Steven Cheng

Steven Cheng

@scheng23.bsky.social

Chemistry & Chemical Biology PhD Candidate @Harvard woolab.org | Chemical Engineering @Stanford Alumnus | Small molecules 💊, PTMs (esp O-GlcNAc 🟦), RNA splicing 🧬

534 followers1.2K following36 posts

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Steven Cheng
@scheng23.bsky.social

Excited to share "Opportunities for Therapeutic Modulation of O-GlcNAc" @acspublications.bsky.social Chemical Reviews with Alison Mody in the Woo lab, our contribution to an upcoming special issue "Drugging the Undruggable". (1/6) pubs.acs.org/doi/10.1021/... #glycotime

pubs.acs.orgOpportunities for Therapeutic Modulation of O-GlcNAcO-Linked β-N-acetylglucosamine (O-GlcNAc) is an essential, dynamic monosaccharide post-translational modification (PTM) found on serine and threonine residues of thousands of nucleocytoplasmic protein...

Steven Cheng reposted

Nature Reviews Molecular Cell Biology
@natrevmcb.nature.com

ICYMI: New Online! Probing the effects of protein glycosylation on transcription with induced-proximity tools

dlvr.itProbing the effects of protein glycosylation on transcription with induced-proximity toolsNature Reviews Molecular Cell Biology, Published online: 19 February 2026; doi:10.1038/s41580-026-00955-3In this Tools of the Trade article, Alison Mody (Woo lab) discusses a proximity-induced platform for targeted O-GlcNAcylation of proteins of interest, enabling researchers to measure the effect of O-GlcNAcylation on protein function.

Steven Cheng reposted

The Woo Lab
@thewoolab.bsky.social

Let us take you to the land of sweets with our latest work in @CellChemBiol ! Excited to share this proximity-induced target O-GlcNAc approach, where we uncover transcriptional effects of O-GlcNAc. Congrats to Alison and Dan! 🟦🍭🍬🎵❄️https://sciencedirect.com/science/article/pii/S2451945625003538

Steven Cheng reposted

The Woo Lab
@thewoolab.bsky.social

Roses are red, GlcNAc is blue, sugar is sweet, and we want YOU to read our latest in @natcomms.nature.com — where we identify small-molecules that disrupt OGlcNAc homeostasis via RNA splicing. Congrats Steven (@scheng23.bsky.social) and all the authors! 🟦🍭❤️ www.nature.com/articles/s41...

nature.comSmall molecule splicing modulators that disrupt O-GlcNAc homeostasis - Nature CommunicationsAuthors report drug repurposing screens against O-GlcNAc cycling enzymes, finding kinase inhibitors that act as splicing modulators to disrupt O-GlcNAc homeostasis and downregulate OGT and OGA. These ...
Steven Cheng
@scheng23.bsky.social

www.cell.com/cell/abstrac... "Here, we confirm profound diet-PI3K anticancer synergy but show that it is, surprisingly, unrelated to diet macronutrient composition. Instead, the diet-PI3K interaction involves microbiome metabolism of ingested phytochemicals."

cell.comMicrobiome metabolism of dietary phytochemicals controls the anticancer activity of PI3K inhibitorsDiet can impact anticancer drug activity. A classic example in rodents is a ketogenic diet enhancing PI3K inhibitor activity. Here, we show that phytochemicals and their microbiome derivatives, rather...
Steven Cheng
@scheng23.bsky.social

www.nature.com/articles/s41... "Lipoamide partitions into stress granules in cells, prevents formation of stress granules and dissolves existing stress granules, allowing us to identify a pathway that allows stress granules to sense the oxidative state of the cell."

nature.comSmall-molecule dissolution of stress granules by redox modulation benefits ALS models - Nature Chemical BiologyUechi et al. found that a small-molecule lipoamide dissolves stress granules (SGs) by targeting SFPQ, a redox-sensitive disordered SG protein, alleviating pathological phenotypes caused by amyotrophic...
Steven Cheng
@scheng23.bsky.social

