Shourya S Roy Burman

We expand the range of zinc finger transcription factors that can be targeted by degraders via CRBN. Once thought undruggable, our work shows how functional genomics uncovers new targets missed by proteomics and reveals rules for the structure–activity relationship of compounds.

🧩 New paper out in Nature Communications! "Unveiling the hidden interactome of CRBN molecular glues" Huge thanks to our incredible team and collaborators who made this possible! 📖 Read the full open-access article here: nature.com/articles/s4146…

Join us on April 17th for an exciting double seminar from the University of Dundee @UoDCeTPD: @CharlCrowe on "Mechanisms of degrader-targeted protein ubiquitinability" and @ales_salerno on "FerroTACs." Details: …afarbertargetedproteindegradation.org

Very excited for our next seminar this Thursday (March 20th): Martin Schwalm (@thesgconline, form. Knapp lab) will discuss UPS inhibitors and @DeanClift1 (@TRIMTECHtx) will share insights on hijacking TRIM21! 👉Join us at 12 PM EST/ 5 pm CET (‼️US/EU daylight saving mismatch‼️)

Very excited for our next seminar next week! Yuh Min Chook(@yuhminchook) at UTSW will share an intriguing allosteric mechanism of drug-induced XPO1 degradation, mediated by the CRL5-ASB8 E3 ligase complex. Join us at 12 pm EST (Feb 20th). Preprint - biorxiv.org/content/10.110…

For the first TPD webinar of 2025, we are thrilled to welcome @DennisWhom from @drughuntersite to share industry highlights in targeted protein degradation & induced proximity. 🗓️ Jan 9 | 🕛 12 PM EST Open to all, register for free at: dfci.zoom.us/webinar/regist…

Join us for the final TPD webinar of 2024 on 12/19. @FleurMFerguson & @eswang01 - "ZBTB11 Degraders Target Metabolic Vulnerabilities in K-Ras Inhibitor Resistant PDAC" Slava Ziegler - "Targeting IDO1 by monovalent degraders exploiting the native IDO1 degradation mechanism"

We are thrilled to have @georg_e_winter @CeMM_News return to the DFCI TPD webinar this Thursday! Georg will talk about how inhibitors can supercharge endogenous degradation mechanisms. Very much looking forward! 👉Join us at 12 PM EST/ 6 pm CET (hybrid format)

Very excited for our next seminar this Thursday: Derek Bartlett (formerly @pfizer, now @UNC) will share insights on PK-PD modelling for TPD and Kyle Mangano (@Amgen) will present how VIPER-TACs co-opt viral E3s. 👉Join us at 12 PM EST/ 6 pm CET (back to original schedule)!

We are happy to share our new preprint @biorxivpreprint "Unveiling the hidden interactome of CRBN molecular glues with chemoproteomics" led by @KheewoongBaek and Rebecca Metivier of @fischerlab1 biorxiv.org/content/10.110…

Extremely excited about our next in-person TPD event. If you are in Boston on September 12th - sign up and join us for a half day of science and networking! Registration link: forms.gle/a8p2ALX9n2YDWt…

@FranziskaWacht1 @DFBC_PedCare @BostonChildrens @DFCI_ChemBio @DFCI_CCBM @fischerlab1 Congrats Franzi!

Grateful for the tremendous support for my research which focuses on the development of novel treatments for hard-to-treat pediatric leukemia. Thank you all! Together, we're making the difference! @DFBC_PedCare @BostonChildrens @DFCI_ChemBio @DFCI_CCBM @fischerlab1

Amazing discovery on how some transcription factors self-polymerize to function. Opens the door for yet another ligandable way to target the function of these "undruggable" proteins. Congrats on making the cover Paul Park and @jihojasonpark!

Just in time for #HumpDay: Our study Targeting DCAF5 suppresses #SMARCB1-mutant #cancer via stabilizing SWI/SNF is online now in @Nature. Congratulations 🎉 to co-first authors Sandi-Radko-Juettner and @HongYue88665668 and all co-authors on this story! 1/ nature.com/articles/s4158…

Reminder about the seminar tomorrow - 11AM eastern time!!

Having enjoyed the paper from @davidrliu, @fischerlab1, and @ChoudharyLab in @ScienceMagazine this week, we have now posted our own, complementary, taken on a bump-and-hole approach to develop an orthogonal bumped IMiD-degron pair: biorxiv.org/content/10.110….

@moritzhunkeler Yeah, several months spent purifying different constructs in different expression systems to isolate the ZnF. Turns out the first bacterial tagged construct we had was good enough. Funny how these things work out.

When Shourya told me he couldn't cut the MBP off his ZnF, I thought oh boy that could be a problem (because of added flexibility/heterogeneity). Turns out: no problem at all --> ZnF structure without MBP, and 4 Å MBP structure from the same data set :D science.org/doi/10.1126/sc…

Thanks for your comments, Jay. To answer your question: 1) dTag uses FKBP12-F36V, which is 108 amino acids (324 bp). Unfortunately this size is too large to be directly and scarlessly installed using prime editing; we tried as part of our TwinPE studies (pubmed.ncbi.nlm.nih.gov/34887556/) but could only precisely install ~1/3 of the FKBP12 gene efficiently. 2) dTag small molecules degrade off-target ZF proteins, as shown in the attached figure from ncbi.nlm.nih.gov/pmc/articles/P… 3) The dTag system requires heterobifunctional molecules consisting of AP1867—linker—IMiD, and thus are subject to hook effects as you showed in your beautiful NCB paper. I appreciate that #2 and #3 might be addressed with dose-finding though it would be preferable to avoid the issues all together. You could install dTag or other larger degron tags with HDR though generally with lower efficiency, higher byproducts, and the consequences of making chromosomal breaks.

A new PACE-based system generates protein degradation tags that interact with an otherwise-inert small molecule to trigger the rapid breakdown of a cell’s native proteins, with molecular glue systems that can become useful new research tools. broad.io/Pace-News-0314…

And to @CancerResearch for funding this moonshot project of making potent degrons that can act as post-infusion switches in the next generation of engineered cell therapies. 6/6

Big thanks to @moritzhunkeler, @SDixonClarke, @HC2EM, @SBGrid for the structure. And @kdonovan1008, @eric_fischer, and @fischerlab1 for proteomics, biochemistry, and everything else. Glad to be part of this wonderful collaboration with @davidrliu lab and @ChoudharyLab. 5/6

We engineered a new tool to interrogate biological pathways and validate cancer dependencies! This new degron can be fused to your protein of interest at its genomic locus to degrade it within an hour using a clean compound. science.org/doi/10.1126/sc… 1/6