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Garret A. FitzGerald, MD
Garret A. FitzGerald, MD
University of Pennsylvania
Institute for Translational Medicine and Therapeutics
3400 Civic Center Blvd., Building 421
10-122 Smillow Center for Translational
Philadelphia, PA 19104-6160
The FitzGerald Laboratory has two areas of interest — prostanoid biology and the role of peripheral molecular clocks in cardiovascular biology, metabolism and aging.
The distinguishing feature of the groups within the FitzGerald Lab is the pursuit of interdisciplinary translational science with a focus on therapeutics. As a result, the Lab works in different model systems — mammalian cells, fish and mice — but also in humans. Ideally, these experiments result in the development of quantitative approaches that can be projected in the model systems to guide elucidation of drug action in humans. To this end, the Lab has long utilized mass spectrometry, initially to target the arachidonate-derived lipidome, but more latterly the proteome, as well. Because these approaches generate a great deal of data, the Lab has integrated statisticians and bioinformaticians directly into the group for many years.
More than 120 postdoctoral trainees have passed through the FitzGerald Laboratory in the thirty years of its existence. Roughly half are MDs or MD – PhDs and of the former group roughly half have never been in a laboratory before.
Graduates of the program have moved on to faculty and administrative roles in academia, scientific appointments in pharma and biotech, jobs in funding bodies and the financial sector. The laboratory is heavily biased towards postdocs but there are usually 2 or 3 graduate students in the group as well.
If you want a training experience that blends the rigor of basic science with the relevance to human health of clinical research, this is the place for you.
Currently, the research ongoing at the FitzGerald Lab is concentrated in two primary areas; the cardiovascular biology of eicosanoids and related compounds, and the role of peripheral clocks in cardiovascular biology, metabolism and inflammation.
The FitzGerald Lab is pursuing several aspects of prostanoid research using a remarkably broad array of mutant mice to elucidate the biology of the two COX enzymes and the prostanoid receptors.
The Lab is particularly interested in:
- the comparative efficacy and safety of pharmacological inhibition of COXs versus the microsomal PGE synthase– 1;
- the potentially countervailing actions of prostanoids on stem cell differentiation;
- elucidating the broader cardiovascular biology of prostaglandins D2 and F2α; and
- the translational therapeutics of various receptor antagonists, aspirin and fish oils.
In the area of clock biology, the FitzGerald Lab is probing the role of the clock in aging in mice and worms and using cell specific deletions of core clock components to examine communication paradigms between discrete peripheral clocks influence cardiovascular biology and metabolism. In addition, the Lab is taking systems approaches to investigate how perturbation of peripheral clocks results in central clock dependent phenotypes.
The Lab is also involved in the interdisciplinary PENTACON consortium designed to integrate basic and clinical research in five 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.
- Song WL, Stubbe J, Riciotti E, Alamuddin N, Ibrahim S, Paschos G, Ricciotti E, Crichton I, Prempah M, Lawson JA, Wilensky RL, Puré E, Rasmussen LM, FitzGerald GA. Niacin and biosynthesis of PGD₂ by platelet COX-1 in mice and humans. J Clin Invest. 2012;122:1459-1468.
- Yu Z, Crichton I, Tang SY, Hui Y, Ricciotti E, Levin MD, Lawson JA, Puré E, FitzGerald GA. Disruption of the 5 – lipoxygenase pathway attenuates atherogenesis consequent to COX-2 deletion in mice. Proc Natl Acad Sci. 2012;109:6727-6732.
- Yu Y, Riciotti E, Scalia R, Tang SY, Grant G, Xiong Y, Yu Z, Landesberg G, Crichton I, Wu W, Puré E, Funk CD, FitzGerald GA. Vascular COX-2 modulates blood pressure and thrombosis in mice. Sci Transl Med. 2012;4:132ra54.
- Hui Y, Ricciotti E, Crichton I, Yu Z, Wang D, Stubbe J, Wang M, Puré E, FitzGerald GA. Targeted deletions of cyclooxygenase-2 and atherogenesis in mice. Circulation. 2010;121:2654-2660.