Publications

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...

SNM1A is crucial for efficient repair of complex DNA breaks in human cells

Lonnie P Swift et al.

Nat Commun. 2024 Jun 25;15(1):5392. doi: 10.1038/s41467-024-49583-5.

DNA double-strand breaks (DSBs), such as those produced by radiation and radiomimetics, are amongst the most toxic forms of cellular damage, in part because they involve extensive oxidative modifications at the break termini. Prior to completion of DSB repair, the chemically modified termini must be removed. Various DNA processing enzymes have been implicated in the processing of these dirty ends, but molecular knowledge of this process is limited. Here, we demonstrate a role for the...

Wnt/β-catenin-YAP axis in the pathogenesis of primary intraosseous carcinoma NOS, deriving from odontogenic keratocyst

Yusuke Nakako et al.

Pathol Res Pract. 2024 Aug;260:155420. doi: 10.1016/j.prp.2024.155420. Epub 2024 Jun 20.

Odontogenic tumors (OGTs), which originate from cells of odontogenic apparatus and their remnants, are rare entities. Primary intraosseous carcinoma NOS (PIOC), is one of the OGTs, but it is even rarer and has a worse prognosis. The precise characteristics of PIOC, especially in immunohistochemical features and its pathogenesis, remain unclear. We characterized a case of PIOC arising from the left mandible, in which histopathological findings showed a transition from the odontogenic keratocyst...