Diabetes & Vascular Biology
Understanding and exploiting mechanisms of metabolic and vascular function, pathogenic mechanisms in diabetes and inflammatory disease, as well as new therapeutic approaches that modulate metabolism, inflammation and signalling in vascular disease.
- Influence of nutrition and metabolic phenotypes on vascular function
- Pathogenic mechanisms in diabetes and inflammatory disease
- Vascular remodelling in atherosclerosis, inflammation and hypoxia
- New therapeutic approaches based on the modulation of metabolism, inflammation and signalling in vascular disease.
- Molecular mechanisms underlying diabetic nephropathy including new therapeutic molecules.
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What is the vasculature?
The vasculature encompasses the components of the vessel wall including endothelial and smooth muscle cells, as well as the cellular (e.g erythrocytes, platelets and various types of leucocytes) and soluble components of the blood itself. The vasculature is highly dynamic in many aspects. The vessel wall and blood are exposed to extremes of pressure differences and shear forces and, accordingly, the vasculature has a pronounced capacity for remodelling and renewal.
What is vascular disease?
Vascular disease is a complex process with multiple genetic and environmental factors affecting signaling, metabolism, adhesion, clot formation, growth, immune responses and many other cellular and molecular functions. Myocardial infarction and stroke, for example, arise from increased thrombosis that occurs in damaged arteries typically associated with atherosclerosis.
Vascular disease in Ireland
Vascular disease is a major cause of death in Ireland. In 2010, the Institute of Public Health in Ireland published a study entitled ‘Making Chronic Conditions Count’ showing that chronic conditions such as hypertension, coronary heart disease, stroke and diabetes are expected to increase dramatically over the coming years. The study forecasts a 50% increase in the number of people living with coronary heart disease and a 48% increase in strokes in the Republic of Ireland by 2020. Our current understanding of the origins and mechanisms of vascular disease is limited, as are current treatment options.
Listed below are Conway Fellows involved in vascular biology research
- Assoc. Professor John Baugh
- Professor Orina Belton
- Professor Breandan Kennedy
- Professor B. Therese Kinsella
- Professor Patricia Maguire
- Professor Paul McLoughlin
- Assoc. Professor Tara McMorrow
- Professor Walter McNicholas
- Professor Denis Shields
- Assoc. Professor Albert Smolenski
- Professor Cormac Taylor
Meet our Featured Conway Fellows
Professor B. Therese Kinsella
Our group is mainly focussed on delienation of the mechanisms of signalling and function by the cyclooxygenase-derived prostanoids, prostacyclin and thromboxane, in the regulation of vascular haemostasis. Moreover, we are investigating their roles in contributing to normal and disease processes throughout the vasculature as well as studying their roles in the renal and pulmonary systems and in regulating neoplastic growth. We are using multidisciplinary approaches including elucidation of the mechanisms of signalling by prostacyclin and thromboxane by their cognate receptors, referred to as the IP and TP, respectively; consideration of the structure:function properties of those receptors; use of proteomic approaches to identify novel interacting proteins and/or signalling pathways-regulated by the IP and TP receptors; determination of the transcription factors regulating the expression of the IP and TP genes and design & development of novel antagonists that target the TPα and TPβ isoforms of the human TP (thromboxane receptor). Read more>>
Professor Breandan Kennedy
Currently, we are focusing on the discovery and development of small molecule drugs that inhibit angiogenesis/neovascularisation. Using random and targeted chemical screens in transgenic zebrafish larvae we identify “drug hits” that inhibit developmental angiogenesis. Validated hits are then forwarded to in vitro assays of angiogenesis in human endothelial cells, and to mouse models of pathological ocular neovascularisation and xenograft cancer models. Utlimatley, the goal is to identify novel therapeutics for forms of human blindness and cancer. Read more>>
Assoc. Professor Tara McMorrow
Our group focuses on the study of renal disease, which includes renal vascular disease, with emphasis on mechanisms of initiation and progression. Renal disease is a growing problem worldwide with a 10% annual increase in patients developing chronic kidney disease (CKD). We are currently analysing the mechanisms of renal disease progression, including transcriptomic and proteomic profiles of in vitro and in vivo models of kidney disease with the aim of identifying novel early biomarkers and potential therapeutic targets and strategies. We also focus on ‘Innovative Toxicity Testing for the 21st Century’ with an emphasis in renal toxicogenomics for carcinogens and other chemicals. We collaborate with numerous experimental and clinical collaborators in Ireland and Europe. Read more>> Personal Profile|Laboratory Webpage
Assoc. Professor Albert Smolenski
Our group focuses on the regulation and function of blood platelets. These cells mediate the final thrombotic events in myocardial infarction and stroke and they are likely to be involved in the development of atherosclerosis. We want to understand basic platelet functions to identify new targets for improved anti-thrombotic therapy. Read more>>
Professor Denis Shields
We focus on bioinformatics, with applications in two areas of vascular biology: The first objective is to find short bioactive peptide subsequences of platelet proteins that alter platelet function, giving us insights into cellular signalling and that potentially may provide the templates for therapeutic modulators of thrombosis (involved in heart attacks and stroke). The second is genetics of cardiovascular disease, applied to the ASCOT study, where we seek to understand the role of genetic variation in cardiovascular disease predisposition and outcomes. We work closely with experimental and clinical collaborators at RCSI and UCD. Read more>> Personal profile | Laboratory webpage