Sean Rudd
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seanrudd.bsky.social
Sean Rudd
@seanrudd.bsky.social
Group leader @ Karolinska Institutet & SciLifeLab in Stockholm, Sweden. Interested in understanding how cancer drugs work.

Lab site - https://www.seanruddlab.com/
Genome stability | dNTP metabolism | Cancer therapy
Pinned
New review article from the group diving into the interplay between DNA precursor pool metabolism and genome instability. A relationship that's fundamental to cancer biology and underpins a number of therapeutic approaches, including nucleoside analogues 👇

journals.biologists.com/dmm/article/...
Reposted by Sean Rudd
1/New paper from Zheng Wu, Phong Nguyen et al. @cri-utsw.bsky.social shows how cells balance the two pathways that produce purine nucleotides: de novo purine biosynthesis (DNPB) and purine salvage. The surprising mechanism involves NUDT5, a Nudix hydrolase

www.science.org/doi/10.1126/...
NUDT5 regulates purine metabolism and thiopurine sensitivity by interacting with PPAT
Cells generate purine nucleotides through de novo purine biosynthesis (DNPB) and purine salvage. Purine salvage represses DNPB to prevent excessive purine nucleotide synthesis through mechanisms that ...
www.science.org
November 6, 2025 at 7:01 PM
Reposted by Sean Rudd
New preprint from the lab for any DNA repair or replication stress geeks out there!

www.biorxiv.org/content/10.1...
A nuclease-driven mechanism of post-replicative ssDNA gap suppression.
The persistence of post-replicative ssDNA gaps following PRIMPOL-mediated replication repriming is linked to chemosensitivity, and in all models reported to date the nuclease MRE11 has been implicated...
www.biorxiv.org
October 22, 2025 at 6:56 PM
Reposted by Sean Rudd
From descriptive to quantitative biocatalysis

“The 1913 study ‘Die Kinetik der Invertinwirkung’, by Michaelis and Menten, marked a pivotal advancement in enzymology by illustrating the application of mechanistic models and quantitative kinetics to biocatalysis.”

doi.org/10.1038/s419...
From descriptive to quantitative biocatalysis - Nature Catalysis
The 1913 study ‘Die Kinetik der Invertinwirkung’, by Michaelis and Menten, marked a pivotal advancement in enzymology by illustrating the application of mechanistic models and quantitative kinetics to biocatalysis. The foundational framework described back then continues to have a strong impact on enzymology, with profound influences that range from undergraduate education to structure–function studies and the format and content of contemporary kinetic databases.
doi.org
September 24, 2025 at 4:13 PM
Reposted by Sean Rudd
Ribonucleotide incorporation into mitochondrial DNA drives inflammation

www.nature.com/articles/s41...

Congratulations to the Langer lab @mpiage.bsky.social, Amir, and the rest of the team!
Ribonucleotide incorporation into mitochondrial DNA drives inflammation - Nature
Imbalanced nucleotide metabolism leads to age- and mtDNA-dependent inflammatory responses and senescence-associated secretory phenotype in senescence.
www.nature.com
September 24, 2025 at 4:31 PM
Reposted by Sean Rudd
Excited to share our lab’s latest preprint! We identify DDIAS as a novel single-stranded DNA-binding component of the TOPBP1–CIP2A complex, which acts in a mitotic DNA damage response pathway to protect chromosome integrity. Short summary below, and read it here: www.biorxiv.org/content/10.1...
DDIAS is a single-stranded DNA-binding effector of the TOPBP1-CIP2A complex in mitosis
DNA double-strand breaks and unresolved DNA replication intermediates are particularly dangerous during mitosis. Paradoxically, cells inactivate canonical DNA repair mechanisms during chromosome segre...
www.biorxiv.org
September 10, 2025 at 3:18 PM
Reposted by Sean Rudd
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
September 2, 2025 at 6:39 PM
Reposted by Sean Rudd
Glioblastoma, an aggressive brain cancer, depends on the amino acid serine as a fuel source

go.nature.com/4mIcCtD
Depriving brain tumours of an amino acid could enhance chemotherapy
Glioblastoma, an aggressive brain cancer, depends on the amino acid serine as a fuel source. A serine-deficient diet has been shown to slow tumour growth in mice.
go.nature.com
September 3, 2025 at 5:17 PM
Reposted by Sean Rudd
My first post on bsky to share our latest research in @nature.com: “DNA2 enables growth by restricting recombination-restarted replication” - defines DNA2’s essential function & elucidates links with primordial dwarfism and cancer. Thanks to the lab, collaborators & @ukri.org @acmedsci.bsky.social
DNA2 enables growth by restricting recombination-restarted replication - Nature
DNA2 suppresses recombination-restarted replication and checkpoint activation at stalled forks, and its loss triggers recombination-dependent synthesis, checkpoint signalling and cell-cycle exit, high...
www.nature.com
September 3, 2025 at 3:59 PM
Reposted by Sean Rudd
Check our new website – night-science.org – and consider also helping us to launch the Night Science Institute!
July 29, 2025 at 2:59 PM
Reposted by Sean Rudd
It is not always safe to repair DNA Damage. Sometimes, cells "just bypass it".

