Catriona Kelly

Ulster University · Northern Ireland Centre for Stratified Medicine

Introduction: Cellular senescence is the irreversible growth arrest subsequent to oncogenic mutations, DNA damage, or metabolic insult. Senescence is associated with ageing and chronic age associated diseases such as cardiovascular disease and diabetes. The involvement of cellular senescence in acute kidney injury (AKI) and chronic kidney disease (...

Cellular senescence is the irreversible growth arrest subsequent to oncogenic mutations, DNA damage or metabolic insult. Senescence is associated with aging and chronic age associated diseases such as cardiovascular disease and diabetes. The involvement of cellular senescence in Acute Kidney Injury (AKI) and Chronic Kidney Disease (CKD) is not full...

TWEAK (tumor necrosis factor-like weak inducer of apoptosis) is a member of the TNF superfamily that controls a multitude of cellular events including proliferation, migration, differentiation, apoptosis, angiogenesis, and inflammation. TWEAK control of these events is via an expanding list of intracellular signalling pathways which include NF-κB,...

Introduction: Cardiovascular disease (CVD) is the leading cause of mortality in people with Type 2 diabetes mellitus (T2DM). Statins reduce low-density lipoproteins and positively affect CVD outcomes. Statin type and dose have differential effects on glycaemia and risk of incident T2DM; however, the impact of gender, and of individual drugs within...

The dysregulated immune system represents a major target for improving health outcomes in a range of chronic conditions. This chapter describes key changes in the immune system as we age and showcases its dysregulation across five chronic conditions including diabetes, cardiovascular disease, and cancer, highlighting dysregulated key immune system...

Vitamin D and cholesterol metabolism overlap significantly in the pathways that contribute to their biosynthesis. However, our understanding of their independent and co-regulation is limited. Cardiovascular disease is the leading cause of death globally and atherosclerosis, the pathology associated with elevated cholesterol, is the leading cause of...

TNFAIP3 encodes a zinc finger protein called A20, which has potent anti-inflammatory and anti-apoptotic properties. A20 promotes beta cell survival and protects against islet graft rejection in experimental models. The current study sought to investigate the mechanisms underlying the protective role of A20 in the pancreatic beta cell. Two islet cel...

GWAS studies have identified a number of SNPs connected to the development of type 1 diabetes (T1D). It is unclear how these variants confer risk for T1D development and whether this is based on direct effects on the beta cell, or whether the systemic inflammatory environment is detrimental to the beta cell. Using CRISPR mediated homology directed...

Background Type 1 Diabetes Mellitus (T1DM) is partly driven by autoimmune destruction of the pancreatic beta cell, facilitated by the release of inflammatory cytokines, including IFN-γ, TNF-α and IL-1β by cells of the innate immune system. Mesenchymal Stem Cells (MSCs) have been used to counteract autoimmunity in a range of therapeutic settings due...

Cystic fibrosis-related diabetes (CFRD) worsens CF lung disease leading to early mortality. Loss of beta cell area, even without overt diabetes or pancreatitis is consistently observed. We investigated whether short-term CFTR inhibition was sufficient to impact islet morphology and function in otherwise healthy mice. CFTR was inhibited in C57BL/6 m...

Cystic fibrosis–related diabetes (CFRD) is among the most common extrapulmonary co-morbidity associated with cystic fibrosis (CF), affecting an estimated 50% of adults with the condition. Cystic fibrosis is prevalent in 1 in every 2500 Caucasian live births and is caused by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR...

Central necrosis hampers the formation of highly biofunctional Pseudoislets (PIs), which consist of aggregates of insulin-secreting pancreatic β-cells. Necrosis arises because of a shortage of nutrient and oxygen diffusion to the core of the PIs during culture, especially when PIs exceed >200 µm. This study aimed to generate ‘vents’ by incorporatin...

A feature of Type 1 diabetes mellitus (T1DM) is the cytokine-induced apoptosis of insulin-secretingBeta cells (β-cells). The cytokines are secreted from macrophages after infiltration into the pancreatic islets of Langerhans. Daily insulin supplementation is the only widely available treatment option for this disease, but this can lead to serious c...

Unfortunately, due to a tagging error, Dr Fiona N. Manderson Koivula’s name is shown incorrectly as Koivula FN on PubMed. Her name appears correctly in the html and pdf versions of the paper.

Introduction Coronary artery disease (CAD) is the leading cause of death worldwide caused by atherosclerosis, now believed to be a complex inflammatory process. Mounting data indicates that the Nucleotide-binding domain, leucine-rich containing family, pyrin domain-containing-3 (NRLP3) inflammasome is critical in the pathogenesis and/or regulation...

Introduction: Management of co- and multi-morbidity continues to represent a major clinical challenge. There remains a lack of understanding of how multiple pathologies or conditions co-evolve or interact and importantly how treatments should be combined to effectively improve outcomes. This review highlights the challenges presented to the clinica...