Broad Target Screening Reveals Abundance of FKBP12-Based Molecular Glues in Focused Libraries pubs.acs.org/doi/10.1021/... "Our results demonstrate that molecular glues are more common than previously thought and that they can be identified by repurposing existing focused libraries."

pubs.acs.orgBroad Target Screening Reveals Abundance of FKBP12-Based Molecular Glues in Focused LibrariesCompetitive (nondegradative) molecular glues represent a promising drug modality that remains underexplored primarily due to the lack of adequate hit identification approaches. In this study, we screened our historically grown FKBP-focused library containing >1000 drug-like molecules to identify FKBP-assisted molecular glues targeting a diverse panel of 57 proteins. In addition to establishing a robust and generalizable screening approach, we discovered three novel FKBP-dependent molecular glues targeting PTPRN, BRD4BD2, and STAT4. Our results demonstrate that molecular glues are more common than previously thought and that they can be identified by repurposing existing focused libraries. An optimized, highly cooperative FKBP12-BRD4BD2 glue demonstrated the involvement of the BD2 pocket and exhibited selectivity over the closely related BD1 domain. Our results underscore the value of FKBP12-assisted molecular glues to target challenging proteins with the potential for high selectivity.
Steven Cheng
@scheng23.bsky.social

Very interesting screening approach leveraging different technologies including DELs, photocleavable linkers, microfluidics, RNA-seq to discover new bioactive VHL molecular glues

Ryan Potts - real@pottslab.bsky.social

🚨 Rational discovery of VHL molecular glues. New Preprint from @amgen.bsky.social Induced Proximity group led by postdoc Jonathan Bushman reports the discovery of a VHL molecular glue degrader of GEMIN3 by Picowell RNA-seq. Read on for details. 🧵1/8 www.biorxiv.org/content/10.1...

biorxiv.orgDiscovery of a VHL molecular glue degrader of GEMIN3 by Picowell RNA-seqTargeted protein degradation (TPD) is an emerging therapeutic modality in which small molecules are used to recruit targets to the natural protein degradation machinery of the cell. Molecular glue deg...

Steven Cheng reposted

Ryan Potts - real
@pottslab.bsky.social

🚨 Rational discovery of VHL molecular glues. New Preprint from @amgen.bsky.social Induced Proximity group led by postdoc Jonathan Bushman reports the discovery of a VHL molecular glue degrader of GEMIN3 by Picowell RNA-seq. Read on for details. 🧵1/8 www.biorxiv.org/content/10.1...

biorxiv.orgDiscovery of a VHL molecular glue degrader of GEMIN3 by Picowell RNA-seqTargeted protein degradation (TPD) is an emerging therapeutic modality in which small molecules are used to recruit targets to the natural protein degradation machinery of the cell. Molecular glue deg...
Steven Cheng
@scheng23.bsky.social

www.nature.com/articles/s41... Neat story of hit validation To further validate the compound in well H20, we purchased.. from two commercial vendors.. neither inhibited.. LC–MS revealed that the H20 compound was pure, with a mass of 555.55 Da instead of the expected mass of 382.25 Da

nature.comMolecular glues that inhibit deubiquitylase activity and inflammatory signaling - Nature Structural & Molecular BiologyThe BRCC36 isopeptidase complex (BRISC) is a deubiquitylase that stabilizes interferon receptors, driving inflammation. We discovered ‘BRISC molecular glue’ inhibitors (BLUEs) that selectively inactiv...
Steven Cheng
@scheng23.bsky.social

www.biorxiv.org/content/10.1... "We target homomeric proteins with PINCHs (Polymerization Inducing Chimeras) - bifunctional molecules composed of two linked ligands that act as bridges between homomers and trigger their supramolecular assembly into insoluble polymers."

