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Mapping the landscape of chromatin dynamics during naïve CD4+ T-cell activation

T-cell activation induces context-specific gene expression programs that promote energy generation and biosynthesis, progression through the cell cycle and ultimately cell differentiation. The aim of this study was to apply the omni ATAC-seq method to characterize the landscape of chromatin changes induced by T-cell activation in mature naïve CD4+ T-cells.

PPARalpha and PPARgamma activation is associated with pleural mesothelioma invasion but therapeutic inhibition is ineffective

Mesothelioma is a cancer that typically originates in the pleura of the lungs. It rapidly invades the surrounding tissues, causing pain and shortness of breath. We compared cell lines injected either subcutaneously or intrapleurally and found that only the latter resulted in invasive and rapid growth.

Fine-Tuning the Tumour Microenvironment: Current Perspectives on the Mechanisms of Tumour Immunosuppression

Immunotherapy has revolutionised the treatment of cancers by harnessing the power of the immune system to eradicate malignant tissue. However, it is well recognised that some cancers are highly resistant to these therapies, which is in part attributed to the immunosuppressive landscape of the tumour microenvironment (TME). The contexture of the TME is highly heterogeneous and contains a complex architecture of immune, stromal, vascular and tumour cells in addition to acellular components such as the extracellular matrix. While understanding the dynamics of the TME has been instrumental in predicting durable responses to immunotherapy and developing new treatment strategies, recent evidence challenges the fundamental paradigms of how tumours can effectively subvert immunosurveillance. Here, we discuss the various immunosuppressive features of the TME and how fine-tuning these mechanisms, rather than ablating them completely, may result in a more comprehensive and balanced anti-tumour response.

Decoding Susceptibility to Respiratory Viral Infections and Asthma Inception in Children

Human Respiratory Syncytial Virus and Human Rhinovirus are the most frequent cause of respiratory tract infections in infants and children and are major triggers of acute viral bronchiolitis, wheezing and asthma exacerbations.

Assessing the unified airway hypothesis in children via transcriptional profiling of the airway epithelium

Upper and lower airways are conserved in their transcriptional composition, and variations associated with disease are present in both nasal and tracheal epithelium

Using Systems Biology to understand asthma exacerbations and develop better treatments

Alexander Anthony Deborah Pat Larcombe Kicic Strickland Holt BScEnv (Hons) PhD BSc (Hons) PhD PhD PhD, DSc, FRCPath, FRCPI, FAA Honorary Research

Geldanamycin treatment does not result in anti-cancer activity in a preclinical model of orthotopic mesothelioma

Mesothelioma is characterised by its aggressive invasive behaviour, affecting the surrounding tissues of the pleura or peritoneum. We compared an invasive pleural model with a non-invasive subcutaneous model of mesothelioma and performed transcriptomic analyses on the tumour samples.

Airway and parenchymal transcriptomics in a novel model of asthma and COPD overlap

Asthma and chronic obstructive pulmonary disease (COPD) are common chronic respiratory diseases, and some patients have overlapping disease features, termed asthma-COPD overlap. Patients characterized with ACO have increased disease severity; however, the mechanisms driving this have not been widely studied.

Off-target effects of bacillus Calmette-Guerin vaccination on immune responses to SARS-CoV-2: implications for protection against severe COVID-19

Because of its beneficial off-target effects against non-mycobacterial infectious diseases, bacillus Calmette-Guérin vaccination might be an accessible early intervention to boost protection against novel pathogens. Multiple epidemiological studies and randomised controlled trials are investigating the protective effect of BCG against coronavirus disease 2019 (COVID-19).