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Laboratory of Molecular Pharmacology and Lipid Mediators  

lab Proff. Rovati/Sala

 

Research topics

In vitro/ex vivo characterization of new molecules with antithrombotic and anti inflammatory activity; evaluation and quali-quantitative determination of lipid mediators, in particular, arachidonic and docosahexaenoic acid metabolites, produced by different cell types both ex vivo and cultured, and in organs and tissues, evaluating also the lipid composition, i.e. the fatty acid composition of phospholipids.

Studies, at molecular level, of the eicosanoid receptors, ligand-receptor interactions and new agonists and antagonists identification. The laboratory has been dealing for years with the molecular pharmacology of G protein-coupled receptors and, in particular, of leukotriene and thromboxane receptors and their classification; new potential receptor characterization, activation and dimer formation, and their functioning and transduction pathways. In addition, the laboratory is working on the characterization of drugs, previously utilized as anti-asthmatics, that might demonstrate protective cardiovascular effects (drug repurposing).

Study of the potential protective activity of metabolites derived from plants (flavonoids, isoflavones, antocyans) on vascular endothelium and of their vasorelaxing activity on human umbilical vein.

 

Techniques

Human blood cells isolation and purification, induction of an inflammatory response, functionality evaluation and pharmacological modulation, platelet aggregation test.

Models of isolated, purified circulating cell interactions, in complex organ systems/cultured cells.

Quali/quantitative evaluation of lipid mediators and derivatives by chromatographic techniques (GC, HPLC, triple-quadrupole and ion trap mass spectrometers).

Cultured cells, drug-receptor interaction (binding), second messenger analysis (cAMP, Ca++, inositol phosphates, etc), molecular biology techniques (transfection with recombinant DNA, site-specific mutations, western and northern blot). 

 

Collaborators

Prof. Carlo Agostoni, IRCSS Fondazione ‘Ca Granda, Policlinico Milano
Prof. Stefano Aliberti, IRCSS Fondazione ‘Ca Granda, Policlinico Milano
Prof.ssa Chiara Bolego, professore associato Università di Padova
Dott.sse Bice Chini e Marta Busnelli, Istituto di Bioscienze-CNR Milano
Prof.ssa Paola Patrignani, UNICH, Chieti
Prof. Richard R. Neubig, Chair of Department of Pharmacology, Michigan State University, Michigan, USA
Prof. Thierry Durand, Institut des Biomolécules Max Mousseron (IBMM), UMR 5247, CNRS Université de Montpellier, ENSCM, F-34093 Montpellier, France.
Dott.ssa Mirella Profita, IBIM-CNR Palermo
Prof. Eugen Proschak Institute of Pharmaceutical Chemistry, Johann Wolfgang Goethe University, Max-von-Laue-Strasse 9, D-60438 Frankfurt am Main, Germany.
Prof. Dieter Steinhilber Institute of Pharmaceutical Chemistry, Johann Wolfgang Goethe University, Max-von-Laue-Strasse 9, D-60438 Frankfurt am Main, Germany.
Dott. Fabio Stellari, Gino Villetti, Chiesi Farmaceutici S.p.A. Parma

 

Selected publications

1. Sala A, Proschak E, Steinhilber D, Rovati GE. Two-Pronged Approach to Anti-Inflammatory Therapy Through the Modulation of the Arachidonic Acid Cascade. Biochemical Pharmacology. 2018; 158:161-73. doi: 10.1016/j.bcp.2018.10.007.

2. Schierle S, Flauaus C, Heitel P, Willems S, Schmidt J, Kaiser A, Weizel L, Goebel T, Kahnt AS, Geisslinger G, Steinhilber D, Wurglics M, Rovati GE, Schmidtko A, Proschak E, Merk D. Boosting Anti-Inflammatory Potency of Zafirlukast by Designed Polypharmacology. J Med Chem. 2018 Jul 12;61(13):5758-5764. doi: 10.1021/acs.jmedchem.8b00458. 

3. Carnevali S, Buccellati C, Bolego C, Bertinaria M, Rovati GE, Sala A. Nonsteroidal Anti-Inflammatory Drugs: Exploiting Bivalent COXIB/TP Antagonists for the Control of Cardiovascular Risk. Current Medicinal Chemistry. 2017 Jun; 24(30):3218-30. doi: 10.2174/0929867324666170602083428

4. Capra V, Mauri M, Guzzi F, Busnelli M, Accomazzo MR, Gaussem P, et al. Impaired thromboxane receptor dimerization reduces signaling efficiency: A potential mechanism for reduced platelet function in vivo. Biochem Pharmacol. 2017; 124:43–56.

5. Toniolo A, Buccellati C, Pinna C, Gaion RM, Sala A, