iiinova — where your digital self keeps evolving

Reposted by Steven Corsello

Steven Banik @stevenbanik.bsky.social · 01/09/2026

Excited our ratiometric transcriptional activation (RTA) work led by postdoc Dr. Melissa Gray is out online today in Cell @cp-cell.bsky.social! Measurements determine what we can discover in biology; we use RTA to turn protein abundance changes into amplified signals in live cells.

cell.com

Ratiometric transcriptional activation by protein degradation

By tethering a protein of interest to anti-CRISPR, protein degradation is transformed into amplified and programmable transcriptional outputs via Cas-based transcription factors, with sensitivity to p...

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Steven Corsello @corsello.bsky.social · 27/05/2026

Study was led by Stephen Hinshaw, Linjie Yuan, and Md Abdullah Al Noman. Grateful for our collaborators and generous support from @damonrunyon.org @themarkfdn.bsky.social @stanford-cancer.bsky.social @stanford-chemh.bsky.social @stanforddeptmed.bsky.social @stanfordmedicine.bsky.social

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Steven Corsello @corsello.bsky.social · 27/05/2026

Mutation of key interface residues reduced TRIM21-NUP98 binding in vitro and in cells. This work has important implications for TRIM21 molecular glue development and potential new TRIM21 reprogramming opportunities.

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Steven Corsello @corsello.bsky.social · 27/05/2026

Our study shows how extensive protein-protein interactions explain the potency and surprising chemical diversity of reported TRIM21 molecular glues. We applied these structural insights to design an optimized compound and describe its structure.

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Steven Corsello @corsello.bsky.social · 27/05/2026

Excited to share our latest work, online today at Cell Chemical Biology, in which we determine the structure of the TRIM21-NPC molecular glue ternary complex to establish the molecular basis for nuclear pore destruction by an E3 ligase: doi.org/10.1016/j.ch...

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Reposted by Steven Corsello

Carolyn Bertozzi @carolynbertozzi.bskyverified.social · 21/03/2026

Great piece on @corsello.bsky.social and coworkers’ exciting new discovery @stanfordmedicine.bsky.social

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Reposted by Steven Corsello

Pauline Funchain @funchainmd.bsky.social · 15/09/2025

Great 💎s on GI cancers at #CCRTP25 @stanford-cancer.bsky.social @corsello.bsky.social -drug discovery w better yield from unexpected hits, then subsequently modified -negative results so important to publish -environmental factors like weight most likely culprits of young onset colon cancer

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Steven Corsello @corsello.bsky.social · 02/09/2025

We are also recruiting a new postdoc. If you are excited to work at the interface of functional genomics and chemical biology, please contact me to learn more! 18/18

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Steven Corsello @corsello.bsky.social · 02/09/2025

Many more details in the paper linked above. We are grateful for support from: @damonrunyon.org theNCI @stanford-cancer.bsky.social @stanfordmedicine.bsky.social @stanford-chemh.bsky.social and generous donors. 16/18

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Steven Corsello @corsello.bsky.social · 02/09/2025

TRIM21 molecular glues are emerging as an exciting research area, and our findings are complemented by excellent recent work from Ting Han, Drew Adams, and Dengfeng Dou as well as foundational work from Leo James. 15/18

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Steven Corsello @corsello.bsky.social · 02/09/2025

Most encouragingly, we observed robust TRIM21 molecular glue activity against pancreatic cancer xenografts and patient-derived PDAC organoid models. 14/18

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Steven Corsello @corsello.bsky.social · 02/09/2025

How does blocking the nuclear pore trigger apoptosis? One factor is that cancer cells are addicted to a constant stream of short-lived pro-survival mRNAs. Starving the cell of key survival signals results in rapid cell death. 13/18

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Steven Corsello @corsello.bsky.social · 02/09/2025

Why is this so effective against cancer? Prior work shows that when the nuclear pore is disrupted, cancer cells tend to die via apoptosis, while normal cells can recover. This suggests a potential therapeutic window supported by our findings with immortalized cells. 12/18

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Steven Corsello @corsello.bsky.social · 02/09/2025

We then confirmed the crucial link. Using multiple assays (NanoBiT in cells, TR-FRET in vitro), we demonstrated that the compound induces physical proximity between TRIM21 and NUP98. 11/18

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Steven Corsello @corsello.bsky.social · 02/09/2025

We went back to our original CRISPR KO screen and realized that a single guide (out of 4) against NUP98 conferred strong resistance to drug activity. This was missed at the gene summary level! The active guide uniquely targeted the NUP98 autoproteolytic domain (APD). 10/18

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Steven Corsello @corsello.bsky.social · 02/09/2025

TRIM21 is a ubiquitin ligase that labels other proteins for destruction. To identify its substrates, we performed extensive proteomic profiling and proximity labeling which demonstrated degradation of nuclear pore complex proteins. 9/18

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Steven Corsello @corsello.bsky.social · 02/09/2025

With TRIM21 as our likely molecular target, we performed a tiled base editing screen, which helped map the compound binding site to the PRYPSRY domain. Direct compound binding to recombinant TRIM21 PRYSPRY was confirmed via SPR and crystallography. 8/18

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Steven Corsello @corsello.bsky.social · 02/09/2025

In a fantastic collaboration with Nathanael Gray's lab, we developed new derivatives that were >10-fold more potent, while still being highly selective and completely dependent on TRIM21 for their activity. 7/18

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Steven Corsello @corsello.bsky.social · 02/09/2025

Next, we conducted genome-scale CRISPR KO and activation modifier screens yielding TRIM21 and IRF genes as the top functional mediators of drug response across the entire genome. 6/18

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Steven Corsello @corsello.bsky.social · 02/09/2025

The compound was re-tested in full dose-response across ~900 cell lines, yielding TRIM21 mRNA expression as the top predictive biomarker. Activity was also enriched against pancreatic and head & neck cancers. 5/18

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Steven Corsello @corsello.bsky.social · 02/09/2025

Our story begins with cell line viability profiling via the PRISM Drug Repurposing Project @CancerDepMap. We found that a former clinical drug candidate, an erastin derivative (PRLX-93936), showed highly selective anticancer activity. 4/18

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Steven Corsello @corsello.bsky.social · 02/09/2025

In work led by Linjie Yuan, Wenzhi Ji, and Brendan Dwyer, we employed large-scale phenotypic profiling, genetic modifier screens, and proteomics to discover that a prior clinical-stage drug acts as a TRIM21 molecular glue to degrade the nuclear pore complex. 3/18

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Steven Corsello @corsello.bsky.social · 02/09/2025

Excited to share our discovery of potent TRIM21 molecular glues with anticancer activity, online today @CD_AACR: "Defining the antitumor mechanism of action of a clinical-stage compound as a selective degrader of the nuclear pore complex". 1/18

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Reposted by Steven Corsello

Pauline Funchain @funchainmd.bsky.social · 09/03/2025

Good morning Monterey 🌞 Nothing like multidisciplinary discussion of GI cancers to kick off another sunny morning next to the Pacific with Lipika Goyal and Pam Basto @stanford-cancer.bsky.social reviewing 8(!!) new approvals for GI cancers 🌊 Great meeting @ ANCO branch of @ascocancer.bsky.social 🤓

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Reposted by Steven Corsello

Michael Fischbach @mfgrp.bsky.social · 11/12/2024

Today we report that an engineered skin bacterium, swabbed gently on the head of a mouse, can unleash a potent antibody response against a pathogen. Could lead to topical vaccines that are applied in a cream. @djenetbousbaine.bsky.social led the charge... @natureportfolio.bsky.social 1/55

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Reposted by Steven Corsello

Carolyn Bertozzi @carolynbertozzi.bskyverified.social · 04/12/2024

@pollyfordyce.bsky.social @stanford-chemh.bsky.social is officially a household name. That is some real impact!

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Steven Corsello @corsello.bsky.social · 25/11/2024

Stanford Hematology has launched a physician scientist search! Research program can be lab-based and/or translational. facultypositions.stanford.edu/en-us/job/49...

facultypositions.stanford.edu

Stanford | Faculty Positions: Details - Hematology Physician Scientist

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Steven Corsello @corsello.bsky.social · 24/11/2024

Hi! We work on new therapies.

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Steven Corsello @corsello.bsky.social · 10/11/2024

Checking out the science community on Bluesky!

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