Nick Valerie
LightNews LightNews
nckvalerie.bsky.social
Nick Valerie
@nckvalerie.bsky.social
190 followers 230 following 20 posts
Assistant Professor @ Karolinska Institutet, Stockholm, Sweden | Interested in understanding drug action 💊 and simplifying complex biology 🔬.

Cancer biology and metabolism | DNA repair | drug discovery | next-gen chemical biology | https://t.ly/uzrfe
Posts Replies Media Videos
Reposted by Nick Valerie
ki.se
Researchers have performed a large-scale genetic screen to uncover the hidden roles of #microproteins. One of the discovered microproteins, named PIPPI, was found to protect cells from stress in the endoplasmic reticulum. Published in @narjournal.bsky.social 🧪 #proteomics news.ki.se/new-micropro...
New microprotein can help cancer cells overcome stress
In a new study published in the journal Nucleic Acid Research, a research team at Karolinska Institutet has performed a large-scale genetic screen to uncover the hidden roles of tiny proteins, so-call...
news.ki.se
November 27, 2025 at 7:55 AM
nckvalerie.bsky.social
Happy to share a new preprint on NUDT5's role in regulating nucleoside analog (NA) drug efficacy. 🔗 👇

🧵: We show that perturbing NUDT5 abundance by RNAi or a PROTAC (DDD2), but not inhibition with TH5427, desensitizes cells to thiopurines and most NA drugs in a titratable manner.

1/n
biorxivpreprint.bsky.social bioRxivpreprint @biorxivpreprint.bsky.social · 15d
NUDT5 regulates the global efficacy of nucleoside analog drugs by coordinating purine synthesis and PRPP allocation https://www.biorxiv.org/content/10.1101/2025.11.20.689348v1
November 21, 2025 at 3:43 PM
Reposted by Nick Valerie
greenrat.bsky.social
Neat trick if you polycolonal ab's suck. Incubate them with fixed cells with a KO of your protein of interest, then spin. Protocol here: www.med.upenn.edu/markslab/ass...
I was amazed how well it worked on first try (I'm sure that I can completely eliminate unspecific bands)
#WesternBlot #cellsky
On the left - western blot of B16F10 cells wt and KO for CDK8. Our in house produced antibodies give a lot of unspecific bands. On the right same probes with antibodies preincubated with fixed CDK8 KO cells - there is a specific band and faint unspecific bands, which can be probably eliminated with increase of amount of KO cells.
October 2, 2025 at 5:11 PM
nckvalerie.bsky.social
@mortusewicz.bsky.social
biorxivpreprint.bsky.social bioRxivpreprint @biorxivpreprint.bsky.social · Oct 2
DNAi: an open-source AI tool for unbiased DNA fiber analysis https://www.biorxiv.org/content/10.1101/2025.09.30.679603v1
October 2, 2025 at 5:10 PM
Reposted by Nick Valerie
biorxivpreprint.bsky.social
DNAi: an open-source AI tool for unbiased DNA fiber analysis https://www.biorxiv.org/content/10.1101/2025.09.30.679603v1
October 2, 2025 at 1:17 PM
nckvalerie.bsky.social
🚨 Happy to finally share our first @biorxivpreprint.bsky.social on PROTACs and TPD with Mikael Altun and DDDP @scilifelab.se. 🚨

We develop a suite of cell-based methods to assess degrader functionality and show this with new PROTACs toward NUDT5 as PoC.

👇
www.biorxiv.org/content/10.1...

🧵 1/4
A cell-based degrader assessment platform facilitates discovery of functional NUDT5 PROTACs
Targeted protein degradation (TPD) via PROTACs and molecular glues holds significant therapeutic promise but demands detailed mechanistic evaluation in live cells to fully understand compound behavior...
www.biorxiv.org
June 25, 2025 at 10:21 AM
Reposted by Nick Valerie
nature.com
This phenomenon describes how those with an early advantage or success tend to accumulate over time

