Christian Waeber joined University College Cork (UCC) in 2013; he is Professor of Pharmacology, a joint appointment between the School of Pharmacy and the Department of Pharmacology. He is currently Head of the Department of Pharmacology and Therapeutics. Early in his career, Christian worked as a Ph.D. student at Novartis Basel, where he characterized the pharmacological profile, signalling pathways and brain distribution of 5-HT1D receptors. Christian then joined as a post-doctoral fellow the laboratory of Joel Bockaert, at the “Centre CNRS-INSERM de Pharmacologie-Endocrinologie” in Montpellier. In 1993, he joined Harvard Medical School to characterize the pharmacological profile of 5-HT1-like receptors inhibiting neurogenic inflammation, a research carried out in collaboration with Michael Moskowitz. Their work led to the suggestion that specific 5-HT1F receptor agonists would be effective acute antimigraine agents devoid of cardiovascular side-effects. The recent approval of Lasmiditan proved this notion to be correct. Over the last 20 years, Christian has moved away from 5-HT to focus on the role of sphingosine-1-phosphate (S1P) receptors in various pathophysiological processes. His studies on blood vessels are significant for the treatment of cerebrovascular disorders (e.g. stroke, vasospasm), and conditions such as diabetes, atherosclerosis, pulmonary hypertension or cancer. Christian’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, Christian’s team has shown that administering

My research is centered on the role of sphingosine-1-phosphate (S1P) receptor stimulation in various pathological conditions. My team has shown that S1P receptors have a widespread distribution both in the adult and in the developing brain, in which S1P might play a key role, based on our finding that it induces proliferation and morphological changes of neural progenitor cells. We have also characterized the distribution of the S1P synthesizing enzyme, sphingosine kinase (SPK), in brain, shown that it is up-regulated in neurons following ischemia. Finally, we have shown that stimulating S1P receptors with a pharmacological agent (FTY720/fingolimod) or endogenously-produced S1P protects the brain from ischemia-induced damage. My current studies center on preconditioning and neuroprotection in the context of ischemic stroke and intracerebral haemorrhage, and aim at better understanding the role of the adaptive immune system in stroke outcome. 1. Preconditioning (in which a stimulus below the threshold of damage is applied, leading to tissue resistance to the same, or different stimuli given beyond damage threshold) is an attractive experimental strategy to identify endogenous protective mechanisms that could be therapeutically implemented. The lipid mediator sphingosine 1-phosphate (S1P) plays a role in preconditioning, protecting the heart and kidney against ischemia/reperfusion injury. Sphingosine kinase 2 (SK2) is the major S1P-synthezising enzyme in brain and is up-regulated in neurons in response to ischemia. SK2 is a BH3-only protein, that can interact with the cell death-related protein Bcl-xL, suggesting that this enzyme isoform has S1P-independent actions. Together with colleagues at Soochow University, we have shown that TAT-SPK2 peptide protects against cerebral ischemia/reperfusion neuronal injury both in vivo and in vitro. TAT-SPK2 directly binds to Bcl-2 and disrupts the Becl

Pathophysiology and pharmacology of migraine and stroke. Biochemical pharmacology of G protein-coupled receptors Vascular physiology Central Nervous System Pharmacology and Therapeutics