Andrii Gorelik
Sir Henry Wellcome Fellow | Oxford with Ivan Ahel & Harvard with Steve Gygi
Molecular mechanisms of cysteine modifications | GlcNAc and ADP-ribose
Previously: The Francis Crick Institute/Imperial College London (postdoc), University of Dundee (PhD)
- Reposted by Andrii GorelikJust two more days to submit abstracts for the "PARP Family and ADP-ribosylation CSHL meeting. We have an amazing lineup of speakers. The majority of speakers are selected from abstracts. Don't miss out! meetings.cshl.edu/meetings.asp...
- Reposted by Andrii GorelikNew year, new preprint! 🎊 We are excited to share our recent work on #E3 ligase regulation in #metabolism! www.biorxiv.org/content/10.6... #ubiquitin #targetedproteindegradation #chemicalbiology 1/6
- Reposted by Andrii GorelikLearn more about the interplay between ADP-ribosylation and ubiquitination: PARG regulates proteasomal degradation of the ADP-ribosyl hydrolase TARG1 by preventing PAR-dependent ubiquitination mediated by the E3 ligases HUWE1 and TRIP12 www.sciencedirect.com/science/arti...
- Check out our latest story on AHR and PARP7 (TIPARP) degradation by the ADP-ribose-targeting E3 ligase DTX2 in the first issue of 2026 @embojournal.org! link.springer.com/article/10.1...
- Reposted by Andrii GorelikThrilled to share our latest study, led by @reikatei.bsky.social, in @natchembio.nature.com! We began by asking a simple question—how do cells know if they have too much of a lipid in a particular membrane, and how do they respond to rectify this imbalance? www.nature.com/articles/s41... More info 👇
- Reposted by Andrii GorelikIs arginine the new cysteine?! Check out our lab's latest in collaboration with @ianseiple.bsky.social's team where we introduce ninhydrin as a selective covalent warhead and probe targeting reactive arginines. www.biorxiv.org/content/10.6...
- Reposted by Andrii GorelikOnline now! Online now! An interactive resource mapping the proteome and reactive cysteine landscape across the NCI-60 reveals cell and tissue-specific profiles #chembiol
- Reposted by Andrii GorelikI have a PhD position available with start date September 2026 at the University of Manchester. Proteomics analysis of flow cytometry-based isolated pathogen-containing phagosomes Due to funding requirements, this position is for UK home students only. www.findaphd.com/phds/project...
- Reposted by Andrii GorelikSAVE THE DATE! The EMBO workshop "Ubiquitin and Ubiquitin-like proteins in Health and Disease" will be on September 2026. Exciting line up of talks and an amazing location! Organised by @kulathu.bsky.social, @merbllab.bsky.social, @simonapolo.bsky.social, Claudio Joazeiro. Registration open soon.
- Reposted by Andrii GorelikVery happy to share our collaborative project on FAM118 proteins - noncanonical sirtuins that form filaments and process NAD in human and other vertebrate cells.
- In our latest study we show that ligand-activated transcription factor AHR (environmental sensor) is ADP-ribosylated by PARP7. This ADP-ribose mark is recognised by the E3 ubiquitin ligase DTX2 targeting AHR for proteasomal degradation, enabling cells to rapidly shut down AHR-mediated transcription.
- This mechanism fits nicely with our previous report showing that AHR activation increases sensitivity to PARP7 inhibition in lung cancer cells. When PARP7 is inhibited (no ADP-ribosylation = no DTX2 interaction), AHR is stabilised in the nucleus and drives excessive transcription of its targets
- Reposted by Andrii GorelikMono-ADP-ribosylation as a degradation mark? @andriigorelik.bsky.social, Ivan Ahel et al observe increased ADP-ribosylation of aryl hydrocarbon receptor (AHR) & PARP7 upon ubiquitin-proteasome blockage, crosstalk with DTX2 E3, as rapid AHR-transcription off-switch www.embopress.org/doi/full/10....
- Reposted by Andrii GorelikOnline now! CBX4 acetoacetylation as an inhibitory mechanism of HIF-1α activity #chembiol
- Out in @natcomms.nature.com: Cryo-EM structure of the pseudo-HAT-containing O-GlcNAcase! Especially exciting since multiple companies are developing O-GlcNAcase inhibitors for Alzheimer's disease (tau is O-GlcNAcylated). Glad to have a small contribution in this story. Congrats to all authors!
- Reposted by Andrii GorelikHistorically, viruses were thought to primarily use host cell's translational machinery. New work from @harvardcellbio.bsky.social faculty Amy Lee reveals that a giant DNA virus encodes its own IF4F initiation complex, suggesting an unexpected evolutionary innovation. www.biorxiv.org/content/10.1...
