Andrii Gorelik
@andriigorelik.bsky.social
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)
Molecular mechanisms of cysteine modifications | GlcNAc and ADP-ribose
Previously: The Francis Crick Institute/Imperial College London (postdoc), University of Dundee (PhD)
Pinned
Andrii Gorelik
@andriigorelik.bsky.social
· Jun 11
PNAS
Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans...
www.pnas.org
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/...
Big thanks to all co-authors!
www.pnas.org/doi/10.1073/...
Reposted by Andrii Gorelik
Online now! CBX4 acetoacetylation as an inhibitory mechanism of HIF-1α activity #chembiol
CBX4 acetoacetylation as an inhibitory mechanism of HIF-1α activity
Li et al. identify XZA-1 as a small-molecule activator of HADH that increases acetoacetyl-CoA, inducing CBX4 K106 acetoacetylation. This modification suppresses CBX4 SUMO E3 ligase activity, reduces HIF-1α SUMOylation, and attenuates its transcriptional activity.
dlvr.it
October 7, 2025 at 3:30 PM
Online 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!
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!
Multi-domain O-GlcNAcase structures reveal allosteric regulatory mechanisms - Nature Communications
This work reveals how a regulatory domain in O-GlcNAc hydrolase (OGA) shapes enzyme flexibility and activity, uncovering mechanisms that help maintain O-GlcNAc balance in cells.
www.nature.com
October 6, 2025 at 2:16 PM
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!
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 Gorelik
Historically, 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...
Giant DNA viruses encode a hallmark translation initiation complex of eukaryotic life
In contrast to living organisms, viruses were long thought to lack protein synthesis machinery and instead depend on host factors to translate viral transcripts. Here, we discover that giant DNA virus...
www.biorxiv.org
October 2, 2025 at 6:10 PM
Historically, 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 Gorelik
New 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...
Covariation MS uncovers a protein that controls cysteine catabolism - Nature
A mass spectrometry-based approach globally identifies protein regulators of metabolism and reveals the role of LRRC58 in controlling cysteine catabolism.
www.nature.com
September 17, 2025 at 5:48 PM
New 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 Gorelik
Robert 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
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
CATHEDRALS OF CULTURE - Clip ROBERT REDFORD: Salk Institute -- La Jolla, California, USA - HD
YouTube video by neueroadmovies
youtu.be
September 17, 2025 at 2:52 AM
Robert 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
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 Gorelik
A 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
rdcu.be/eETIT
The rise of ADP-ribose–ubiquitin
Nature Structural & Molecular Biology - Post-translational modifications show mechanistic crosstalk, exemplified by the ADP-ribose–ubiquitin hybrid signal, in which one post-translational...
rdcu.be
September 8, 2025 at 3:24 PM
A 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
rdcu.be/eETIT
Reposted by Andrii Gorelik
Delighted 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
rdcu.be/eDzPk
Selective ubiquitination of drug-like small molecules by the ubiquitin ligase HUWE1
Nature Communications - Ubiquitination is a versatile modification system in eukaryotic cells. Here, the authors unveil that the ubiquitin ligase HUWE1 can modify drug-like small-molecule...
rdcu.be
September 2, 2025 at 11:55 AM
Delighted 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
rdcu.be/eDzPk
Reposted by Andrii Gorelik
Are 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...
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...
Group Leader Career Development Fellowships - Dunn School
Are you an early career researcher interested in the cell or molecular mechanisms underlying disease? Do you have an outstanding record and an innovative research plan?
www.path.ox.ac.uk
September 1, 2025 at 2:39 PM
Are 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...
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...
www.sciencedirect.com/science/arti...
MYC deregulation sensitizes cancer cells to N-myristoyltransferase inhibition
Human N-myristoyltransferases (NMTs) catalyze N-terminal protein N-myristoylation and are promising targets in cancer, with an emerging mechanistic ra…
www.sciencedirect.com
August 28, 2025 at 1:16 PM
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...
www.sciencedirect.com/science/arti...
Reposted by Andrii Gorelik
Want 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....
August 26, 2025 at 11:00 AM
Want 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 Gorelik
Excited 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...
Post-Translational Modifications Remodel Proteome-Wide Ligandability
Post-translational modifications (PTMs) vastly expand the diversity of human proteome, dynamically reshaping protein activity, interactions, and localization in response to environmental, pharmacologi...
www.biorxiv.org
August 3, 2025 at 2:36 PM
Excited 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 Gorelik
I 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.
July 18, 2025 at 3:30 AM
I 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 Gorelik
A 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/...
www.nature.com/articles/s41...
www.science.org/doi/10.1126/...
