CERIC
JESPER Z. HAEGGSTRÖM

Jesper

Department of Medical Biochemistry and Biophysics, Division of Physiological Chemisty 2, Karolinksa Institutet

Laboratory Homepage

jesper.haeggstrom@ki.se

Tel: 08-524 876 12

Group Members

Faculty:
Anders Wetterholm, PhD
Craig Wheelock, PhD

Post-doctoral fellows:
Fabio Dalexandri, PhD,
Agnes Rinaldo-Matthis, PhD
Susanna Lundström, PhD
Antonio Di Gennaro, PhD
Ulrike Haas, PhD
Alicia Hidalgo, PhD

PhD students:
Min Wan

Technical and administrative staff:
Eva Ohlson, technician
Anneli Svarén, adminstrator

 

 

 

Arachidonic acid is the precursor of a broad spectrum of bioactive lipids in plants and animals. In mammals, the most well known classes are the prostaglandins, thromboxanes, leukotrienes and lipoxins which all have powerful and diverse biological activities related to a multitude of physiological as well as pathological conditions.

Our research is focused on a family of lipid mediators called the leukotrienes (LT) involved in a number of inflammatory and allergic diseases, in particular asthma, rheumatoid arthritis, and arteriosclerosis. We investigate the biosynthetic and regulatory mechanisms involved in leukotriene formation at a cellular, enzyme, and genetic level with particular emphasis on 5-lipoxygenase (5-LO), LTA4 hydrolase (LTA4H) and LTC4 synthase (LTC4S). These three enzymes catalyze the key steps in the biosynthesis of the proinflammatory compounds LTB4 and LTC4.

Based on research on metabolites and proteins in the arachidonic cascade, a number of new drugs against inflammation, allergy, asthma and glaucoma have been developed and new pharmacological principles continuously evolve from this research area.


Research interactions with CERIC

Studies on the role of eicosanoids in atherosclerosis and CVD

Elucidation of lipid and peptide mediator synergies in the innate immune response

Impact of CMV infection on cellular eicosanoid synthesis and actions

Effects of anti-inflammatory, anti-rheumatic drugs on the eicosanoid cascade


Selected Publications
Hammarberg T, Hamberg M, Wetterholm A, Hansson H, Samuelsson B, Haeggström JZ. Mutation of a critical arginine in microsomal PGE synthase-1 shifts the isomerase activity to a reductase activity that converts prostaglandin H2 into prostaglandin F2alpha. J Biol Chem. 2008 Nov 3. [Epub ahead of print]

Tholander F, Muroya A, Roques BP, Fournié-Zaluski MC, Thunnissen MM, Haeggström JZ. Structure-based dissection of the active site chemistry of leukotriene A4 hydrolase: implications for M1 aminopeptidases and inhibitor design. Chem Biol. 2008; 15(9):920-929.

Qiu H, Strååt K, Rahbar A, Wan M, Söderberg-Nauclér C, Haeggström JZ. Human CMV infection induces 5-lipoxygenase expression and leukotriene B4 production in vascular smooth muscle cells. J Exp Med. 2008; 205(1):19-24.

Martinez Molina D, Wetterholm A, Kohl A, McCarthy AA, Niegowski D, Ohlson E, Hammarberg T, Eshaghi S, Haeggström JZ, Nordlund P. Structural basis for synthesis of inflammatory mediators by human leukotriene C4 synthase. Nature. 2007; 448(7153):613-616.

Qiu H, Gabrielsen A, Agardh HE, Wan M, Wetterholm A, Wong CH, Hedin U, Swedenborg J, Hansson GK, Samuelsson B, Paulsson-Berne G, Haeggström JZ. Expression of 5-lipoxygenase and leukotriene A4 hydrolase in human atherosclerotic lesions correlates with symptoms of plaque instability. Proc Natl Acad Sci U S A. 2006; 103(21):8161-8166.

 

Home