Publications

Although best known for their involvement in modulating nociception, Neuropeptide FF (NPFF) group peptides have been suggested to fulfil a variety of biological functions such as feeding, anxiety behaviors and thermogenesis. However, evidence supporting these functions of NPFF is mostly pharmacological, leaving the physiological relevance unaddressed. Here we examined the physiological impact of lack of NPFF signalling in both genders using a Npff-/- mouse model.

Cellular interactions between endothelial cells and macrophages regulate macrophage localization and phenotype, but the mechanisms underlying these interactions are poorly understood. Here we explored the role of sialoglycans on lymphatic endothelial cells (LEC) in interactions with macrophage-expressed Siglec-1 (CD169). Lectin-binding assays and mass spectrometric analyses revealed that LEC from human skin express more sialylated glycans than the corresponding blood endothelial cells.

Nonalcoholic fatty liver disease (NAFLD) is a global health-care problem with limited therapeutic options. To obtain a cellular resolution of pathogenesis, 82,168 single-cell transcriptomes (scRNA-seq) across different NAFLD stages were profiled, identifying hepatocytes and 12 other non-parenchymal cell (NPC) types. scRNA-seq revealed insights into the cellular and molecular mechanisms of the disease. We discovered a dual role for hepatic stellate cells in gene expression regulation and in the potential to trans-differentiate into myofibroblasts.

Nonconvulsive epileptiform activity and microglial alterations have been detected in people with Alzheimer’s disease (AD) and related mouse models. However, the relationship between these abnormalities remains to be elucidated. We suppressed epileptiform activity by treatment with the antiepileptic drug levetiracetam or by genetic ablation of tau and found that these interventions reversed or prevented aberrant microglial gene expression in brain tissues of aged human amyloid precursor protein transgenic mice, which simulate several key aspects of AD.

Fibrosis-driven solid organ failure is an enormous burden on global health. Spiny mice (Acomys) are terrestrial mammals that can regenerate severe skin wounds without scars to avoid predation. Whether spiny mice also regenerate internal organ injuries is unknown. Here, we show that despite equivalent acute obstructive or ischemic kidney injury, spiny mice fully regenerate nephron structure and organ function without fibrosis, whereas C57Bl/6 or CD1 mice progress to complete organ failure with extensive renal fibrosis.

Both preclinical and clinical studies have demonstrated that exposures to acetaminophen (APAP) at levels that cause hepatic injury cause pulmonary injury as well. However, whether exposures that do not result in hepatic injury have acute pulmonary implications is unknown. Thus, we sought to determine how APAP exposures at levels that do not result in significant hepatic injury impact the mature lung.

Epithelial-mesenchymal transition (EMT) creates an environment facilitating fibrosis following alveolar epithelial cell injury. IL-23 has important roles in chronic autoimmune conditions like rheumatoid arthritis (RA), but its role in the interstitial lung disease that affects RA patients is unclear. This study aimed to determine the pro-fibrogenic role of IL-23 on somatic alveolar type I (ATI) epithelial cells. Primary ATI cells were isolated from rats and cultured on plastic dishes for 1-3 weeks.

Background: People with CF are at risk for malnutrition and fat-soluble vitamin deficiencies due to pancreatic insufficiency and fat malabsorption. Highly effective CFTR modulators, ivacaftor and elexacaftor/tezacaftor/ ivacaftor, substantially improve CFTR activity, lung function and nutritional status (weight and body mass index) in people with CF with certain genetic mutations [1, 2]. Fat-soluble vitamin levels (vitamins A, D, and E) are assessed annually in children with CF.

Background: Mucus buildup in multiple mucin-producing organs, including the lungs and the intestine, is the hallmark of CF. In the gastrointestinal (GI) tract, aberrant mucus properties may play a critical role in bowel obstruction, inflammation, and bacterial overgrowth, as well as reduced nutrient absorption. Interestingly, all animal models of CF (e.g., mice, rats, ferrets, pigs) experience gastrointestinal complications, with poor growth and intestinal obstruction, as a result of excessive mucus accumulation.

Background: Malnutrition has historically been a main clinical consequence of CF. Consensus recommendations have encouraged a highcalorie, high-fat diet but with little guidance related to nutrient density or quality of foods consumed to meet elevated metabolic needs. Highly effective modulators are associated with improved growth and increases in weight and body mass index (BMI) in subsets of the CF population. Recently elexacaftor/tezacaftor/ivacaftor was approved for use in up to 90% of people with CF.