Philipp Niethammer

Have you ever wondered 🤔... Does phenotypic variance respond to environmental perturbation? Does it have a genetic basis? Are mean and variance regulating loci exposed to different selection pressures? These and more questions are explored in our new preprint 🔥

www.biorxiv.org/content/10.6...

Native chromatome profiling reveals hundreds of metabolic enzymes in the nucleus across tissues - Nature Communications Here proteomic chromatome analysis shows metabolic enzymes widely localize to chromatin in cancer in a tissue-specific manner. Nuclear enzymes affect DNA damage/repair and transcription, revealing non...

New paper out in Nature Communications:
www.nature.com/articles/s41...
We found >250 metabolic enzymes on chromatin.
Only ~20 had been reported before.
This means hundreds of metabolic enzymes may have unexplored nuclear roles.

Awesome speakers!

Zebrafish macrophages convert physical wound signals into rapid vascular permeabilization - Nature Communications Real-time imaging in zebrafish shows that macrophages convert fast osmotic wound signals into rapid vessel permeabilization via cPla2-dependent nuclear membrane mechanotransduction.

This is also true for zebrafish macrophages that sense osmotic shock waves coming wounds to nearby permeabilize blood vessels. www.nature.com/articles/s41...

So, its only with their ❤️nucleus❤️ that cells can see rightly.

And Shirin Bahmanyar's lab systematically investigated this here: www.biorxiv.org/content/10.1...

Endoplasmic reticulum disruption stimulates nuclear membrane mechanotransduction - Nature Cell Biology Shen, Gelashvili and Niethammer developed an inner nuclear membrane tension sensor and demonstrated that ER–nuclear membrane contiguity acts as a mechanical buffer.

We have previously exploited the convergence of both tension and curvature on membrane lipid packing in the opposite direction: We used the curvature sensing motif of ARFGAP1 to measure nuclear membrane tension upon ER disruption to show that the ER buffers tension. www.nature.com/articles/s41...

cPLA2α targeting to exosomes connects nuclear deformation to LTB4-signaling during neutrophil chemotaxis Nuclear squeezing triggers lipid signals that help neutrophils stay on course through tight spaces.

Another interesting example of how cPLA2 senses nuclear deformation and controls immune cell behaviour. Since the enzyme adsorbs to hydrophobic lipid packing defects, membrane tension and high positive curvature can have similar effects as membrane tension.
www.science.org/doi/10.1126/...

Finally, the final version 😀
www.nature.com/articles/s41...

And here some follow-up work from colleagues on our initial findings. Perhaps, what is still missing are direct measurements of electrical wound fields in zebrafish under different ion/osmolyte treatments, e.g., using a vibrating probe. elifesciences.org/articles/62386

And here some follow-up work from colleagues on our initial findings. Perhaps, what is still missing are direct measurements of electrical wound fields in zebrafish under different ion/osmolyte treatments, e.g., using a vibrating probe.

How do different ions affect rapid vessel leakage and wound closure after injury? Iv measures vessel leakage. Ib measures rapid wound closure. ISO*: non-NaCl isotonic treatments. Consider the ISO vs. ISO* difference - evidence for electric wound fields or sth. else???
www.nature.com/articles/s41...

"Amphipathic helices sense the inner nuclear membrane environment through lipid packing defects"
www.biorxiv.org/content/10.1...

Zaza’s main PhD work just came out in a journal! Macrophage cell nuclei physically sense 50 um/s fast osmotic shock waves coming from wounds to mediate rapid vessel permeabilization and serum exudation - one of the hallmarks of acute inflammation. www.nature.com/articles/s41...

Excited to join the Editorial Board of @plosbiology.org, one of the pioneers of high-quality, open-access publishing.

Calcium waves and nuclear tension changes coordinate mechanical stress dissipation in locally folded epithelia Cell biology; Mechanobiology

Calcium waves and nuclear tension changes coordinate mechanical stress dissipation in locally folded epithelia: iScience www.cell.com/iscience/ful...

β2-Integrins regulate dendritic cells through nuclear deformation and activation of phospholipase A2 and DNA damage–inducible GADD34 Dendritic cells (DCs) reside in tissues and are activated by danger or pathogen-associated signals, leading to expression of costimulatory markers and cytokines, downregulation of β2-integrin–mediated...

β2-Integrins regulate dendritic cells through nuclear deformation and activation of phospholipase A2 and DNA damage–inducible GADD34 - Journal of Biological Chemistry www.jbc.org/article/S002...

2) Discovery of 5-oxoETE as a novel mucosal resilience signal. Both studies are currently under re-review (3/3). www.biorxiv.org/content/10.1...

1) Discovery of a missing link between cellular redox state and acute inflammation (2/3).
www.biorxiv.org/content/10.1...

Looking forward to presenting two exciting discoveries made by Yanan Ma and Miklos Lengyel on the role of metabolic redox signaling for epithelial defense and resilience on the European Phagocyte Workshop in Oxford in March (1/3).
www.phagocytes2026.com

Curved Microfluidic Confinement Reveals Cell-Shape-Dependent Nuclear Mechanotransduction in Adaptive Migration Cells navigate within diverse curved microenvironments derived from extracellular matrix (ECM) and neighboring cells in vivo. While current studies primarily focus on cell migration on curved surfaces...

Cells navigating microscale curved environments stretch their nuclei, triggering the membrane stretch-sensitive cPLA2 pathway, which in turn rewires cell signaling and morphodynamics to propel the cell forward and avoid steric hindrance pubs.acs.org/doi/10.1021/...

zenodo.org/records/1832...

So, when most papers, grants along with their reviews, are generated, i.e, with a ~ 5-20% chance hallucinated, by AI, we PIs can finally retreat into our thermal harvesting pods to generate the electricity for the server plants that power the AI? Wait, what does this remind me of…? 🤔

LCS v2.9 user interface. Load different sGCA or sGEA sheets via the Build network button to generate "syntactic" (gene name overlap) or "semantic" (functional association overlap) networks, respectively.

Semantic network of overlapping functional gene associations

Latest LCS update: Besides generating 'syntactic overlap networks' from different sGCA sheets, the 'Build network' button now also integrates different sGEA sheets (functional associations) into a 'semantic overlap network'. Just load sGEA- instead of sGCA-sheets.
github.com/niethamp/Log...

Happy New Year everybody!

Perivascular Macrophages Convert Physical Wound Signals Into Rapid Vascular Responses Leukocytes detect distant wounds within seconds to minutes, which is essential for effective pathogen defense, tissue healing, and regeneration. Blood vessels must detect distant wounds just as rapidl...

A substantially revised version of Zaza's outstanding PhD work is accepted (in principle) at Nature Communications. Many thanks to the reviewers and editor for their constructive comments and guidance!
www.biorxiv.org/content/10.1...

bsky.app/profile/niet...

Mechanotransduction by nuclear envelope tension Mechanotransduction mediated by the tension in lipid membranes is a well-established paradigm. This has been studied largely in the context of the plasma membrane, but recent work shows that it app...

This review was a fun collaboration with
Pere Roca-Cusachs - just published in a journal! www.tandfonline.com/doi/full/10....