Radek Nowak
@RPNowak
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Professor @UniBonn. Former @DanaFarber @harvardmed | Targeted Protein Degradation | Chemical and Structural Biology | @UniofOxford alumni. Tweets are my own.
Bonn, Germany
Joined November 2013
Targeted protein #degradation: from mechanisms to #clinic. New molecular mechanisms can rapidly be translated - we can learn so much from nature. Great to be able to share this piece with @jonathanMtsai Ben Ebert and Eric Fischer @fischerlab1. #TPD
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Our new lab website is live! 👉 https://t.co/91TSBWYDTk We are looking for a postdoc in #structuralbiology / #cryoEM to join our lab at the University of Bonn @UniBonn. Please share or reach out!
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Induced proximity-based therapeutic modalities https://t.co/hzBGTQEVyt
https://t.co/Y7toX848yE This new Review discusses the rapidly expanding landscape of therapeutic approaches based on inducing proximity between proteins, including targeted protein degraders and more
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Was so much fun to be part of that journey! So much for the exciting science and most importantly friendships. To the next 10! @fischerlab1
This month we celebrated a decade of the @fischerlab1 - 10 years of discovery, innovation, and collaboration! Thank you to everyone who’s been part of this journey — past and present lab members, collaborators, and supporters. Here’s to the next 10! 🧪🎉
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Excited to present our research at the Promega TPD and Induced Proximity Summit this Thursday! #TPD #UniBonn
https://t.co/BJ6Ku0uGeb
promega.foleon.com
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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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A new study in @MolecularCell by @DanaFarber’s @biomiko, Benjamin Ebert, MD, PhD, and @fischerlab1 reports a systematic screen of 9,000 zinc fingers revealing 38 new CRBN-recruited degrons. This includes targets invisible to proteomics, expanding the ZF proteome map to guide drug
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Thanks to all co-authors: @jeanniescience Simran Rastogi, Anna Goldstein, ​ Marek Nagiec, Kathrine Donovan, Jianwei Che, Moritz Hunkeler, Chi-Lin Hsu, Megha Lakshminarayan, Chelsea Shu @beckyzon @zkozicka Paul Park @jonathanMtsai @hojong_yoon @LynJonesChemBio @adamssperling
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This work was a fantastic collaboration: 🔬Structure: @jihojasonpark, @RPNowak, @ssroyburman - @fischerlab1 🧬 Functional Genomics: JessePellman, CharlesZou - Ebert lab ⚗️Chemistry: Hlib Razumkov, Qixiang Geng (Gray lab)
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A single ZF residue can switch a drug’s specificity. That’s a lever for rational molecular‑glue design.
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Chemistry rewires biology: subtle changes to glutarimide analogs reshape degron selectivity, reprogramming CRBN toward new ZF targets.
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Structure + mutagenesis reveal distinct CRBN recruitment modes—different substrates or drugs interact with different CRBN surfaces.
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CRBN is more versatile than expected: potent degraders can overcome β-hairpin mutations and still engage substrates.
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Degron profiling reveals hidden off-targets: OSR1 is not detected in proteomics experiments, yet emerges as a CRBN substrate. OSR1 plays a critical role in kidney development—highlighting potential clinical implications.
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Some ZF targets disappear in proteomics yet light up in reporter assays. Function-first discovery fills key blind spots.
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We uncovered 38 ZF degrons from 33 proteins—broadening what’s actually druggable in ZF biology.
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Our ~9k Zinc Finger Library allows profiling of thalidomide analogs’ activity using flow-based sorting screens.
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We mapped the zinc‑finger (ZF) “degrome.” High‑throughput ZF reporters + glutarimide analogs → new CRBN‑recruited degrons and design rules for degraders.
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Through functional genomics and structural biology we mapped the transcription factors degraded by CRBN molecular glues. Exciting surprises too! #CRBN #molecularglues
We mapped the zinc‑finger (ZF) “degrome.” High‑throughput ZF reporters + glutarimide analogs → new CRBN‑recruited degrons and design rules for degraders.
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🧩 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
Nature Communications - Induced proximity by molecular glues is a strategy that leverages the recruitment of proteins to facilitate their modification or degradation. Here the authors present...
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