Research Division of Physiological Chemistry II
The division employs a range of techniques in cellular, molecular, and structural biology together with animal models and LC-MS based lipid profiling with the goal to understand the role of eicosanoids and other lipid mediators in host defense and human diseases.
Our division is focused on bioactive lipids, in particular the eicosanoids, a family of oxygenated metabolites of arachidonic acid encompassing prostaglandins, thromboxanes, leukotrienes, and lipoxins. These paracrine hormones play both physiological and pathogenic roles in man, in particular as signaling molecules in innate immune responses and inflammation within the respiratory and cardiovascular systems. We study all aspects of these mediators including chemical and structural identification of metabolites, cellular activation and regulation of eicosanoid biosynthesis, as well as biochemical and structural characterization of the enzymes and regulatory proteins of the biosynthetic pathways. In recent years, we have put special efforts into translation of our basic knowledge into clinical and applied projects, using collections of patient samples and animal models, in collaboration with clinical teams.
The eicosanoid cascade has generated a number of successful drugs such as NSAIDs, coxibs, latanoprost, and lukasts for treatment of pain, fever, arthritis, glaucoma, and asthma. As a consequence, part of our work is carried out in alliance with pharmaceutical industry.
Jesper Z. Haeggström Group
The eicosanoids, a family of lipid mediators in health and disease
Structures of Leukotriene Biosynthetic Enzymes and Development of New Therapeutics.
Haeggström JZ, Newcomer ME
Annu Rev Pharmacol Toxicol 2023 Jan;63():407-428
Dosage differences in 12-OXOPHYTODIENOATE REDUCTASE genes modulate wheat root growth.
Gabay G, Wang H, Zhang J, Moriconi JI, Burguener GF, Gualano LD, Howell T, Lukaszewski A, Staskawicz B, Cho MJ, Tanaka J, Fahima T, Ke H, Dehesh K, Zhang GL, Gou JY, Hamberg M, Santa-María GE, Dubcovsky J
Nat Commun 2023 Feb;14(1):539
Crystal structures of human MGST2 reveal synchronized conformational changes regulating catalysis.
Thulasingam M, Orellana L, Nji E, Ahmad S, Rinaldo-Matthis A, Haeggström JZ
Nat Commun 2021 Mar;12(1):1728
Human leukocytes selectively convert 4S,5S-epoxy-resolvin to resolvin D3, resolvin D4, and a cys-resolvin isomer.
Shay AE, Nshimiyimana R, Samuelsson B, Petasis NA, Haeggström JZ, Serhan CN
Proc Natl Acad Sci U S A 2021 Dec;118(51):
Dicer up-regulation by inhibition of specific proteolysis in differentiating monocytic cells.
Basavarajappa D, Uebbing S, Kreiss M, Lukic A, Suess B, Steinhilber D, Samuelsson B, Rådmark O
Proc Natl Acad Sci U S A 2020 Apr;117(15):8573-8583
Integral Membrane Enzymes in Eicosanoid Metabolism: Structures, Mechanisms and Inhibitor Design.
Thulasingam M, Haeggström JZ
J Mol Biol 2020 Aug;432(18):4999-5022
Activation of metabolite receptor GPR91 promotes platelet aggregation and transcellular biosynthesis of leukotriene C4.
Tang X, Fuchs D, Tan S, Trauelsen M, Schwartz TW, Wheelock CE, Li N, Haeggström JZ
J Thromb Haemost 2020 Apr;18(4):976-984
Cysteinyl leukotriene receptor 1 antagonism prevents experimental abdominal aortic aneurysm.
Di Gennaro A, Araújo AC, Busch A, Jin H, Wågsäter D, Vorkapic E, Caidahl K, Eriksson P, Samuelsson B, Maegdefessel L, Haeggström JZ
Proc Natl Acad Sci U S A 2018 Feb;115(8):1907-1912
Leukotriene biosynthetic enzymes as therapeutic targets.
J Clin Invest 2018 Jul;128(7):2680-2690
An OPR3-independent pathway uses 4,5-didehydrojasmonate for jasmonate synthesis.
Chini A, Monte I, Zamarreño AM, Hamberg M, Lassueur S, Reymond P, Weiss S, Stintzi A, Schaller A, Porzel A, García-Mina JM, Solano R
Nat Chem Biol 2018 Feb;14(2):171-178
Division of Physiological Chemistry II
Biomedicum, 9A, floor 9
171 65 Solna