Bernadette Freeman

• PhD
• Project Manager at Alfred Hospital

COPD is a major cause of global mortality and morbidity but current treatments are poorly effective. This is because the underlying mechanisms that drive the development and progression of COPD are incompletely understood. Animal models of disease provide a valuable, ethically and economically viable experimental platform to examine these mechanism...

Microbes or danger signals trigger inflammasome sensors, which induce polymerization of the adaptor ASC and the assembly of ASC specks. ASC specks recruit and activate caspase-1, which induces maturation of the cytokine interleukin 1β (IL-1β) and pyroptotic cell death. Here we found that after pyroptosis, ASC specks accumulated in the extracellular...

Background: Severe steroid-insensitive asthma is a substantial clinical problem. Effective treatments are urgently required, however, their development is hampered by a lack of understanding of the mechanisms of disease pathogenesis. Steroid-insensitive asthma is associated with respiratory tract infections and noneosinophilic endotypes, including...

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

Objective: Increased inflammasome responses are strongly implicated in inflammatory diseases; however, their specific roles are incompletely understood. Therefore, we sought to examine the roles of NLRP3 and AIM2 inflammasomes in cigarette smoke-induced inflammation in a model of experimental chronic obstructive pulmonary disease (COPD). Methods:...

Background and objective Chronic obstructive pulmonary disease (COPD) is the third leading cause of illness and death worldwide. Current treatments aim to control symptoms with none able to reverse disease or stop its progression. We explored the major molecular changes in COPD pathogenesis. Methods We employed quantitative label-based proteomics...

Rationale: Necroptosis, mediated by RIPK3 and MLKL, is a form of regulated necrosis that can drive tissue inflammation and destruction, however its contribution to COPD pathogenesis is poorly understood. Objectives: To determine the role of necroptosis in COPD. Methods: Levels of RIPK3, MLKL and activated phospho-MLKL were measured in lung tis...

The urinary tract consists of the bladder, ureters, and kidneys, and is an essential organ system for filtration and excretion of waste products and maintaining systemic homeostasis. In this capacity, the urinary tract is impacted by its interactions with other mucosal sites, including the genitourinary and gastrointestinal systems. Each of these s...

Purpose: This systematic review evaluates the current intervention strategies for cystinuria and assesses their quality and efficacy in order to determine the need to identify new and improved strategies for treatment. Materials and Methods: A literature search for interventions in cystinuria was conducted on key electronic databases for studies pu...

Bronchioalveolar stem cells (BASCs) are a lung resident stem cell population located at bronchioalveolar duct junctions that contribute to the maintenance of bronchiolar club cells and alveolar epithelial cells of the distal lung. Their transformed counterparts are considered to be likely progenitors of lung adenocarcinomas, which has been a major...

Increased iron levels and/or dysregulated iron homeostasis occurs in several lung diseases. Here, the effects of iron accumulation on the pathogenesis of pulmonary fibrosis and associated lung function decline was investigated using a combination of murine models of iron overload and bleomycin-induced pulmonary fibrosis, primary human lung fibrobla...

Tissue remodeling/fibrosis is a major feature of all fibrotic diseases, including idiopathic pulmonary fibrosis (IPF). It is underpinned by accumulating extracellular matrix (ECM) proteins. Fibulin-1c (Fbln1c) is a matricellular ECM protein associated with lung fibrosis in both humans and mice, and stabilizes collagen formation. Here we discovered...

Supplementary Fig. 2: T‐bet+ ILC1s and Rorγt+ ILC3s are increased and GATA3+ ILC2s are decreased in WT mice exposed to CS. Flow cytometric analysis of single cell suspensions from whole lungs of normal air‐ or CS‐exposed WT mice. (A) Flow cytometry gating of ILC1s, ILC2s and ILC3s. Quantification of (B) total ILCs, (C) ILC1s, (D) ILC2s, and (E) ILC...

Supplementary Fig. 1: Top 5 differentially expressed genes identified from RT2 ECM PCR array in WT, Rag1−/− and Rorafl/flIL7RCre mice exposed to CS. Relative abundance of the top 5 genes compared to the geometric mean of Actb, B2m, Gapdh, for normal air‐ and CS‐exposed A) Rag1−/− mice and B) Rorafl/flIL7RCre mice compared to WT controls. cDNA was p...

Chronic obstructive pulmonary disease (COPD) and lung cancer are major lung diseases affecting millions worldwide. Both diseases have links to cigarette smoking and exert a considerable societal burden. People suffering from COPD are at higher risk of developing lung cancer than those without, and are more susceptible to poor outcomes after diagnos...

Pulmonary inflammation in chronic obstructive pulmonary disease (COPD) is characterized by both innate and adaptive immune responses; however, their specific roles in the pathogenesis of COPD are unclear. Therefore, we investigated the roles of T and B lymphocytes and group 2 innate lymphoid cells (ILC2s) in airway inflammation and remodelling, and...

Crohn's disease (CD) is a chronic inflammatory disease of the gastrointestinal tract (GIT). Cigarette smoke (CS) exposure and chronic obstructive pulmonary disease (COPD) are risk factors for CD, although the mechanisms involved are poorly understood. We employed a mouse model of CS-induced experimental COPD and clinical studies to examine these me...

Introduction The airway epithelium is a physical and immunological barrier that protects the pulmonary system from inhaled environmental insults. Uric acid has been detected in the respiratory tract and can function as an antioxidant or damage associated molecular pattern. We have demonstrated that human airway epithelial cells are a source of uric...

IL-6 does not elevate extracellular uric acid levels or XDH gene expression in HBEC-6KT human airway epithelial cells. Human airway epithelial cells were exposed to recombinant human IL-6 (100ng/ml) for 24h followed by analysis of (A) cell culture supernatant uric acid levels and (B) XDH gene expression. Data represent mean +/- SD, n = 3. Significa...

EGF does not elevate extracellular uric acid levels or XDH gene expression in HBEC-6KT human airway epithelial cells. Human airway epithelial cells were exposed to increasing concentrations of EGF or HDM in culture for 24h followed by analysis of (A) cell culture supernatant uric acid levels and (B) XDH gene expression. Data represent mean +/- SD,...

Excel file of all raw data used for figures and analysis. (XLSX)

Introduction: Steroid-insensitive (SI) asthma is of considerable clinical and economic significance and improved therapies are urgently required, however, the development of therapies has been hampered by a lack of understanding of the processes that underpin disease. Aim: To develop experimental models of SI asthma that represent different subtype...

BACKGROUND: Severe, steroid-insensitive (SSI) asthma is a substantial clinical problem. Effective treatments are urgently required, however, their development is hampered by a lack of understanding of the mechanisms that promote disease. SSI asthma is associated with respiratory infections and non-eosinophilic endotypes of disease, including neutro...

Microbes or danger signals trigger inflammasome sensors, which induce polymerization of the adaptor ASC and the assembly of ASC specks. ASC specks recruit and activate caspase-1, which induces maturation of the cytokine interleukin 1β (IL-1β) and pyroptotic cell death. Here we found that after pyroptosis, ASC specks accumulated in the extracellular...