Identification of RNF114 as ADPr-Ub reader through non-hydrolysable ubiquitinated ADP-ribose - Nature Communications
Deltex E3s modify ADP-ribosylated targets with ubiquitin, creating a hybrid modification whose readers remains unknown. Here, the authors synthesise a non-hydrolysable probe that mimics the modificati...
www.nature.com
July 10, 2025 at 6:11 AM
A 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/...
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
Identification of RNF114 as ADPr-Ub reader through non-hydrolysable ubiquitinated ADP-ribose - Nature Communications
Deltex E3s modify ADP-ribosylated targets with ubiquitin, creating a hybrid modification whose readers remains unknown. Here, the authors synthesise a non-hydrolysable probe that mimics the modificati...
www.nature.com
July 10, 2025 at 10:44 AM
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 Gorelik
This is wild!
Engineering E. coli bacteria to turn plastic waste into paracetamol (Tylenol)
www.nature.com/articles/s41...
www.nature.com/articles/s41...
Engineering E. coli bacteria to turn plastic waste into paracetamol (Tylenol)
www.nature.com/articles/s41...
www.nature.com/articles/s41...
June 23, 2025 at 6:55 PM
This is wild!
Engineering E. coli bacteria to turn plastic waste into paracetamol (Tylenol)
www.nature.com/articles/s41...
www.nature.com/articles/s41...
Engineering E. coli bacteria to turn plastic waste into paracetamol (Tylenol)
www.nature.com/articles/s41...
www.nature.com/articles/s41...
Reposted by Andrii Gorelik
A 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/
pubmed.ncbi.nlm.nih.gov/36197986/
| bioRxiv
bioRxiv - the preprint server for biology, operated by Cold Spring Harbor Laboratory, a research and educational institution
www.biorxiv.org
May 24, 2025 at 5:45 AM
A 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/
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/...
Big thanks to all co-authors!
www.pnas.org/doi/10.1073/...
PNAS
Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans...
www.pnas.org
June 11, 2025 at 11:48 AM
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/...
Big thanks to all co-authors!
www.pnas.org/doi/10.1073/...
Reposted by Andrii Gorelik
We 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...
my.corehr.com/pls/uoxrecru...
'
my.corehr.com
June 6, 2025 at 4:48 AM
We 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...
my.corehr.com/pls/uoxrecru...
Reposted by Andrii Gorelik
A 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...
my.corehr.com/pls/uoxrecru...
'
my.corehr.com
May 24, 2025 at 5:29 AM
A 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...
my.corehr.com/pls/uoxrecru...
Reposted by Andrii Gorelik
New 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...
EndoMAP.v1 charts the structural landscape of human early endosome complexes - Nature
A study presents EndoMAP.v1, a resource that combines information on protein interactions and crosslink-supported structural predictions to map the interaction landscape of early endosomes.
www.nature.com
May 28, 2025 at 3:52 PM
New 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 Gorelik
Protein 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...
Combinatorial mutagenesis of N-terminal sequences reveals unexpected and expanded stability determinants of the Escherichia coli N-degron pathway
Although it is known that penultimate N-terminal residues can influence protein stability by the N-degron pathway, there has not been a comprehensive effort to document nor predict these effects for n...
www.biorxiv.org
May 23, 2025 at 2:04 PM
Protein 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 Gorelik
I’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...
doi.org/10.1038/s414...
An mRNA-display derived cyclic peptide scaffold reveals the substrate binding interactions of an N-terminal cysteine oxidase - Nature Communications
This work identified cyclic peptide inhibitors of a mammalian N-terminal cysteine oxidase, ADO, through mRNA display, one of which was used as a scaffold to graft substrate moieties, allowing key inte...
doi.org
May 23, 2025 at 6:07 AM
I’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...
doi.org/10.1038/s414...
Reposted by Andrii Gorelik
Sharing 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...
www.biorxiv.org/content/10.1...
A family of E3 ligases extend K11 polyubiquitin on sites of MARUbylation
Ubiquitin (Ub) cooperation with other post-translational modifications provides a tiered opportunity for protein regulation. Small modifications to Ub such as phosphorylation, acetylation, or ADP-ribo...
www.biorxiv.org
May 17, 2025 at 2:45 PM
Sharing 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...
www.biorxiv.org/content/10.1...
Reposted by Andrii Gorelik
Reposted by Andrii Gorelik
Did 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 [email protected]
royalsociety.org/grants/newto...
royalsociety.org/grants/newto...
royalsociety.org
February 17, 2025 at 7:21 AM
Did 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 [email protected]
royalsociety.org/grants/newto...
royalsociety.org/grants/newto...