Pascal Devant @pascal_devant
Postdoc @Marsonlab @GladstoneInst @UCSF | PhD in Virology with @jkagan1 @harvardmed | Interest in Mechanistic Immunology, Cell Biology, Synthetic Biology Joined July 2021-
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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/…) 🎉. 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/s4158…
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
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
@jkagan1 @NatureBiotech @HyuncheolJung @jccarnevale Thanks Jon!
The final version of my first postdoc paper is out today in @NatureBiotech! nature.com/articles/s4158… Together with @HyuncheolJung @jccarnevale we established a virus-like particle toolkit for genetic engineering and pooled CRISPR screening in primary human myeloid cells 🧬
@Lo_Zanzi @NatureBiotech @HyuncheolJung @jccarnevale Thanks Ivan!
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!
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.
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/s4158…
Our screens converged on the gene TNFAIP3, which codes for the protein A20, as a master regulator of macrophage inflammatory polarization.
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.
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.
@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.
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/s4158… nature.com/articles/s4158…
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.
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.
Pascal Devant retweeted
Virus-like particles enable targeted gene engineering and pooled CRISPR screening in primary human myeloid cells nature.com/articles/s4158…
Pascal Devant retweeted
@jccarnevale @carnevale_lab is on a tear! now led by @pascal_devant and @HyuncheolJung, with Alex Marson, out today in @NatureBiotech: Virus-like particles enable targeted gene engineering and pooled CRISPR screening in primary human myeloid cells nature.com/articles/s4158…
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