During DNA replication, repair of lesions on DNA can be dangerous. Cells instead "tolerate" DNA damage and focus on finishing replication.

Read our review and find out why and how: doi.org/10.1016/j.ti...
August 22, 2025 at 11:48 AM
Reposted by Sean Rudd
Classical macrophage activation reprograms nucleotide metabolism by suppressing de novo synthesis and enhancing salvage pathways (through nitric oxide...) @natmetabolism.nature.com doi.org/10.1038/s422... 🧪

Great N&V's on metabolic immune control by @ryanlab.bsky.social www.nature.com/artic...
Classically activated macrophages undergo functionally significant nucleotide metabolism remodelling driven by nitric oxide
Nature Metabolism - John et al. show that upon classical activation, macrophages undergo nitric oxide-driven reprogramming of nucleotide metabolism, which affects immune functions and responses.
doi.org
August 21, 2025 at 5:48 PM
Reposted by Sean Rudd
Reposted by Sean Rudd
New review: Mellor, Larson, and @drmengwang.bsky.social discuss the molecular mechanisms of mammalian genomic instability arising from folate deficiency and how this impacts genome biology in health and disease. rupress.org/jcb/article/...

#CellMetabolism
August 18, 2025 at 5:15 PM
Reposted by Sean Rudd
"if we do the work only for rewards and recognition, we have gone astray. It becomes hollow. Creative work of every sort (not just science) occurs in a niche where the inner drive to understand or express and the outer drive to be rewarded achieve some balance."
Why would anyone want to be a scientist?

Check out our new Essay from Martin Schwartz: journals.biologists.com/jcs/article/...
August 15, 2025 at 3:32 PM
Reposted by Sean Rudd
#ResearchHighlight 🚨
In a recent study, the Nussenzweig lab investigated the mechanisms underlying #cytarabine-induced neurotoxicity and provide a mechanistic explanation for the differing neurotoxicity profiles of #gemcitabine.
📖⬇️
Same same but different - Nature Reviews Cancer
In a recent study published in Nature, Liu, Wang, et al. investigate the mechanisms underlying cytarabine-induced neurotoxicity and provide a mechanistic explanation for the differing neurotoxicity profiles of other nucleoside analogues, such as gemcitabine.
www.nature.com
August 13, 2025 at 2:15 PM
Reposted by Sean Rudd
A paper from the JUMP Cell Painting Consortium presents image-based phenotypic profiles for 75% of the protein coding genome of human U-2 OS cells, offering a valuable resource for exploring gene relationships. @shantanu-singh.cc @drannecarpenter.bsky.social

www.nature.com/articles/s41...
August 7, 2025 at 8:01 PM
Reposted by Sean Rudd
Happy to share a paper from our lab out in @hemasphere-journal.bsky.social

-Resistance to antimetabolites, glucocorticoids & doxorubicin = poorer relapse-free survival
-Molecular profiling reveals pre-treatment resistance signatures

Huge thanks to all the co-authors and funders for their support
doi.org
August 4, 2025 at 5:25 AM
Reposted by Sean Rudd
On-target toxicity limits the efficacy of CDK11 inhibition against cancers with 1p36 deletions https://www.biorxiv.org/content/10.1101/2025.08.03.668359v1
August 4, 2025 at 4:48 AM
Reposted by Sean Rudd
We wrote a review on the free nucleotide pool as a central playground in human, bacterial, and plant immunity – now out in Nature Reviews in Immunology

www.nature.com/articles/s41...

Was fun to write this piece with Dina Hochhauser!

Here is a thread to explain the premises

1/
Manipulation of the nucleotide pool in human, bacterial and plant immunity - Nature Reviews Immunology
Modification of the nucleotide pool is emerging as key to innate immunity in animals, plants and bacteria. This Review explains how immune pathways conserved from bacteria to humans manipulate the nuc...
www.nature.com
July 30, 2025 at 6:05 AM
Reposted by Sean Rudd
Two is better than one: Pancreatic ductal adenocarcinoma cells can become resistant to treatment with autophagy inhibitors, but combination with pyrimidine analogues shows promise.

New #preLight by Hannah Pletcher covers the #preprint of Suzanne Dufresne and colleagues. Have a look!
Leveraging autophagy and pyrimidine metabolism to target pancreatic cancer - preLights
Two is better than one: Pancreatic ductal adenocarcinoma cells can become resistant to treatment with autophagy inhibitors, but combination with pyrimidine analogues shows promise.
prelights.biologists.com
July 25, 2025 at 12:48 PM
Reposted by Sean Rudd
Better version of the meme.
July 23, 2025 at 8:54 PM