- Reposted by Andrii GorelikNew work from our own Chouchani Lab finds that LRRC58 is the substrate adaptor of an E3 ubiquitin ligase that mediates proteasomal degradation of CDO1, the rate-limiting enzyme of the catabolic shunt of cysteine to taurine in response to altered Cysteine levels. www.nature.com/articles/s41...
- Reposted by Andrii GorelikRobert Redford (RIP) survived a childhood bout of polio though bedridden for 2 weeks In 2014, he directed a short film on the architecture and mission of La Jolla's Salk Institute—honoring founder Jonas Salk, inventor of the polio vaccine that has saved countless lives, and architect Louis Kahn
- Reposted by Andrii GorelikA few years back we discovered a dual hybrid protein modification composed of an ADP-ribose dinucleotide and the ubiquitin moieties (ADPr-Ub). Here you can read our review that will give you an update on this increasingly popular topic: rdcu.be/eETIT
- Reposted by Andrii GorelikDelighted to share our work on cellular ubiquitination of drug-like compounds by HUWE1 - a surprising journey! Kudos to all contributors & first authors, Barbara Orth and Pavel Pohl. Sincere thanks to @ireserra.bsky.social #NatCommun for expertly guiding the winding publishing path. rdcu.be/eDzPk
- Reposted by Andrii GorelikAre you a postdoc interested in the mechanisms of disease? Do you have a great record and an exciting vision? Come and start your own lab @dunnschool.bsky.social by applying for sponsorship for early career fellowships. Deadline 30th September...pass it on! www.path.ox.ac.uk/work-with-us...
- Happy to share that my first-author paper from my postdoc at Imperial @imperialcollegeldn.bsky.social and The Francis Crick Institute @crick.ac.uk is now published in Cell Reports! www.sciencedirect.com/science/arti...
- We screened hundreds of cancer cell lines using a potent and selective N-myristoyltransferase inhibitor (NMTi) and found a strong correlation between increased NMTi sensitivity and MYC deregulation with death of high (vs low) MYC cancer cells.
- Using proteomics, we discovered that NMTi cause mitochondrial dysfunction (complex I defects) in high-MYC cancer cells.
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View full threadCongratulations to first authors Gregor Lueg, James Zhang, Monica Faronato and big thanks to all co-authors for being amazing colleagues and collaborators! Special thanks to Ed Tate and Dinis Calado for supervising this exciting project!
- Reposted by Andrii GorelikWant to know how lipidation of some nascent chains takes place by NMT2-- Check our latest work on how NAC couples Protein Synthesis with Nascent Polypeptide Myristoylation on the Ribosome out today @embojournal.org: www.embopress.org/doi/full/10....
- Reposted by Andrii GorelikExcited to share a new preprint from the lab. We show that PTMs like phosphorylation & glycosylation dynamically reshape proteome-wide ligandability in cells, including proteins like KRAS. Great collaboration with the Huang Lab, @forlilab.bsky.social and BMS. www.biorxiv.org/content/10.1...
- Reposted by Andrii GorelikI still can’t believe that all NIH grants to my colleagues at Harvard and Harvard Medical School have been nullified. And that, as a nation, we’re somehow okay with this illegal, arbitrary, and petty act. Just think of the consequences: scientists, students, and patients will all suffer.
- Reposted by Andrii GorelikA few years back we discovered a dual hybrid protein modification composed of ADP-ribose dinucleotide and ubiquitin (ADPr-Ub). Now we reveal that ADPr-Ub can be further ubiquitinated by the E3 ubiquitin ligase RNF114! www.nature.com/articles/s41... www.science.org/doi/10.1126/...
- An amazing paper from van der Heden and Ahel groups! They use clever chemistry to identify RNF114 as a dual ADP-ribose-Ubiquitin reader involved in the DNA damage response! Congratulations to first authors Max, @chatrin-c.bsky.social and Rishov. Happy to have a small contribution in this story
- Reposted by Andrii GorelikThis is wild! Engineering E. coli bacteria to turn plastic waste into paracetamol (Tylenol) www.nature.com/articles/s41... www.nature.com/articles/s41...
- Reposted by Andrii GorelikA few years back we discovered a novel dual hybrid protein modification composed of ADP-ribose dinucleotide and ubiquitin (ADPr-Ub): pubmed.ncbi.nlm.nih.gov/36197986/
- New paper! We uncover mechanistic insights into the crosstalk between AHR (aryl hydrocarbon receptor, a transcription factor) and PARP7 (a nuclear enzyme that performs protein ADP-ribosylation). Both are promising cancer drug targets. Big thanks to all co-authors! www.pnas.org/doi/10.1073/...
- Transcriptomics is typically used to study transcription factors, but we took a different approach — examining proteome changes following PARP7 inhibition and AHR activation. This revealed post-translational events that contribute to the synthetic lethality via combined PARP7i and AHR activation.
