Publications

IL-22 resolves MASLD via enterocyte STAT3 restoration of diet-perturbed intestinal homeostasis

Peng Zhang et al.

Cell Metab. 2024 Oct 1;36(10):2341-2354.e6. doi: 10.1016/j.cmet.2024.08.012. Epub 2024 Sep 23.

The exponential rise in metabolic dysfunction-associated steatotic liver disease (MASLD) parallels the ever-increasing consumption of energy-dense diets, underscoring the need for effective MASLD-resolving drugs. MASLD pathogenesis is linked to obesity, diabetes, "gut-liver axis" alterations, and defective interleukin-22 (IL-22) signaling. Although barrier-protective IL-22 blunts diet-induced metabolic alterations, inhibits lipid intake, and reverses microbial dysbiosis, obesogenic diets rapidly...

Atomistic simulations reveal impacts of missense mutations on the structure and function of SynGAP1

Aliaa E Ali et al.

Brief Bioinform. 2024 Sep 23;25(6):bbae458. doi: 10.1093/bib/bbae458.

De novo mutations in the synaptic GTPase activating protein (SynGAP) are associated with neurological disorders like intellectual disability, epilepsy, and autism. SynGAP is also implicated in Alzheimer's disease and cancer. Although pathogenic variants are highly penetrant in neurodevelopmental conditions, a substantial number of them are caused by missense mutations that are difficult to diagnose. Hence, in silico mutagenesis was performed for probing the missense effects within the N-terminal...

Single-cell transcriptome analysis of the early immune response in the lymph nodes of Borrelia burgdorferi-infected mice

Varpu Rinne et al.

Microbes Infect. 2025 Feb;27(2):105424. doi: 10.1016/j.micinf.2024.105424. Epub 2024 Sep 19.

Lyme borreliosis is a disease caused by Borrelia burgdorferi sensu lato bacteria. Borrelia burgdorferi is known to induce prolonged extrafollicular immune responses and abnormal germinal centre formation. The infection fails to generate a neutralizing type of immunity, eventually establishing a persistent infection. Here, we performed single-cell RNA sequencing to characterize the immune landscape of lymph node lymphocytes during the early Borrelia burgdorferi infection in a murine model. Our...

Proteomic profiling identifies a direct interaction between heat shock transcription factor 2 and the focal adhesion adapter talin-1

Alejandro J Da Silva et al.

FEBS J. 2024 Nov;291(21):4830-4848. doi: 10.1111/febs.17271. Epub 2024 Sep 16.

Heat shock factor 2 (HSF2) is a versatile transcription factor that regulates gene expression under stress conditions, during development, and in disease. Despite recent advances in characterizing HSF2-dependent target genes, little is known about the protein networks associated with this transcription factor. In this study, we performed co-immunoprecipitation coupled with mass spectrometry analysis to identify the HSF2 interactome in mouse testes, where HSF2 is required for normal sperm...

Heat stress sensitizes zebrafish embryos to neurological and cardiac toxicity

Anna-Mari Haapanen-Saaristo et al.

Biochem Biophys Res Commun. 2024 Nov 12;733:150682. doi: 10.1016/j.bbrc.2024.150682. Epub 2024 Sep 10.

Global warming increases the risk of dangerous heat waves, which may have deleterious effects on humans and wildlife. Here, we have utilized zebrafish embryos as a model to analyze heat stress and effect of chemical compounds on responses to heat stress. The temperature adaptation limit of zebrafish embryos was 37 °C in behavioural test and 38 °C in cardiac test. Polyaromatic hydrocarbon phenanthrene completely blocked the behavioural adaptation to heat stress. Interestingly, the cardiotoxic...

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...