Steven Cheng
Chemistry & Chemical Biology PhD Candidate @Harvard woolab.org |
Chemical Engineering @Stanford Alumnus |
Small molecules 💊, PTMs (esp O-GlcNAc 🟦), RNA splicing 🧬
- 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."
- www.nejm.org/doi/full/10.... "In this study, we describe a personalized base-editing therapy wholly developed in the 6-month span after a patient’s birth."
- 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."
- 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."
- Reposted by Steven ChengExcited to share Benson’s and Maria’s work in collab w/Kostas Tzelepis: we found the nucleolar protein NPM1 is a marker of AML and can be targeted therapeutically connecting ‘cell surface RNA biology’ to cancer biology @natbiotech.nature.com www.nature.com/articles/s41...
- Therapeutic potential of allosteric HECT E3 ligase inhibition www.cell.com/cell/fulltex... "we discover inhibitors that bind a cryptic cavity distant from the catalytic cysteine" ... "these inhibitors restrict an essential catalytic motion by extending an α helix over a conserved glycine hinge"
- Very interesting screening approach leveraging different technologies including DELs, photocleavable linkers, microfluidics, RNA-seq to discover new bioactive VHL molecular glues
- 🚨 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...
- Reposted by Steven Cheng🚨 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...
- www.nature.com/articles/s41... www.nature.com/articles/d41... A polyene macrolide targeting phospholipids in the fungal cell membrane New antifungal breaks the mould "Mandimycin is an antifungal molecule that acts by specifically targeting phospholipids"
- Reposted by Steven ChengSmall-molecule allosteric activator of ubiquitin-specific protease 7 (USP7) biorxiv.org/content/10.1101/202…
- 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
- 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."
- 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.”
- 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."
- 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)"
- Reposted by Steven Cheng🚨 New paper alert! 🚨 Check out our latest work on HypoxyStat, a small-molecule therapy that increases oxygen-hemoglobin affinity and provides a practical form of hypoxia therapy. A great collaboration with Maze Therapeutics 🔗 Paper: doi.org/10.1016/j.ce... @cp-cell.bsky.social
- Reposted by Steven ChengNow online in Cancer Discovery: Restoration of the Tumor Suppressor Function of Y220C-Mutant #p53 by Rezatapopt, a Small Molecule Reactivator - by @PuzioKuter, Lizhong Xu, Masha Poyurovsky, and colleagues doi.org/10.1158/2159...
- Reposted by Steven ChengToday in @nature.com we share our back-to-back stories with Ning Zheng’s lab revealing chemical-genetic convergence between a molecular glue degrader & E3 ligase cancer mutations. 1/5
- 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...
- Modulation of Protein–Protein Interactions with Molecular Glues in a Synthetic Condensate Platform pubs.acs.org/doi/10.1021/...
- Reposted by Steven ChengVertex wins FDA approval for non-opioid pain drug, setting stage for closely watched rollout www.statnews.com/2025/01/30/v... via @jonathanwosen.bsky.social
- Reposted by Steven Cheng🎉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...
- Chemoproteomic Profiling of Clickable Fumarate Probes for Target Identification and Mechanism of Action Studies pubs.acs.org/doi/10.1021/... from Biogen
- Reposted by Steven ChengOur 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...
- Reposted by Steven ChengCDC'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.
- Reposted by Steven ChengDistinct Classes of Gut Bacterial Molybdenum-Dependent Enzymes Produce Urolithins biorxiv.org/content/10.1101/202…
- Reposted by Steven ChengBREAKING: David Lynch, the visionary filmmaker behind "Blue Velvet," "Twin Peaks" and "Mulholland Drive," has died at 78. apnews.com/article/davi...
- Reposted by Steven ChengThe unique pharmacology of targeted degraders (eg PROTACs) leverages their sub-stoichiometric “catalytic” activity. Now Lycia Tx reports catalytic (cata)LYTACs for potent, durable extracellular #TPD, cleared IgE in NHPs, superior to omalizumab 👏 www.biorxiv.org/content/10.1...
- "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"
- Context-dependent translation inhibition as a novel oncology therapeutic modality biorxiv.org/content/10.1101/202…
- 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."