- Plus, our CRISPR screen identified SOCS3 knockout as a new synthetic lethal interaction with PARP7i. Curiously, SOCS3 is also linked to AHR signalling.
- Big thanks to all co-authors at FGC in Cambridge, Hull, Oslo, NCI Frederick and of course @ahellab.bsky.social @dunnschool.bsky.social! I had a lot of fun doing proteomics in Steve Gygi’s lab @harvardcellbio.bsky.social funded by Sir Henry Wellcome Fellowship - thanks to @wellcometrust.bsky.social!
- Reposted by Andrii GorelikWe have another postdoc position available to work on interplay between ADP-ribosylation and ubiquitination in regulation of genome stability. For this post expertise in cell biology is required. my.corehr.com/pls/uoxrecru...
- Reposted by Andrii GorelikA postdoc position is available in our lab to study ADP-ribosylation and ubiquitylation signalling! We are looking for someone with experience in structural biology and biochemistry. The application deadline is June 20th. my.corehr.com/pls/uoxrecru...
- Reposted by Andrii GorelikNew work @harvard by Miguel Gonzalez-Lozano @harperlabhms.bsky.social & @ernstschmid.bsky.social in Johannes Walter lab charts structural interactome of endosomes. #XL-MS #Alphafold Funded by @asapresearch.parkinsonsroadmap.org & NIH. Science continues-despite attacks www.nature.com/articles/s41...
- Reposted by Andrii GorelikProtein degradation in E. coli via N-terminal degradation signals (degrons) defined by the @kunjapur.bsky.social lab. @ispt-proteinterm.bsky.social www.biorxiv.org/content/10.1...
- Reposted by Andrii GorelikI’m very excited to share our latest publication characterising the substrate binding interactions of an N-terminal cysteine oxidase (NCO), out now in @natcomms.nature.com! doi.org/10.1038/s414...
- Reposted by Andrii GorelikSharing the next installment of our fun collaboration with @michaelnadbio.bsky.social at the interface of #ubiquitin and #ADP-ribosylation! Building upon our identification of cellular MARUbylation, we now identify reader/writer E3 ligases that extend K11 polyUb! 🧵 www.biorxiv.org/content/10.1...
- Reposted by Andrii GorelikPass it on. #StandWithUkraine
- Reposted by Andrii GorelikDid you recently complete a ChemBio/MedChem PhD (non-UK) and are looking for the next challenge? I am seeking a prospective applicant for a Newton Fellowship with an exciting project in targeted protein dephosphorylation! Please reach out to e.devita@qmul.ac.uk royalsociety.org/grants/newto...
- Reposted by Andrii GorelikThanks to the more than *1100* members of the scientific community who have signed the letter to insist that the Royal Society remains true to values that we all hold dear but that Musk FRS has ridden roughshod over. Please keep signing & sharing. docs.google.com/forms/d/e/1F...
- Reposted by Andrii GorelikHappy to share our new study showing that the Ub E3 ligase SIAH1, known to dimerise via its C-term SBD, also dimerises via its N-term RING. When these tendencies combine, full-length SIAH1 forms multimers, which might explain its clustering in cells & preference for aggregated/multimeric substrates.
- Reposted by Andrii Gorelik🚨 The #Ubiquitin Congress is back in Würzburg! 🚨 Excited to host it again, June 2-4, 2025! 🌟 ✨ Still time to submit your abstract for a Short Talk! 🗓️ Registration Deadline: March 1st 📝 Abstract Submission Deadline: April 15th Don’t miss out—register now! ➡️ www.ubiquitin-wuerzburg-2025.de
- Reposted by Andrii GorelikNovel proteins regulated by hypoxia and the Arg/N-degron pathway. Cysteine-starting proteins such as IP6K1 and PIFO are oxidized by ADO, arginylated by ATE1 and ubiquitylated by UBRs. @ispt-proteinterm.bsky.social www.biorxiv.org/content/10.1...
- Reposted by Andrii GorelikI am experiencing an alarming increase in papers to review with an inimmaginabile amount of data already at submission. Sometimes 8 figures each with panels from a to z. Ungraspable complexity of an apparent 'mechanism', but often no clear message. Not nice. Has anyone observed this or is it me?
- Reposted by Andrii GorelikThe ASBMB "O-GlcNAc 🟦 in Health and Disease" conference is coming to Duke University, July 11-13, 2025! Thrilled to co-chair with Mike Boyce 🙌 Confirmed speakers in comments👇 Can’t wait to see you there! 🙌 asbmb.org/meetings-eve... #glycotime #ASBMB
- Reposted by Andrii GorelikThrilled to share our new paper @Chouchani Lab in Cell; what a great way to end this year! We establish a deep mapping of the zinc-binding human cysteine proteome (ZnCPT) and discover glutathione reductase as zinc-targetable cancer vulnerability. www.cell.com/cell/fulltex...
