Publications

SHANK3 depletion leads to ERK signalling overdose and cell death in KRAS-mutant cancers

Johanna Lilja et al.

Nat Commun. 2024 Sep 12;15(1):8002. doi: 10.1038/s41467-024-52326-1.

The KRAS oncogene drives many common and highly fatal malignancies. These include pancreatic, lung, and colorectal cancer, where various activating KRAS mutations have made the development of KRAS inhibitors difficult. Here we identify the scaffold protein SH3 and multiple ankyrin repeat domain 3 (SHANK3) as a RAS interactor that binds active KRAS, including mutant forms, competes with RAF and limits oncogenic KRAS downstream signalling, maintaining mitogen-activated protein kinase/extracellular...

Phenotypic profiling of human induced regulatory T cells at early differentiation: insights into distinct immunosuppressive potential

Roosa Kattelus et al.

Cell Mol Life Sci. 2024 Sep 12;81(1):399. doi: 10.1007/s00018-024-05429-3.

Regulatory T cells (Tregs) play a key role in suppressing systemic effector immune responses, thereby preventing autoimmune diseases but also potentially contributing to tumor progression. Thus, there is great interest in clinically manipulating Tregs, but the precise mechanisms governing in vitro-induced Treg (iTreg) differentiation are not yet fully understood. Here, we used multiparametric mass cytometry to phenotypically profile human iTregs during the early stages of in vitro...

Comparative proteomics analysis of the mouse mini-gut organoid: insights into markers of gluten challenge from celiac disease intestinal biopsies

Robert Moulder et al.

Front Mol Biosci. 2024 Aug 28;11:1446822. doi: 10.3389/fmolb.2024.1446822. eCollection 2024.

INTRODUCTION: Organoid models enable three-dimensional representation of cellular systems, providing flexible and accessible research tools, and can highlight key biomolecules. Such models of the intestinal epithelium can provide significant knowledge for the study of celiac disease and provide an additional context for the nature of markers observed from patient biopsy data.

Hypoxia and Foxn1 alter the proteomic signature of dermal fibroblasts to redirect scarless wound healing to scar-forming skin wound healing in Foxn1-/- mice

Barbara Gawronska-Kozak et al.

BMC Biol. 2024 Sep 11;22(1):193. doi: 10.1186/s12915-024-01990-2.

CONCLUSIONS: The present data highlight the effect of hypoxia and Foxn1 on the protein profile and functionality of regenerative Foxn1^(-/-) DFs and demonstrate that the introduction of Foxn1 and Hif-1α into the wounded skin of regenerative Foxn1^(-/-) mice activates reparative/scar-forming healing.

Serum lipidome associates with neuroimaging features in patients with traumatic brain injury

Ilias Thomas et al.

iScience. 2024 Aug 3;27(9):110654. doi: 10.1016/j.isci.2024.110654. eCollection 2024 Sep 20.

Acute traumatic brain injury (TBI) is associated with substantial abnormalities in lipid biology, including changes in the structural lipids that are present in the myelin in the brain. We investigated the relationship between traumatic microstructural changes in white matter from magnetic resonance imaging (MRI) and quantitative lipidomic changes from blood serum. The study cohort included 103 patients from the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) study....

Disruption of HSD17B12 in mouse hepatocytes leads to reduced body weight and defect in the lipid droplet expansion associated with microvesicular steatosis

Hanna Heikelä et al.

FASEB J. 2024 Sep 15;38(17):e70034. doi: 10.1096/fj.202400333RR.

The function of hydroxysteroid dehydrogenase 12 (HSD17B12) in lipid metabolism is poorly understood. To study this further, we created mice with hepatocyte-specific knockout of HSD17B12 (LiB12cKO). From 2 months on, these mice showed significant fat accumulation in their liver. As they aged, they also had a reduced whole-body fat percentage. Interestingly, the liver fat accumulation did not result in the typical formation of large lipid droplets (LD); instead, small droplets were more prevalent....