- www.nature.com/articles/s41... Tyrosine ubiquitination!
- Reposted by Steven ChengThe Brutalist wins Best Motion Picture – Drama 🎥 #GoldenGlobes boxd.it/k4BO
- Reposted by Steven ChengInterested 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/...
- Reposted by Steven Cheng1/14 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.
- Reposted by Steven ChengWhy 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...
- Reposted by Steven ChengUsing FKBP12 DELs to discover FKBP12 glues www.cell.com/cell-chemica...
- Reposted by Steven ChengGlobal organelle profiling reveals subcellular localization and remodeling at proteome scale www.cell.com/cell/fulltex...
- Reposted by Steven Cheng#JimmyCarter 's post presidency was admirable in so many ways, but especially in relation to the work he did to rid the world of some awful diseases. www.statnews.com/2024/12/29/h...
- Reposted by Steven ChengIt'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...
- Reposted by Steven ChengWe 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?
- Parallel Proteomic and Transcriptomic Microenvironment Mapping (μMap) of Nuclear Condensates in Living Cells From MacMillan lab pubs.acs.org/doi/10.1021/...
- Covalent Proximity Inducers @acspublications.bsky.social Chem Rev by Nir London Clever graphical abstract 🎨 pubs.acs.org/doi/10.1021/...
- Reposted by Steven ChengExciting news from Palleon Pharma. Engineered sialidases remove glyco-immune checkpoint ligands from B cells, thereby potentiating antibody-mediated B cell depletion for treatment of autoimmune disease. Clinical studies gearing up in partnership with Henlius Biotech #glycotime
- Reposted by Steven ChengWe've just joined Bluesky 🎉 Follow us for research, news, comment and opinion from Nature journal 🧪
- Reposted by Steven Cheng#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...
- Reposted by Steven ChengCDC 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 🧪
- Reposted by Steven ChengOne of the biggest questions we get is when will our journals be here. We thank you for your patience. You can now follow our journals with this starter pack!at://did:plc:jyctnrcv5dznuu67bkjjlf3t/app.bsky.graph.starterpack/3ldlmb4vlmi2q
- Reposted by Steven ChengI’m excited to share our latest study led by @giuliapasquesi.bsky.social out today in @cellpress.bsky.social , uncovering a new way transposons have been repurposed for human interferon signaling! Read on for a thread on cryptic splice variants, decoy receptors, and viruses (1/N) 👇🧵 #TESky 🧪
- Reposted by Steven ChengWe just posted a preprint about a death mechanism that we find truly surprising. When you turn off transcription, cells die (duh!)... but did you know this happens due to loss of Pol II itself, not loss of Pol II activity!?! preprint here and a thread (1/n): www.biorxiv.org/content/10.1... 🧪
- TIL there's an E3 ligase named "itchy"
- Discovery of molecular glues that bind FKBP12 and novel targets using DNA-barcoded libraries biorxiv.org/content/10.1101/202…
- Reposted by Steven ChengScience’s 2024 Breakthrough of the Year is lenacapavir, an injectable drug that demonstrated remarkable success at preventing HIV infection with one shot every 6 months. Learn more about this year's #BOTY and other big advances in science: scim.ag/3BrCtUn
- Reposted by Steven ChengToday 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
- Reposted by Steven ChengDivalent siRNA for prion disease biorxiv.org/content/10.1101/202…
- www.nature.com/articles/s41... Aromatic ring-opening metathesis 🤨
- Reposted by Steven ChengReally excited to see this work out! In collaboration with Prof. Jen Prescher, we showed that their cyclopropenone labeling strategy can be applied to structured RNA! Thrilled to work with this fantastic team of scientists. pubs.acs.org/doi/10.1021/...