https://go.nature.com/45AJ1Ni
Early grant success attracts more funding: study of 100,000 applicants hints at why
Largest study of its kind explores the ‘Matthew effect’ in research.
go.nature.com
June 23, 2025 at 8:24 AM
Reposted by Nick Valerie
biorxivpreprint.bsky.social
NAD+ Sensing by PARP7 Regulates the C/EBPβ-Dependent Transcription Program in Adipose Tissue In Vivo https://www.biorxiv.org/content/10.1101/2025.04.07.647692v1
April 9, 2025 at 6:30 AM
Reposted by Nick Valerie
biorxivpreprint.bsky.social
Discovery of a VHL molecular glue degrader of GEMIN3 by Picowell RNA-seq https://www.biorxiv.org/content/10.1101/2025.03.19.644003v1
March 19, 2025 at 7:45 PM
Reposted by Nick Valerie
altmetric.com
THREAD

This Is The Story Of The The Pernicious Rise of AI-Generated Papers and their Online Impact

An Incomplete History Told In The Voice of Documentarian Adam Curtis
1/31
Adam Curtis Title Card: We Too Are Trapped In A System. Text over a background of a large office building
December 19, 2024 at 9:10 PM
Reposted by Nick Valerie
seanrudd.bsky.social
Great perspective on the importance of conventional chemotherapy.

Despite many many decades of successful use, do we understand how these drugs work?

www.nature.com/articles/s41...
Conventional chemotherapy: millions of cures, unresolved therapeutic index Article abstract In recent decades, millions of patients with cancer have been cured by chemotherapy alone. By ‘cure’, we mean that patients with cancers that would be fatal if left untreated receive a time-limited course of chemotherapy and their cancer disappears, never to return. In an era when hundreds of thousands of cancer genomes have been sequenced, a remarkable fact persists: in most patients who have been cured, we still do not fully understand the mechanisms underlying the therapeutic index by which the tumour cells are killed, but normal cells are somehow spared. In contrast, in more recent years, patients with cancer have benefited from targeted therapies that usually do not cure but whose mechanisms of therapeutic index are, at least superficially, understood. In this Perspective, we will explore the various and sometimes contradictory models that have attempted to explain why chemotherapy can cure some patients with cancer, and what gaps in our understanding of the therapeutic index of chemotherapy remain to be filled. We will summarize principles which have benefited curative conventional chemotherapy regimens in the past, principles which might be deployed in constructing combinations that include modern targeted therapies.
December 18, 2024 at 9:06 PM
Reposted by Nick Valerie
mafdawson.bsky.social
Thrilled to share a wonderful collaboration with Scott Armstrong, Florian Perner & Shellaina Gordon - exciting times ahead!

www.biorxiv.org/content/10.1...
Catalytic inhibition of KAT6/KAT7 enhances the efficacy and overcomes primary and acquired resistance to Menin inhibitors in MLL leukaemia
Understanding the molecular pathogenesis of MLL fusion oncoprotein (MLL-FP) leukaemia has spawned epigenetic therapies that have improved clinical outcomes in this often-incurable disease. Using genet...
www.biorxiv.org
December 13, 2024 at 9:07 PM
Reposted by Nick Valerie
mortusewicz.bsky.social
Very happy to have been able to contribute to this amazing story! Check out the paper at Nature Communications and the 🧵 by @nckvalerie.bsky.social below 👇. We believe #CeTeam will be an invaluable tool for #drugdiscovery and #targetvalidation in #cells

🔗: www.nature.com/articles/s41...
December 11, 2024 at 7:20 PM
nckvalerie.bsky.social
Good timing for a first Bluesky post! 🦋

I'm thrilled to share that our BioRxiv preprint on #CeTEAM has now been published in Nature Communications!

🔗: www.nature.com/articles/s41...

