Sean Rudd

Inference of Cancer Drug Cross Resistance Using Only Single-Drug Exposure Data https://www.biorxiv.org/content/10.64898/2026.03.10.709822v1

Macrophage-specific Ak4 regulates mtDNA synthesis, through which it controls mitochondrial biogenesis and mtROS levels and, subsequently, bacterial killing
rupress.org/jem/article/... @jem.org

FEBS Press Cytarabine is a key therapy for acute myeloid leukaemia (AML), but its efficacy is limited by the dNTPase SAMHD1, which hydrolyses its active metabolite. Screening nucleotide biosynthesis inhibitors ...

Happy to share the second paper from the group this year, out in @moloncology.bsky.social

Another story about the dNTPase & drug resistance factor SAMHD1 and our attempts to find ways to suppress its activity in cancer cells 👇

febs.onlinelibrary.wiley.com/doi/10.1002/...

@scilifelab.se @ki.se

FEBS Press Cytarabine is a key therapy for acute myeloid leukaemia (AML), but its efficacy is limited by the dNTPase SAMHD1, which hydrolyses its active metabolite. Screening nucleotide biosynthesis inhibitors ...

Happy to share the second paper from the group this year, out in @moloncology.bsky.social

Another story about the dNTPase & drug resistance factor SAMHD1 and our attempts to find ways to suppress its activity in cancer cells 👇

febs.onlinelibrary.wiley.com/doi/10.1002/...

@scilifelab.se @ki.se

With Eugene Koonin, we propose a concept of “the selfish ribosome”, under which evolution of life is viewed as a ribosomal takeover, where the ribosome evolved to consume most of the cell’s resources, while other cellular componentry ensures the propagation of the ribosome. arxiv.org/abs/2602.23268

Functional nutrient-genetic profiling reveals biotin and FBXW7 are essential to bypass glutamine addiction Lisci et al. present a unified model revealing how cells escape glutamine addiction, a metabolic vulnerability of several cancers. Combining systematic genetic and nutrient screens, they show that bio...

Our story on #FBXW7 and #biotin in #glutamine_addiction is now peer-reviewed and published in Molecular Cell! Heroic work led by the very first postdoc of the lab @miriamlisci.bsky.social. Have a look!

www.cell.com/molecular-ce...

This is correct

My objection to LLMs is not about form but substance: writing is about the only thing a PI actually produces. LLM coaching makes writing yet another task where we're managers instead of makers. It's the final victory of the managerial model – same reason why I'm also against outsourcing research

This is absolutely the opposite of how I understand academic writing

Allosteric targeting with antiviral nucleotide analogues allows fine-tuning of SAMHD1 dNTPase activity SAMHD1 is a deoxyribonucleoside triphosphate (dNTP) hydrolase that controls intracellular dNTP pools and plays diverse roles in human health and disease. Notably, this enzymatic activity also confers ...

Excited to share the latest research from the group!

We have a new paper out in @asbmbjournals.bsky.social led by our first PhD student!

Here we look at the enzyme SAMHD1, a key player in dNTP metabolism and chemotherapy resistance

www.jbc.org/article/S002...

cc @scilifelab.se @ki.se

🧵

20 new Technology Development Projects funded as call strengthens collaboration across and beyond SciLifeLab SciLifeLab recently decided on 20 Technology Development Projects (TDPs) for funding in the latest TDP call. TDPs are projects aimed at developing new technologies, methods or workflows, often as…

20 new Technology Development Projects funded as call strengthens collaboration across and beyond SciLifeLab. 🧪

A goal of the TDPs is that the developed technologies will eventually be offered as new services to the user community.

More & list of projects ↓

Large-scale mapping of environmental-genetic interactions illustrates the dynamic nature of cell-cycle and DNA repair regulation To date, genetic interaction (GI) maps in the context of environmental perturbations have been limited to yeast studies. Herken et al. present five human GI maps that reveal how the landscape of genes...

This work shows that gene function is not fixed but dynamically shaped by a cell’s environment, and that mapping those shifts can reveal biology invisible to single-condition screens.

Download the full paper: www.cell.com/molecular-ce...

Congratulations to Sonomi Yamaguchi for her paper at @nature.com. Sonomi discovered Clover defense and explained how nucleotide signals control each step of viral sensing, immune regulation, and viral restriction – named for her beautiful "four-leaf" structures 🍀

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

A Pan-Cancer Ex Vivo Drug Screen Atlas for Functional Precision Oncology https://www.biorxiv.org/content/10.64898/2026.02.14.705918v1

Recognizing dUTPase as a mitotic factor essential for early embryonic development https://www.biorxiv.org/content/10.64898/2026.01.16.699898v1

Can check out the full paper here (there is a couple more interesting things in there...)

