Pascal Devant

Postdoc @Marsonlab @GladstoneInst @UCSF | PhD in Virology with @jkagan1 @harvardmed | Interest in Mechanistic Immunology, Cell Biology, Synthetic Biology

[Pascal Devant @pascal_devant]

The final version of my first postdoc paper is out today in @NatureBiotech! https://t.co/8Boy5Tqb5g
Together with @HyuncheolJung @jccarnevale we established a virus-like particle toolkit for genetic engineering and pooled CRISPR screening in primary human myeloid cells 🧬

[Bryson Lab @TheBrysonLab]

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.

https://t.co/XfEeoMLWMD

[Ronghui (Ron) Zhu @RonZhu2015]

Thrilled to share that our work on genome-scale perturb-seq in primary human T cells is now published in Cell (https://t.co/Cb2qom8RLB) 🎉. The original post summarized most key results ⬇️ with a few key updates:

[Jonathan Kagan @jkagan1]

Change the textbooks. Trans-splicing as a means to diversify the proteome. Many congrats to Ruaidhri Jackson and Olivia Venezia on this remarkable discovery.
https://t.co/gER6ME71AH

[Gladstone Institutes @GladstoneInst]

🚨 NEW PUBLICATION 🚨 "Virus-like particles enable targeted gene engineering and pooled #CRISPR screening in primary human myeloid cells"

@UCSF
@jccarnevale
@NatureBiotech

https://t.co/9yJlusI0wV

[Gladstone Institutes @GladstoneInst]

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

https://t.co/4ET2Uaj0vg

[Pascal Devant @pascal_devant]

@jkagan1 @NatureBiotech @HyuncheolJung @jccarnevale Thanks Jon!

[Pascal Devant @pascal_devant]

The final version of my first postdoc paper is out today in @NatureBiotech! https://t.co/8Boy5Tqb5g
Together with @HyuncheolJung @jccarnevale we established a virus-like particle toolkit for genetic engineering and pooled CRISPR screening in primary human myeloid cells 🧬

[Pascal Devant @pascal_devant]

@Lo_Zanzi @NatureBiotech @HyuncheolJung @jccarnevale Thanks Ivan!

[Pascal Devant @pascal_devant]

@j_eyquem @CrisprEh @RonZhu2015 @jkpritch @MinetoOta @WayneNgo1 @davidrliu @DoudnaJennifer @UCSF @GladstoneInst @UCBerkeley @broadinstitute @nyuniversity @Harvard @MIT

[Pascal Devant @pascal_devant]

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 @pascal_devant]

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!

[Julia Carnevale @jccarnevale]

Another major milestone for my lab - our second paper is out today in Nature Biotechnology! Co-led by @pascal_devant & @HyuncheolJung, with Alex Marson: https://t.co/5clz6kFPgt

[Pascal Devant @pascal_devant]

Our screens converged on the gene TNFAIP3, which codes for the protein A20, as a master regulator of macrophage inflammatory polarization.

[Pascal Devant @pascal_devant]

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.

[Pascal Devant @pascal_devant]

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.

[Pascal Devant @pascal_devant]

@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.

[Pascal Devant @pascal_devant]

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.
https://t.co/wAUiKbLH0Q
https://t.co/mWVVco7HZw

[Pascal Devant @pascal_devant]

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.

[Pascal Devant @pascal_devant]

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.

[Nature Biotechnology @NatureBiotech]

Virus-like particles enable targeted gene engineering and pooled CRISPR screening in primary human myeloid cells https://t.co/iOmLkU6DaX