassett's lab at @sangerinstitute finally out in the world!  https://t.co/Al2v96iCV6  we found an AD-associated variant in PTK2B that actually has a causal effect on chromatin accessibility, gene expression and microglial function 
          
                
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             Microglia NLRP3 inflammasome 'DUBbed' by UCH-L1 @Zhu_L_Oxford @AndreasDamiano2 @flassen_ @ProteomOX @TaoDongGroup @theRafLab @TateScience @CmdOxford @CAMS_COI_Ox @ARUK_ODDI @KirOxford @bdi_oxford @HumanGeneticsOx @Dunn_School @NDMOxford
          
          
            
            biorxiv.org
              Activation of the NACHT, LRR family pyrin domain containing 3 (NLRP3) inflammasome complex is an essential innate immune signalling mechanism. To reveal how human NLRP3 inflammasome assembly and...
            
                
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             Come hear @MartaP4lcantara presenting on how we're mapping sceQTLs in iPSC-derived microglia to interpret neurodegeneration GWAS variants. Starting soon: 11:45am Ballroom A. A collaboration with @OpenTargets #ASHG2023
          
          
                
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             Some superb talks today around neuroinflammation in Alzheimer's Disease at #AAIC23 So don't miss out on the chance to come and chat all things iPSC microglia and CRISPR screening with me at poster 111 🧬🔬 
          
                
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             1 in 3 names are missing on the #Lionesses shirts tonight, representing the 1 in 3 of us born in the UK today who will develop dementia. Tonight’s match was dedicated to @alzheimerssoc, raising vital funds to those devastated by dementia. Donate now:  https://t.co/16pMHNcebk  👈 
          
                
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             Congratulatuons Rebecca! And thanks so much to the panel, always a pleasure to talk about my work. Thanks to the PDA organisers for a great day of science 👨🏼🔬 
           Congratulations to the winners of our postdoc symposium's prizes! Talk 1st prize: Rebecca Smith from @IvanAhelLab Talk runner up: Sam Washer from the @WilliamSiwJames group Poster 1st prize: Evangelos Mourkas (Sheppard group) Poster runner up: Yuichi Tsuchiya (Carvalho group) 
          
                
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             Excited to share that this work is now out in Scientific Reports 🥳Give it a read, download, share!  https://t.co/u97gk6s4QA 
          
           Thrilled to share our latest preprint on iPSC microglia differentiation. If you have been using the Haenseler et al 2017 protocol then you'll want to check out this update from the Cowley lab  https://t.co/GspaIa9AT6  1/n 
          
                
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            #DataScience #PhD opportunity for quantitative student looking to apply their skills to big biological datasets. Be part of the @GW4BioMedDTP @ExeterMed and @PsyEpigenetics exploring methods to computationally derive cell-type specific epigenetic profiles to understand
          
          
                
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             Position available at @ExeterMed to work with on alternative splicing and epigenetic modifications in models of Alzheimer's disease pathology. @ExeterNeuro
             https://t.co/QU7UtQ7uwp  Please RT!
          
          
                
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             This has been a huge volume of work with lots of challenges but a big thanks to everyone involved at University of Oxford (Sally/@WilliamSiwJames) and the Wellcome Sanger Institute (Yixi, Marta, Juliette, Andrew), and for @OpenTargets for funding the work! 
          
                
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             Finally, we show that the microglia cultured in ITMG show similar phagocytic capacity to our old media for Amyloid beta, 448 labelled silica beads, and a novel dead neuron traffic light assay for autophagy. Showing they retain this core function 
          
                
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             scRNAseq confirmed the qPCR data, showing that our new media (ITMG) as well as promoting survival and reproducibility, show an increased microglial identity and reduced perivascular identity compared to our original media (IGBN) using LabelTransfer from two available datasets. 
          
                
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             Geltrex performed poor so was discarded. We saw high variability across differentiations (compared ITM ADMEM below with above), however supplementation with GM-CSF promoted survival and retention without affecting the transcriptome (ITMG) 
          
                
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             IL-34 (I), TGFB1 (T), MCSF (M), GM-CSF (G) were taken forward for further characterization. We trialed 3 TC coatings as well. Media had the largest effect on gene expression with TGFB supplementation improving microglial identity and reducing perivascular macrophage identity 
          
                
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             We first found that FBS (F) supplementation resulted in fibroblast outgrowth and IL-34 (I) on it's did not support survival. We also found that CD200/CX3CL1 (C), BMe (B), and N2 (N) had no effect on the expression of a panel of known microglial markers 
          
                
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