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

Joined July 2021
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
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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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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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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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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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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@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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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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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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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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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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Pascal Devant retweeted
Incredibly excited to share the first major paper from my lab @carnevale_lab led by postdoc Qi Liu @GladstoneInst @UCSF executing the first ever genome-wide in vivo screens for genetic modifications to enhance human T cell therapies for solid tumors. Now in @Nature: nature.com/articles/s41586-0…
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Pascal Devant retweeted
Our paper introduces membrane-impermeable caspase inhibitors that use GSDMD pores as their entry route. Because these compounds can't cross an intact membrane, they enter only cells already forming GSDMD pores — before pore density exceeds the cell's repair capacity. This confers built-in specificity: the drug acts solely on pyroptotic cells, leaving apoptosis and healthy cells untouched, addressing the off-target toxicity that has limited earlier, cell-permeable caspase inhibitors. The effect goes beyond arresting cell death. Cells already committed to pyroptosis reverse course and regain viability — a "Lazarus effect" that challenges the assumption that lytic cell death, once initiated, is irreversible. In essence, these unexpected results could create new opportunities for precisely targeting inflammatory cell death while safeguarding healthy tissue.
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