@seanrudd
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
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
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
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
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. 🧪
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 ↓
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!
Model from the paper. In the presence of GTP analogues, SAMHD1 forms homotetramers that are catalytically competent, but display reduced catalytic activity with distinct kinetic profiles compared to those containing the endogenous activator GTP
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
Figure from the paper showing SAMHD1 dNTPase activity against different dNTPs when activated with GTP or GTP analogues acyclovir-/ganciclovir-triphosphate. Activity towards different dNTPs differ greatly. In particularly, dCTP hydrolysis is abolished.
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...
Figure from the paper detailing the allosteric activation of SAMHD1, which requires nucleotide binding at two distinct allosteric sites to generate the active tetramer. The first allosteric site is specific for guanine nucleotides. Also shown are the chemical structures of GTP and GTP-analogues acyclovir- and ganciclovir-triphosphate
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
Cartoon showing bio-activation of a nucleoside analogue cancer drug into its triphosphate metabolite, which is subsequently hydrolysed by the enzyme SAMHD1, rendering it ineffective.
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
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
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
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...
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.
@science.org Deep contrastive learning enables genome-wide virtual screening | Science www.science.org/doi/10.1126/...
I guess I should re-post from the Bird Site "The Rules For Academic Success here":
I always get asked for advice about starting/surviving the tenure track. Here are the rules I've found useful. Thought I'd put it out there for the masses...
This list gets longer all the time
This is a great and welcome acknowledgment that we need more publishing venues explicitly dedicated to limiting publication bias
journals.plos.org/plosbiology/...
