Biology subjects

Salner, A.

Publications and source records attributed to Salner, A..

3 recordsLinked to original sources

bioRxiv2025

Intron retention regulates STAT2 function and predicts immunotherapy response in lung cancer

Immunotherapy benefits only a subset of lung cancer patients, and the molecular determinants of variable outcomes remain unclear. Using long-read RNA-sequencing we mapped the landscape of alternative RNA splicing in human primary lung adenocarcinomas. We identified over 180,000 full-length mRNA isoforms, more than half of which were novel and many of which occurred in immune-related genes, particularly within the type I interferon response pathway. We discovered retained introns in the STAT2 gene that produce altered protein isoforms that regulate immune signaling and interferon responses. Furthermore, STAT2 intron retention levels predicted patient responses to checkpoint inhibitors. These findings position alternative splicing as a key regulator of tumor immune responses and reveal mRNA splicing alterations as potential biomarkers to identify patients who might respond to cancer immunotherapy.

immunology↗

bioRxiv2023

Species- and strain-effects in interferon, innate immunity, and barrier transcriptional response of microbiome interactions of 3D respiratory epithelial cultures

The microbiome modulates the respiratory epitheliums immunomodulatory functions. To explore how the microbiomes biodiversity affects microbe-epithelial interactions, we screened 58 phylogenetically diverse microbes for their transcriptomic effect on tracheobronchial air-liquid interface cell (ALI) cultures. We found distinct species- and strain-level differences in host innate immunity, and epithelial barrier response. Strikingly, we found that host interferon, an antiviral immune response, was one of the most variable host processes, and this variability was not driven by microbial phylogenetic diversity, bioburden, nor by the microbes ability to stimulate other innate immunity pathways. Our study provides a foundation for understanding how the respiratory microbiomes biodiversity affects epithelial, and particularly, antiviral innate immunity.

microbiology↗

bioRxiv2023

Spatiotemporally organized immunomodulatory response to SARS-CoV-2 virus in primary human broncho-alveolar epithelia

The COVID-19 pandemic continues to be a health crisis with major unmet medical needs. The early responses from airway epithelial cells, the first target of the virus regulating the progression towards severe disease, are not fully understood. Primary human air-liquid interface cultures representing the broncho-alveolar epithelia were used to study the kinetics and dynamics of SARS-CoV-2 variants infection. The infection measured by nucleoprotein expression, was a late event appearing between day 4-6 post infection for Wuhan-like virus. Other variants demonstrated increasingly accelerated timelines of infection. All variants triggered similar transcriptional signatures, an "early" inflammatory/immune signature preceding a "late" type I/III IFN, but differences in the quality and kinetics were found, consistent with the timing of nucleoprotein expression. Response to virus was spatially organized: CSF3 expression in basal cells and CCL20 in apical cells. Thus, SARS-CoV-2 virus triggers specific responses modulated over time to engage different arms of immune response.

immunology↗