👇👇👇
www.jbc.org/article/S002...

Very grateful to the team & collaborators

And of course the funders - particularly Cancerfonden and Barncancerfonden - together with doctoral funding from @ki.se

Cheers!

We think this differential activity can be largely explained by distinct kinetic profiles that deviate from the usual with this enzyme

But what we're quite excited about is the implication that we can fine-tune activity of SAMHD1 via non-natural allosteric site ligands

We found these analogues can activate SAMHD1, binding to the allosteric site with a higher affinity than the physiological ligand GTP, and promote formation of a catalytically-competent tetramer

However, these tetramers have vastly (!) different activity profiles...

SAMHD1 is allosterically regulated by nucleotides with one of the allosteric sites being specific for the guanine nucleotide GTP

So here we asked how analogues of GTP - specifically the active metabolites of anti-viral agents acyclovir and ganciclovir - work as allosteric effectors

SAMHD1 is a dNTP hydrolase that we've previously shown can deactivate a bunch of cancer drugs whose active metabolites mimic dNTPs (i.e., nucleoside analogues)

So one thing we are looking at in the lab is how we can control the activity of this enzyme with small molecules

Allosteric targeting with antiviral nucleotide analogues allows fine-tuning of SAMHD1 dNTPase activity SAMHD1 is a deoxyribonucleoside triphosphate (dNTP) hydrolase that controls intracellular dNTP pools and plays diverse roles in human health and disease. Notably, this enzymatic activity also confers ...

Excited to share the latest research from the group!

We have a new paper out in @asbmbjournals.bsky.social led by our first PhD student!

Here we look at the enzyme SAMHD1, a key player in dNTP metabolism and chemotherapy resistance

www.jbc.org/article/S002...

cc @scilifelab.se @ki.se

🧵

We carried out a mechanistic study on how the PCBP1 protein destabilizes i-motifs. Understanding these interactions helps clarify fundamental mechanisms that control genome function.
Grateful for the long-term support we have received! @kawresearch.bsky.social @mbb-umu.bsky.social
rdcu.be/e2pIv

DNA-protein cross-links promote cGAS-STING–driven premature aging and embryonic lethality DNA-protein cross-links (DPCs) are highly toxic DNA lesions that block replication and transcription, but their impact on organismal physiology is unclear. We identified a role for the metalloprotease...

Unrepaired DNA-protein crosslinks cause a process that leads to premature aging and embryonic lethality in mice.

The findings in Science reveal a previously unrecognized link between defective DNA repair and immune-driven inflammatory disease. https://scim.ag/4qdZWf9

"authors also express frustration at the amount of work expected for a single publishable unit, a concern we
share (while humbly noting that it may not be
held by the same authors when they serve as
reviewers of other work)" <-THAT www.nature.com/articles/s41... ht @ritastrack.bsky.social

Thoughts of an Ex-Editor - Psychopharmacology Psychopharmacology -

apropos of absolutely nothing, a lot of scientists could profit from reading this editorial from legendary Conan Kornetsky upon retiring from an editor position.
link.springer.com/article/10.1...

PAF15–PCNA exhaustion governs the strand-specific control of DNA replication Nature - PCNA–PAF15 has a key role in determining replisome dynamics during genome replication and protecting against genome instability.

Dear Colleagues,

Delighted to share that our first lab paper is now published in Nature.!!! 😊😊😊

We identify a previously concealed “safety limit” in DNA replication program: cells intrinsically rate-limit PCNA via PAF15, shaping strand-specific and global replication dynamics.

👉 rdcu.be/e1bBt

Obesity rewires nucleotide metabolism in immune cells, making inflammatory responses via NLRP3 inflammasome much easier to trigger
www.science.org/doi/10.1126/... @science.org @zhenyuzhong.bsky.social @utswim.bsky.social

Want to get the data out of a PDF figure? As in, the actual data – not a rough trace-along-the-lines version?

I made an app you might like: adamkucharski.github.io/pdf2plot/

It all started a few years ago... 🧵

Defending PhD student, looking over their thesis: “If I knew then what I know now, I could’ve done all of this in like 9 months.”

A thread about my favorite pioneering cave explorers and why I don’t think AI will ever “solve” biology.

Deep contrastive learning enables genome-wide virtual screening Recent breakthroughs in protein structure prediction have opened new avenues for genome-wide drug discovery, yet existing virtual screening methods remain computationally prohibitive. We present DrugC...

@science.org Deep contrastive learning enables genome-wide virtual screening | Science www.science.org/doi/10.1126/...