Publications

Protocol to study early lung developmental branching in mouse embryos using explant culture

Salli Talvi et al.

STAR Protoc. 2024 Sep 20;5(3):103198. doi: 10.1016/j.xpro.2024.103198. Epub 2024 Jul 17.

Mouse lung branching morphogenesis creates epithelial tree structures required for respiration. Here, we present a protocol for studying mouse lung developmental branching using lung explant cultures. We describe steps for isolating lungs with a video at embryonic day 12.5 (E12.5) and culturing as an explant for 2 days. We also detail procedures for microscopic imaging on days 0-2 and analysis of peripheral lung buds. This technique has the potential to investigate lung development in various...

TLNRD1 is a CCM complex component and regulates endothelial barrier integrity

Neil J Ball et al.

J Cell Biol. 2024 Sep 2;223(9):e202310030. doi: 10.1083/jcb.202310030. Epub 2024 Jul 16.

We previously identified talin rod domain-containing protein 1 (TLNRD1) as a potent actin-bundling protein in vitro. Here, we report that TLNRD1 is expressed in the vasculature in vivo. Its depletion leads to vascular abnormalities in vivo and modulation of endothelial cell monolayer integrity in vitro. We demonstrate that TLNRD1 is a component of the cerebral cavernous malformations (CCM) complex through its direct interaction with CCM2, which is mediated by a hydrophobic C-terminal helix in...

Identification of an H-Ras nanocluster disrupting peptide

Candy Laura Steffen et al.

Commun Biol. 2024 Jul 9;7(1):837. doi: 10.1038/s42003-024-06523-9.

Hyperactive Ras signalling is found in most cancers. Ras proteins are only active in membrane nanoclusters, which are therefore potential drug targets. We previously showed that the nanocluster scaffold galectin-1 (Gal1) enhances H-Ras nanoclustering via direct interaction with the Ras binding domain (RBD) of Raf. Here, we establish that the B-Raf preference of Gal1 emerges from the divergence of the Raf RBDs at their proposed Gal1-binding interface. We then identify the L5UR peptide, which...

Body-wide genetic deficiency of poly(ADP-ribose) polymerase 14 sensitizes mice to colitis

Madhukar Vedantham et al.

FASEB J. 2024 Jul 15;38(13):e23775. doi: 10.1096/fj.202400484R.

Inflammatory bowel disease (IBD) is a chronic disease of the gastrointestinal tract affecting millions of people. Here, we investigated the expression and functions of poly(ADP-ribose) polymerase 14 (Parp14), an important regulatory protein in immune cells, with an IBD patient cohort as well as two mouse colitis models, that is, IBD-mimicking oral dextran sulfate sodium (DSS) exposure and oral Salmonella infection. Parp14 was expressed in the human colon by cells in the lamina propria, but, in...

Multi-omics analysis reveals drivers of loss of β-cell function after newly diagnosed autoimmune type 1 diabetes: An INNODIA multicenter study

Jose Juan Almagro Armenteros et al.

Diabetes Metab Res Rev. 2024 Jul;40(5):e3833. doi: 10.1002/dmrr.3833.

CONCLUSIONS: Features that differ between individuals with slow and rapid decline in β-cell mass could be valuable in staging and prediction of the rate of disease progression and thus enable smarter (shorter and smaller) trial designs for disease modifying therapies as well as offering biomarkers of therapeutic effect.

Cancer cell invasion alters the protein profile of extracellular vesicles

Jens C Luoto et al.

J Extracell Biol. 2023 Nov 27;2(12):e124. doi: 10.1002/jex2.124. eCollection 2023 Dec.

Extracellular vesicles (EVs) are important mediators of intercellular communication involved in local and long-range signalling of cancer metastasis. The onset of invasion is the key step of the metastatic cascade, but the secretion of EVs has remained unexplored at that stage due to technical challenges. In this study, we present a platform to track EVs over the course of invasive development of human prostate cancer cell (PC3) tumoroids utilizing in vivo-mimicking extracellular matrix-based 3D...