Cystic fibrosis-related diabetes (CFRD) is the most significant extra-pulmonary comorbidity in cystic fibrosis (CF) patients, and accelerates lung decline. In addition to the traditional view that CFRD is a consequence of fibrotic destruction of the pancreas as a whole, emerging evidence may implicate a role for cystic fibrosis transmembrane-conduc...

Significance This study reports that publicly available gene array expression data together with statistically significant connections’ map successfully predicts licensed drugs able to modify genes of interest. We used this method to predict drugs able to induce A20 [TNFα-induced protein 3 (TNFAIP3)], which is reduced in cystic fibrosis (CF) airway...

Retinal endothelial cell dysfunction is believed to play a key role in the etiology and pathogenesis of diabetic retinopathy. Numerous studies have shown that TRPV4 channels are critically involved in maintaining normal endothelial cell function. In the current paper, we demonstrate that TRPV4 is functionally expressed in the endothelium of the ret...

NF-κB driven inflammation is negatively regulated by the zinc finger protein, A20. Gibberellic acid (GA3 ) is a plant-derived diterpenoid with documented anti-inflammatory activity, which is reported to induce A20-like zinc finger proteins in plants. Here, we sought to investigate the anti-inflammatory effect of GA3 in airway epithelial cells and d...

Background: Cystic fibrosis is an autosomal recessive disease characterised by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The mutations alter fluid secretion in the lungs and digestive systems and the vast majority of patients die from pulmonary disease. CF-related diabetes (CFRD) is the most significant co-mo...

The innate immune response to bacterial infection is mediated through Toll-Like-Receptors, which trigger tightly regulated signaling cascades through transcription factors including Nuclear Factor-kappa B (NF-κB). LPS activation of TLR4 triggers internalisation of the receptor-ligand complex which is directed towards lysosomal degradation or endocy...

Exogenous insulin administration and oral anti-diabetic drugs are the primary means of treating diabetes. However, tight glycaemic control, with its inherent risk of hypoglycaemia, is required to prevent the microvascular and macrovascular complications of the disease. While islet or pancreas transplantations offer a longer-term cure, their widespr...

Background: A20 and TAX1BP1 interact to negatively regulate NF-κB-driven inflammation. A20 expression is altered in F508del/F508del patients. Here we explore the effect of CFTR and CFTR genotype on A20 and TAX1BP1 expression. The relationship with lung function is also assessed. Methods: Primary nasal epithelial cells (NECs) from CF patients (F5...

A20 is a lipopolysaccharide (LPS)-inducible, cytoplasmic zinc finger protein, which inhibits Toll-like receptor-activated nuclear factor (NF)-κB signalling by deubiquitinating tumour necrosis factor receptor-associated factor (TRAF)-6. The action of A20 is facilitated by complex formation with ring finger protein (RNF)-11, Itch and TAX-1 binding pr...

Formation of pseudoislets from rodent cell lines has provided a particularly useful model to study homotypic islet cell interactions and insulin secretion. This study aimed to extend this research to generate and characterize, for the first time, functional human pseudoislets comprising the recently described electrofusion-derived insulin-secreting...

Persistent activation of NF-κB is central to the pathogenesis of many inflammatory lung disorders, including cystic fibrosis, asthma, and chronic obstructive pulmonary disease. A20 is an endogenous negative regulator of NF-κB signaling, which has been widely described in autoimmune and inflammatory disorders, including diabetes and Crohn's disease,...

Close cellular proximity and correct anatomical arrangement within islets are essential for normal patterns of insulin secretion. Thus, segregation of islets into single cells is associated with a dramatic decline in stimulus secretion-coupling and glucose-induced insulin release. Generation of pseudoislets from clonal islet cell lines provides a u...

The incidence of diabetes and the associated debilitating complications are increasing at an alarming rate worldwide. Current therapies for type 1 diabetes focus primarily on administration of exogenous insulin to help restore glucose homeostasis. However, such treatment rarely prevents the long-term complications of this serious metabolic disorder...

Pseudoislet studies have concentrated on single beta-cell lines or a combination of insulin and glucagon-secreting cells, overlooking the potential role of somatostatin in insulin release. This study sought to evaluate a heterotypic pseudoislet model containing insulin- (MIN6), glucagon- (αTC1.9) and somatostatin (TGP52)-secreting cells of mouse or...

Somatostatin, released from pancreatic delta cells, is a potent paracrine inhibitor of insulin and glucagon secretion. Islet cellular interactions and glucose homeostasis are essential to maintain normal patterns of insulin secretion. However, the importance of cell-to-cell communication and cellular environment in the regulation of somatostatin re...

Laboratory-based research aimed at understanding processes regulating insulin secretion and mechanisms underlying β-cell dysfunction and loss in diabetes often makes use of rodents, as these processes are in many respects similar between rats/mice and humans. Indeed, a rough calculation suggests that islets have been isolated from as many as 150,00...

Cellular communication is required for normal patterns of insulin secretion from β cells. Experiments using isolated islets of Langerhans are hampered by lack of supply and the consuming isolation process. Pseudoislets comprising clonal cells have emerged as an alternative to study islet-cell interactions and insulin secretion. The current study co...