Garret A. FitzGerald, MD, FRS
Our laboratory has two areas of interest—prostanoid biology and the role of peripheral molecular clocks in cardiovascular biology, metabolism and aging. Perhaps the distinguishing feature of our groups is that we pursue interdisciplinary translational science with a focus on therapeutics. Thus, we work in different model systems – mammalian cells, worms, fish and mice – but also in humans. Ideally we develop quantitative approaches that can be projected from our experiments in the model systems to guide elucidation of drug action in humans. To this end, we have long utilized mass spectrometry, initially to target the arachidonate derived lipidome, but more latterly also the proteome.
|1974||MB, BCh||University College, Dublin|
|1979||MSc (Statistics)||School of Hygiene, University of London|
|1980||MD (Pharmacology)||University College, Dublin|
Currently, we are interested in several aspects of prostanoid research. We utilize a remarkably broad array of mutant mice to elucidate the biology of the two COX enzymes and the prostanoid receptors. We are particularly interested in the comparative efficacy and safety of pharmacological inhibition of COXs versus the microsomal PGE synthase– 1. We are interested in the potentially countervailing actions of prostanoids on stem cell differentiation and in elucidating the broader cardiovascular biology of prostaglandins D2 and F2α . Finally, besides inhibitors of mPGES–1 we are interested in the translational therapeutics of various receptor antagonists, aspirin and fish oils.
In the area of clock biology, we are probing the role of the clock in aging in mice and worms and using cell specific deletions of core clock components to look at how communication paradigms between discrete peripheral clocks influence cardiovascular biology and metabolism. Finally, we are taking systems approaches to investigate how perturbation of peripheral clocks result in central clock dependent phenotypes.
Finally, we are involved in the interdisciplinary PENTACON consortium designed to integrate basic and clinical research in 5 systems – yeast, mammalian cells, fish, mice and humans ( both in detail and at scale) – with the objective of predicting NSAID efficacy and cardiovascular hazard in patients.
Selected Key Publications