The Irish Association of Pharmacologists:
Executive Committee 2016-2018
He served as Clinical Vice-President of the British Pharmacological Society from 2007 to 2010. He is currently the managing editor of the European journal of Clinical Pharmacology. In 2009, he was appointed Associate Professor in Geriatric Medicine at the Royal College of Surgeons in Ireland / Beaumont Hospital, where he has helped develop the Acute Stroke Service and undergraduate teaching curriculum in Geriatric Medicine.
Professor Williams is currently the National Speciality Director of training for Clinical Pharmacology and Therapeutics. His research interests include Stroke Medicine, Hypertension, Patient Safety, Prescribing and Medication Errors.
Professor Williams’s research interests include Pharmacoepidemiology and Patient safety, Vascular medicine and Drug Metabolism. His PhD thesis was based on examining prescribing patterns and measures of prescribing quality within the General Medical Services (GMS) scheme in Ireland. Studies in pharmacovigilance, drug utilisation and prescribing quality were performed which led to a number of publications and demonstrated the usefulness of such a database in examining real world prescribing patterns. Recent work has focussed on inequalities in prescribing in patients with cardiovascular disease and stroke.
Professor Williams’s Clinical Research is focussed on vascular and stroke medicine with a particular interest in arterial compliance, hypertension and platelet function. Following validation of the technique of pulse wave analysis (PWA) in assessing arterial compliance he embarked on a number of studies in this field. Professor Williams has previously investigated aspirin resistance (those with a true biochemical defect which makes them resistant to the thromboxane pathway-inhibiting effects of aspirin) in patients with ischaemic stroke who are already receiving aspirin by examining platelet aggregation, platelet activation status and thromboxane generation. He has previously obtained funding from Heart Research UK to examine the phenomenon of a rebound in platelet activity following the cessation of clopidogrel therapy.
Ten years ago, Dr Waeber switched topics, largely abandoning research on 5-HT to focus on the role of sphingosine-1-phosphate (S1P) receptors in blood vessels and brain. These blood vessel studies are significant for the treatment of cerebrovascular disorders (e.g. stroke, vasospasm), and conditions such as diabetes, atherosclerosis, pulmonary hypertension or cancer. Dr. Waeber’s team has also shown that S1P receptors have a widespread distribution both in adult and developing brain. They have characterized the CNS distribution of the S1P synthesizing enzyme, sphingosine kinase (SK), showing that it is up-regulated in neurons following ischemia. Finally, they have shown that stimulating S1P receptors with a pharmacological agent (FTY720/fingolimod) or endogenously-produced S1P (preconditioning) protects the brain from ischemia-induced damage. Finally, Dr. Waeber’s team has shown that administering fingolimod as late as 24 hours after reperfusion in a mouse model promotes long-term stroke recovery. His team has recently published that fingolimod reduces the neurological deficit and infarct volume after in situ thrombo-embolic occlusion of the middle cerebral artery, a model likely to better mimic the features of stroke in humans: combination of fingolimod and tPA improved the neurological outcome of the thrombolytic therapy and reduces the risk of hemorrhagic transformation associated to delayed administration to tPA.
Dr. Barry’s area(s) of interest are how tumour signalling events drive oncogenic progression and how strategic events can be exploited to develop more effective treatment options. Her laboratory focuses on the study of different families of serine/threonine kinases that play key roles in signalling mechanisms following activation of seven-transmembrane and receptor tyrosine-kinases. In particular her group explores the role of Paks, p38 MAPKs, and PKCs which exert a variety of cellular effects including changes in proliferation, malignant transformation, cell death and differentiation. Her research has exploited the activation of p38 MAPK as well as PKC as a pro-apoptotic and anti-proliferative agent in oesophageal cancer. Re-introduction of p38 MAPK into different cancers which lack this isoform including oesophageal, renal, prostate, lung and liver has had profound effects on cancer cell proliferation and apoptosis. An important aspect of her research is to also elucidate the signalling pathways underlying the apoptotic effect of these kinases using both pharmacological and molecular experimental approaches. The identification of different kinase isoforms involved in cell proliferation and cell death in different types of cancer may have important therapeutic implications for the treatment of the disease.
In addition Dr. Barry is also exploring how epigenetic changes to the genome contribute to the progression of cancer. In particular the search for biomarkers like hyper- or hypo-methylated genes in oesophageal cancer in the context of early detection or diagnostic markers, or predicting response to treatment is an area of active research.
In 2007, he was appointed to the Chair of Biomedical Sciences and held the full professorship of Cardiovascular Physiology at the Hull, York Medical School, University of Hull, UK. In August 2009, he was recruited by the University of Giessen, Germany to establish the Department of Experimental Cardiology and held the commission for the Excellence Cluster Cardio-Pulmonary System (ECCPS) for the Department until July 2011. In 2009 and 2010 he was appointed to two Visiting Professorships at the University of Leipzig, Germany and at the University of Ipatinga, Brazil, respectively.
The international orientation of Prof. Thomas Walther’s research has increasingly gained in importance over the past years, especially in the fields of programs that combine basic and translational research in order to improve the prediction and treatment of cardiovascular diseases. He is consequently following the strategy of molecular investigation, followed by evaluation in animal models, and finally establishing proof of concept in humans aiming to find new therapeutic strategies.
Using these complex approaches, he is investigating the role of three different peptide systems (renin-angiotensin system, kallikrein-kinin system, natriuretic peptide system) in the aetiology of different diseases, mainly focused on cardiovascular pathophysiology in end-organs such as the brain or heart. Since identifying intense interactions of these systems, he is interested in finding out how an imbalance of cross-talk can influence the development of heart failure and vascular diseases. These investigations are especially focused on altered gene regulation, modified receptor/receptor interaction, and receptor mediated intracellular signalling.
Professor Walther’s main aims are to continue improving the understanding of the roles of these important signalling systems in cardiovascular disease and to identify pharmacological targets for new drugs. The ultimate aim is to improve patient outcome from cardiovascular conditions. Over the last ten years this research has resulted in over 110 papers published in peer reviewed scientific journals.