A short 🧵 1/x 👇
Coupling cellular drug-target engagement to downstream pharmacology with CeTEAM - Nature Communications
Cellular target engagement technologies enable quantification of intracellular drug binding, but the simultaneous assessment of drug-associated phenotypes is challenging. Here, the authors develop CeT...
www.nature.com
December 11, 2024 at 12:04 AM
Reposted by Nick Valerie
micharapelab.bsky.social
Excited to reveal specific reactive oxygen species as sentinel molecules that control localized protein degradation at #mitochondria to adjust electron transport chain abundance, with many implications for the role of ROS in development and disease.

www.cell.com/molecular-ce...
Reactive oxygen species control protein degradation at the mitochondrial import gate
This work identifies reactive oxygen species released by the electron transport chain as sentinel molecules that regulate localized protein degradation at mitochondrial TOM complexes, a mechanism that controls mitochondrial protein import and adjusts the abundance of the electron transport chain to cellular needs.
www.cell.com
December 6, 2024 at 7:07 AM
Reposted by Nick Valerie
aliceyting.bsky.social
Could one envision a synthetic receptor technology that is fully programmable, able to detect diverse extracellular antigens – both soluble and cell-attached – and convert that recognition into a wide range of intracellular responses, from gene expression and real-time fluorescence to modulation..
December 4, 2024 at 4:05 PM
Reposted by Nick Valerie
tat1anamoiseeva.bsky.social
Awesome paper, I think the authors are not on Bluesky yet
Multiple mechanisms for licensing human replication origins
Nature - Biochemical and structural studies of the loading pathway of the human MCM2–7 replicative helicase motor reveal differences from the orthologous yeast system that may increase...
www.nature.com
December 4, 2024 at 2:39 AM
Reposted by Nick Valerie
micharapelab.bsky.social
Very excited to present the structural and mechanistic basis for stress response silencing by the monster E3 ligase SIFI.

www.biorxiv.org/content/10.1...
December 3, 2024 at 7:05 AM
Reposted by Nick Valerie
mgarnett.bsky.social
Excited to launch a new Gordon Research Conference on synthetic lethality in oncology. Great cutting edge program, superb speakers and lots of networking opportunities. Applications open.
www.grc.org/synthetic-le...
2025 Synthetic Lethality Approaches in Oncology Conference GRC
The 2025 Gordon Research Conference on Synthetic Lethality Approaches in Oncology will be held in Portland, Maine. Apply today to reserve your spot.
www.grc.org
November 27, 2024 at 8:20 PM
Reposted by Nick Valerie
stephanhacker2.bsky.social
@thornsesholdlab.bsky.social set up a feed, that will show all posts with #ChemBio. If you are interested in the feed, click this link, click "Pin to Home" and it will be added as feed to your home screen:
bsky.app/profile/did...
I will use this hashtag in all relevant posts.
November 25, 2024 at 4:00 PM
Reposted by Nick Valerie
michaelnadbio.bsky.social
Intriguing new paper by @mflangelier.bsky.social in the Pascal lab showing that PARP1 can generate free poly-ADP-ribose (PAR) (not attached to proteins) in vitro and in cells. In some cases PAR is attached to NAD+! #PARP #ADP-ribosylation #NAD+

www.cell.com/molecular-ce...
PARP enzyme de novo synthesis of protein-free poly(ADP-ribose)
Langelier et al. discover that PARP1, PARP2, and Tankyrase catalyze de novo synthesis of protein-free poly(ADP-ribose), or PAR, in addition to canonical protein-linked PAR. Cellular free PAR did not r...
www.cell.com
November 20, 2024 at 7:15 PM
Reposted by Nick Valerie
thornsesholdlab.bsky.social
📯📯 Chemical Biology starter pack 📯📯
140 PIs & groups posting primary research in chemical biology.

Please reskeet (?) & reply to this post if you want to be added!
go.bsky.app/KLrTWoj

Let's make ChemBioSky even greater again!

#realtimechem #FluorescenceFriday #chemsky #chemtwitter #AgentOrange
November 17, 2024 at 10:58 PM
Reposted by Nick Valerie
pedroorteg.bsky.social
🧬 I'm happy to announce that our latest study, "ATR safeguards replication forks against APOBEC3B-induced toxic PARP1 trapping," is now available on bioRxiv! 🧬 Check it out here: biorxiv.org/content/10.1...

@buissonlab.bsky.social
ATR safeguards replication forks against APOBEC3B-induced toxic PARP1 trapping
ATR is the master safeguard of genomic integrity during DNA replication. Acute inhibition of ATR with ATR inhibitor (ATRi) triggers a surge in origin firing, leading to increased levels of single-stra...
biorxiv.org
November 16, 2024 at 5:05 PM