biorxiv.orgA pharmacological modality to sequester homomeric proteinsMolecules that can perturb protein-protein interactions have an immense impact on chemical biology and therapeutics. However, such compounds typically rely on accessory proteins to function, such as E...
Steven Cheng
@scheng23.bsky.social

www.cell.com/cell/abstrac... Lysine vitcylation is a vitamin C-derived protein modification that enhances STAT1-mediated immune response “Here, we report that vitC directly modifies lysine residues to form “vitcyl-lysine”—a process termed vitcylation.”

cell.comLysine vitcylation is a vitamin C-derived protein modification that enhances STAT1-mediated immune responseVitamin C directly modifies lysine residues through vitcylation, regulating STAT1 signaling and enhancing anti-tumor immune responses by preventing STAT1 dephosphorylation.
Steven Cheng
@scheng23.bsky.social

www.nature.com/articles/s41... "We are what we eat," said the study's co-senior author Angelo D'Alessandro, Ph.D. "What we eat changes the composition of us and when immune cells eat bacteria the same thing happens to them."

nature.comMacrophages recycle phagocytosed bacteria to fuel immunometabolic responses - NaturePhagocytosed bacteria can serve as an alternative nutrient source for macrophages, influencing their metabolic and immune responses through the recycling of microbial components, with the process regu...
Steven Cheng
@scheng23.bsky.social

www.researchsquare.com/article/rs-4... A clinical drug candidate that triggers non-apoptotic cancer cell death "[t]his lethal mechanism is distinct from ferroptosis, necroptosis and pyroptosis and requires the lipid metabolic enzyme trans-2,3-enoyl-CoA reductase (TECR)"

researchsquare.comA clinical drug candidate that triggers non-apoptotic cancer cell deathSmall molecules that induce non-apoptotic cell death are of fundamental mechanistic interest and may be useful to treat certain cancers. Here, we report that tegavivint, a drug candidate undergoing hu...
Steven Cheng
@scheng23.bsky.social

Return to Flatland "Fifteen years ago, an analysis of drug molecules ... suggested that increased three-dimensional character was a marker of greater success. Now, we perform a similar analysis ... to see if the trends observed then still hold today" www.nature.com/articles/s41...

nature.comReturn to Flatland - Nature Reviews ChemistryFifteen years ago, an analysis of drug molecules moving through the stages of clinical development suggested that increased three-dimensional character was a marker of greater success. Now, we perform...

Steven Cheng reposted

Jakob Farnung
@jakobfarnung.bsky.social

🎉Super excited to share our story on how the substrate receptor FBXO31 functions as a quality control factor by recognizing amides. This has been an amazing collaboration between Bode lab and @jcornlab.bsky.social. Special shutout goes to @matthiasmuhar.bsky.social www.nature.com/articles/s41...

nature.comC-terminal amides mark proteins for degradation via SCF–FBXO31 - NatureSCF–FBXO31 scans proteins for C-terminal amidation and marks them for subsequent proteasomal degradation.
Steven Cheng
@scheng23.bsky.social

Chemoproteomic Profiling of Clickable Fumarate Probes for Target Identification and Mechanism of Action Studies pubs.acs.org/doi/10.1021/... from Biogen

pubs.acs.orgChemoproteomic Profiling of Clickable Fumarate Probes for Target Identification and Mechanism of Action StudiesDimethyl fumarate (DMF) is an established oral therapy for multiple sclerosis worldwide. Although the clinical efficacy of these fumarate esters has been extensively investigated, the mode of action and pharmacokinetics of fumarates have not been fully elucidated due to their broad-spectrum reactivity and complex metabolism in vivo. To better understand the mechanism of action of DMF and its active metabolite, monomethyl fumarate (MMF), we designed and utilized clickable probes to visualize and enrich probe-modified proteins. We further perform quantitative chemoproteomics analysis for proteome-wide target identification and validate several unique and shared targets of DMF and MMF, which provide insight into the reactivity, selectivity, and target engagement of fumarates.

