Postdoc @Marsonlab @GladstoneInst @UCSF | PhD in Virology with @jkagan1 @harvardmed | Interest in Mechanistic Immunology, Cell Biology, Synthetic Biology
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The final version of my first postdoc paper is out today in @NatureBiotech! nature.com/articles/s41587-0…
Together with @HyuncheolJung @jccarnevale we established a virus-like particle toolkit for genetic engineering and pooled CRISPR screening in primary human myeloid cells 🧬
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Pascal Devant retweeted
Antigen discovery and TB vax friends 🧵
We set out to find more Mtb peptides presented on MHC-I. We had a strong biological prior, a high-throughput binding screen, and a very sensitive targeted MS assay.
Of 286 candidates, we detected 2.
biorxiv.org/content/10.64898…
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Pascal Devant retweeted
Thrilled to share that our work on genome-scale perturb-seq in primary human T cells is now published in Cell (cell.com/cell/fulltext/S0092…) 🎉. The original post summarized most key results ⬇️ with a few key updates:
Together with Emma Dann, we are thrilled to present a massive new Perturb-seq atlas of 22M primary CD4+ T cells, from 4 donors, across 3 timepoints – the result of a decade-long collaboration between the Marson (@MarsonLab) and Pritchard (@jkpritch) labs.
🧵👇
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Pascal Devant retweeted
Change the textbooks. Trans-splicing as a means to diversify the proteome. Many congrats to Ruaidhri Jackson and Olivia Venezia on this remarkable discovery.
nature.com/articles/s41586-0…
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Pascal Devant retweeted
🚨 NEW PUBLICATION 🚨 "Virus-like particles enable targeted gene engineering and pooled #CRISPR screening in primary human myeloid cells"
@UCSF
@jccarnevale
@NatureBiotech
go.nature.com/4gbVKJS
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Pascal Devant retweeted
Scientists at Gladstone and @UCSF developed a method to genetically edit myeloid cells, immune cells that act as the body’s first responders.
@NatureBiotech
@jccarnevale
bit.ly/3SGx5Fw
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Pascal Devant retweeted
Another major milestone for my lab - our second paper is out today in Nature Biotechnology! Co-led by @pascal_devant & @HyuncheolJung, with Alex Marson: nature.com/articles/s41587-0…
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This was a massive team effort, made possible by our many collaborators @j_eyquem Brian Shy @CrisprEh @RonZhu2015 @jkpritch @MinetoOta @WayneNgo1 @davidrliu @DoudnaJennifer Nathaniel Landau and more!
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KO of A20 drove a proinflammatory state resistant to suppressive repolarization and enhanced cytotoxicity in HER2-CAR macrophages. With TNFAIP3 surfacing as a brake on antitumor function now in both T cells and macrophages, it may be an attractive target for cell therapies.
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Our screens converged on the gene TNFAIP3, which codes for the protein A20, as a master regulator of macrophage inflammatory polarization.
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To make pooled screening possible we developed SLICeVLP, sgRNA delivery by lentivirus with Cas9 delivery by eVLPs. We used it for pooled loss-of-function screens and Perturb-seq in primary human macrophages, identifying regulators of inflammatory signaling.
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This platform supports knockout, base editing, and epigenetic silencing, and paired with AAV donor delivery it enables site-specific integration of large sequences by homology-directed repair, even in these post-mitotic cells.
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@HyuncheolJung and I adapted these VLP-based methods to deliver CRISPR ribonucleoproteins to primary human monocytes, macrophages, and dendritic cells at high efficiency while preserving both viability and innate immune responsiveness.
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When looking for alternative delivery methods for CRISPR gene editing cargos, we came across virus-like particle (VLP) that @davidrliu and @DoudnaJennifer's labs have developed recently.
nature.com/articles/s41587-0…
nature.com/articles/s41587-0…
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Primary human myeloid cells in particular have been largely inaccessible to functional genomics, hampered by cell loss and functional impairment upon nucleofection, meaning pooled screening approaches that reshaped T cell biology have not been available in macrophages and DCs.
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When I started my postdoc in the Marson lab, I was amazed by the CRISPR editing and screening technologies that the lab had established in human T cells, but this also made clear to me how far behind we were in achieving comparable feats in cells of the innate immune system.
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Pascal Devant retweeted
Virus-like particles enable targeted gene engineering and pooled CRISPR screening in primary human myeloid cells nature.com/articles/s41587-0…
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