- Reposted by Steven ChengCheck out this new work from Rhiju Das and coworkers @stanfordmedicine.bsky.social, large ornate RNAs form homooligomeric stable complexes, not so different from proteins after all
- Naturally ornate RNA-only complexes revealed by cryo-EM biorxiv.org/content/10.1101/202…
- Reposted by Steven ChengWe’re excited to announce that the ACS Division of Medicinal Chemistry is now on Bluesky! 🦋🔵 Follow us for updates on awards & fellowships, meetings, webinars, editorials, and all things MEDI. Stay connected with the latest news from the Division! 📣
- Reposted by Steven ChengHello, #MedSky community! We’re excited to begin our Bluesky journey. Here is a sampling of the trusted, influential, and essential information you can expect when you follow us:
- Reposted by Steven ChengNow on biorxiv! The JUMP-Cell Painting Consortium’s paper: “Morphological map of under- and over-expression of genes in human cells” This is the genetic perturbation portion of the JUMP’s dataset; our chemical perturbation paper will come in a few months www.biorxiv.org/content/10.1...
- Reposted by Steven ChengWe’re thrilled to share our Nature Methods review on #CellPainting — your go-to resource for mastering Cell Painting! From MOA and toxicity prediction to contributing to candidate drugs in clinical trials, we’ve distilled 10 years of insights!
- Reposted by Steven ChengWe have dramatically increased the activity of splice switching *and* RNase H-active antisense oligonucleotide #ASO therapeutics by conjugating a nuclear importer 🧬💊! Preprint led by Disha #chemsky 🧪 @uclchemistry.bsky.social @oxfordchemistry.bsky.social chemrxiv.org/engage/chemr...
- Reposted by Steven ChengAfter the medicine Nobel was given to Victor Ambros but not his wife (and 1st author on their landmark paper) Rosalind Lee, I got curious about what their story has to teach us about incentive structures in science. The reality is at once messier and more profound: www.statnews.com/2024/12/06/n...
- Reposted by Steven ChengSomatic FBXW7-R465C mutant shows promise in targeted protein degradation in cancer cells. This approach enhances protein degradation specificity in diseased cells. Congrats Xiaoyu Zhang and colleagues. 🧪 #chembio #TPD #CancerResearch www.biorxiv.org/content/10.1...
- Reposted by Steven Cheng5 years ago, Arrakis announced progress on a chemist's dream: Drugging RNA instead of proteins. The goal: Reach undruggable cancer targets, like myc It's been a long and bumpy road since then, @gilman.bsky.social explains. But there's been progress www.statnews.com/2024/12/04/a...
- Reposted by Steven Chengwith the antagonist, leading to relief of receptor inhibition. Drug or agonist can then turn on PAGER. www.nature.com/articles/s41...
- Reposted by Steven ChengCould one envision a synthetic receptor technology that is fully programmable, able to detect diverse extracellular antigens – both soluble and cell-attached – and convert that recognition into a wide range of intracellular responses, from gene expression and real-time fluorescence to modulation..
- Reposted by Steven ChengThat awkward moment when someone publishes a paper saying that they can’t find any evidence that your compounds bind to what your own series of papers say that they bind to. . .
- Reposted by Steven ChengCool new work from Jenn Prescher and coworkers @ucirvine.bsky.social, “RNA lantern” technology for bioluminescence imaging of RNA transcripts www.nature.com/articles/s41...
- Reposted by Steven ChengIt is always best to get scooped on a project before you put much work on it. Really cool preprint by Taylor Mighell and Ben Lehner on the effect of binder molecules on general rescue effect of destabilizing variants. Should work with protein binders as well. www.biorxiv.org/content/10.1...
- Reposted by Steven ChengNovartis is returning to Huntington’s disease with a $1 billion upfront bet, plus another $1.9 billion in biobucks, for access to a Phase 2 oral drug. endpts.com/novartis-pay...
- Reposted by Steven ChengFluorescently labeled proteins are essential to research. But we should never forget how messed-up their behavior can be. An example from condensates:
- Great resource for HTS assay development/PAINS filtering A Collection of Useful Nuisance Compounds (CONS) for Interrogation of Bioassay Integrity pubs.acs.org/doi/10.1021/...
- Reposted by Steven Cheng
Assume all small molecules are unselective for their protein target until proven otherwise. Even if the vendor tells you it’s a selective inhibitor for X, there’s a decent chance it isn’t selective! So how do we find quality molecules for scientific experiments? academic.oup.com/nar/advance-...