Steven Cheng reposted

Jeremy Baskin
@jeremybaskin.bsky.social

Our latest story: a protein-protein interaction between an E3 ubiquitin ligase and an autophagy adaptor affects liquid-liquid phase separation and sequestration of a key mediator of antioxidant signaling — but not via ubiquitination! Bravo to Lin Luan and Xiaofu Cao! doi.org/10.1101/2025...

Steven Cheng reposted

Dr. Tom Frieden
@drtomfrieden.bsky.social

CDC's Morbidity and Mortality Weekly Report (MMWR) has provided real-time data and analysis about disease outbreaks and emerging health threats without a break every week since 1960. Until today.

Steven Cheng
@scheng23.bsky.social

"On a molecular level, our structural studies reveal that interdictors bind in a linkerless heterobifunctional manner to both the rRNA and the nascent peptide chain ... much the way a PROTAC can be modularly designed and constructed"

bioRxivpreprint@biorxivpreprint.bsky.social

Context-dependent translation inhibition as a novel oncology therapeutic modality https://www.biorxiv.org/content/10.1101/2025.01.09.632223v1

Steven Cheng
@scheng23.bsky.social

Engineering covalent small molecule–RNA complexes in living cells www.nature.com/articles/s41... "Our findings raise expectations for the development of covalent RNA drugs and contribute to the evolving field of RNA-based therapeutics."

nature.comEngineering covalent small molecule–RNA complexes in living cells - Nature Chemical BiologySmall-molecule ligands have been developed that covalently attach to their cognate RNA aptamers in vitro and in living cells. This strategy opens up new avenues for RNA imaging applications (for examp...

Steven Cheng reposted

Martin Schwalm
@martinschwalm.bsky.social

Interested in #TPD? This might be for you. What concentrations of UPS inhibitors are safe to use to prove your proteasome dependent degradation mechanism? #PROTAC #TPD #degradation #Science #drugdiscovery pubs.acs.org/doi/10.1021/...

pubs.acs.orgFunctional Characterization of Pathway Inhibitors for the Ubiquitin-Proteasome System (UPS) as Tool Compounds for CRBN and VHL-Mediated Targeted Protein DegradationSmall molecule degraders such as PROteolysis TArgeting Chimeras (PROTACs) and molecular glues are new modalities for drug development and important tools for target validation. When appropriately opti...

Steven Cheng reposted

Matthews Group
@megamatthewslab.bsky.social

1/14 Our latest study just out on BioRxiv [https://www.biorxiv.org/content/10.1101/2024.12.19.629450] has unusual personal significance for me. It connects two apparently unrelated diseases – (pre)eclampsia and glioblastoma – that have both impacted my family.

bioRxivpreprint@biorxivpreprint.bsky.social

Hydralazine inhibits cysteamine dioxygenase to treat preeclampsia and senesce glioblastoma https://www.biorxiv.org/content/10.1101/2024.12.19.629450v1

Steven Cheng reposted

Mark Dawson
@mafdawson.bsky.social

Why can a human tolerate a drug that globally inhibits transcription? Why do transcription inhibitors not cure cancer? Our first paper of 2025 may help explain (some) of this! So incredibly proud of @tobiaswilliams.bsky.social & Ewa Michalak who led the work! www.cell.com/molecular-ce...

cell.commRNA export factors store nascent transcripts within nuclear speckles as an adaptive response to transient global inhibition of transcriptionTranscription inhibitors also disrupt nuclear export. Here, Williams et al. reveal that mRNA export factors sense transcription inhibition and adapt by storing mature export-competent mRNA in nuclear speckles. This enables rapid release when transcription resumes and ensures retention of cellular identity and viability during a transient global transcription insult.

