John Tuddenham
@TuddenhamJohn
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MD/PhD Student @Columbia with Phil De Jager in the Center for Translational and Computational Neuroimmunology and @psimslab in the Department of Systems Biology
Columbia University
Joined April 2022
🧵1/9 Excited to share our latest research on human microglia! We explored microglial heterogeneity through single-cell RNA sequencing of 215,680 live human microglia from 74 donors across neurological diseases. #NeuroImmunology #Microglia @NatureNeuro
https://t.co/xVCsILDrqc
nature.com
Nature Neuroscience - Profiling >200,000 live human microglia from 74 donors across neurological diseases reveals 12 subtypes of microglia that were validated in situ. Camptothecin is also...
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Also check out our follow-ups exploring topoisomerase inhibitors across model systems ( https://t.co/NCfThxDDFm) and HDAC inhibitors as modulators of the DAM signature ( https://t.co/qcx1CrATkI) . Stay tuned for more to come! 🚀🔬 #Research #DrugDiscovery #Neurobiology #Microglia
biorxiv.org
Disease-associated microglia (DAM), initially described in mouse models of neurodegenerative diseases, have been classified into two related states; starting from a TREM2-independent DAM1 state to a...
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8/9 Shout out to my wonderful co-first authors, @HaageVc and @MarikoTaga, as well as the senior authors, @martala79, Vilas Menon, and one of my PhD mentors, Phil De Jager. Shoutout as well to my joint PhD mentor, @psimslab!
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7/9 This research underscores the importance of microglia in neurological diseases and opens up new pathways for targeted therapies. Excited to continue exploring the implications of our findings for future research and treatment strategies! 🌟 #Neuroscience #TherapeuticTargets
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6/9 Among these, camptothecin stood out! It downregulates disease-enriched signatures while upregulating a profile linked to Alzheimer's disease, offering potential therapeutic avenues. #Alzheimers #Therapeutics
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5/9 Our dataset also enables the identification and in vitrovalidation of compounds that up- or down-regulate specific microglial states. #DrugDiscovery
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4/9 Notably, we discovered that induced pluripotent stem cell models can recapitulate substantial in vivo microglial heterogeneity, paving the way for future research. #StemCells #iPSCs
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3/9 We validated these microglial subtypes using an innovative RNAscope-immunofluorescence pipeline and high-dimensional MERFISH. The integration of these techniques allows for robust subtype identification. #Methodology
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2/9 Our findings reveal a central divide in microglial profiles, highlighting subsets enriched in disease genes and associated with antigen presentation, motility, and metabolism. We also identify a spectrum of DAM-like clusters. #Neurology #Research
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Yay - Our paper is out in @NatureNeuro today: A #CRISPR i/a platform in iPSC-derived human #microglia uncovers regulators of disease states. Great collaboration with @LiGanLab, led by @KampmannLab @DraegerNina & @sydsat and @LiGanLab Cindy Huang. (1/3)
nature.com
Nature Neuroscience - Dräger et al. establish a rapid, scalable platform for iPSC-derived microglia. CRISPRi/a screens uncover roles of disease-associated genes in phagocytosis, and regulators...
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Really excited to share our newest work on identifying (and reproducing!) human microglial heterogeneity across neurological diseases. Looking forward to sharing the story with @KeystoneSymp at the incredible joint #KSNeuroImmune22 & #KSNeurodegen22 meeting!
A cross-disease human microglial framework identifies disease-enriched subsets and tool compounds for microglial polarization. https://t.co/jYfaO1WP8f
#biorxiv_neursci
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Attend in person or via livestream! Joint @KeystoneSymp joint meetings next week: #KSNeuroImmune22 & #KSNeurodegen22. Explore #neuroinflammation #microglia #Neuroimmune #CNS #Neurodegeneration & more! https://t.co/M8MB3ms1jr & https://t.co/9mwlPLNaHS
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