Steven Cheng reposted

Adam Gilbert
@adammgilbert65.bsky.social

Using FKBP12 DELs to discover FKBP12 glues www.cell.com/cell-chemica...

cell.comDevelopment of an FKBP12-recruiting chemical-induced proximity DNA-encoded library and its application to discover an autophagy potentiatorTan et al. designed a DNA-encoded library, comprising compact and diverse linkers, that recruits FKBP12 to any protein of interest to enable efficient discovery of non-degrader proximity inducers. The screen uncovered a compound that stabilized and reversed functional defects of the ATG16L1 T300A IBD risk variant in an FKBP12-independent manner.

Steven Cheng reposted

Michael
@schlierflab.bsky.social

It's celebration time: our first contribution to a better understanding of RNA structure and dynamics in biomolecular condensates together with Alberti lab - cool data from in vitro to in condenso to in vivo take a look 👇 @cmcb-tud.bsky.social @tudresden.bsky.social www.cell.com/molecular-ce...

cell.comG3BP-driven RNP granules promote inhibitory RNA-RNA interactions resolved by DDX3X to regulate mRNA translatabilityTrussina et al. demonstrate that the storage of mRNA molecules inside G3BP1-driven RNP granules facilitates the formation of RNA-RNA interactions, preventing the mRNA from being translated. The DEAD-box helicase DDX3X facilitates RNP granule dissolution by attenuating these inhibitory RNA-RNA interactions to aid restart of mRNA translation.

Steven Cheng reposted

Matt Hall
@cispt2.bsky.social

We don't talk enough about the biochemistry of Rudolph's nose. I assume it involves a bioluminescent enzyme, and a fluorescent protein that red-shifts the light?

Steven Cheng
@scheng23.bsky.social

Parallel Proteomic and Transcriptomic Microenvironment Mapping (μMap) of Nuclear Condensates in Living Cells From MacMillan lab pubs.acs.org/doi/10.1021/...

pubs.acs.orgParallel Proteomic and Transcriptomic Microenvironment Mapping (μMap) of Nuclear Condensates in Living CellsCellular activity is spatially organized across different organelles. While several structures are well-characterized, many organelles have unknown roles. Profiling biomolecular composition is key to ...
Steven Cheng
@scheng23.bsky.social

Covalent Proximity Inducers @acspublications.bsky.social Chem Rev by Nir London Clever graphical abstract 🎨 pubs.acs.org/doi/10.1021/...

pubs.acs.orgCovalent Proximity InducersMolecules that are able to induce proximity between two proteins are finding ever increasing applications in chemical biology and drug discovery. The ability to introduce an electrophile and make such proximity inducers covalent can offer improved properties such as selectivity, potency, duration of action, and reduced molecular size. This concept has been heavily explored in the context of targeted degradation in particular for bivalent molecules, but recently, additional applications are reported in other contexts, as well as for monovalent molecular glues. This is a comprehensive review of reported covalent proximity inducers, aiming to identify common trends and current gaps in their discovery and application.

Steven Cheng reposted

Nature
@nature.com

We've just joined Bluesky 🎉 Follow us for research, news, comment and opinion from Nature journal 🧪

Steven Cheng reposted

Helen Branswell 🇨🇦
@helenbranswell.bsky.social

#CDC has confirmed an #H5N1 #birdflu case in Louisiana, in a person believed to have been infected through contact with infected birds in a backyard flock. This person is seriously ill, the first such case recorded in the US. Similarities to the recent BC case. www.statnews.com/2024/12/18/h...

statnews.comCDC confirms first known severe case of H5N1 bird flu in the U.S.The U.S. has confirmed its first known severe human infection of H5N1 bird flu, in a person in Louisiana.

Steven Cheng reposted

Kai Kupferschmidt
@kakape.bsky.social

CDC just confirmed the first severe case of #H5N1 in the US in a patient in Louisiana. This virus seems to be the same genotype D1.1 that is spreading in birds at the moment (so not the cattle genotype B3.13) that severely sickened the teenager in Canada. #IDsky 🧪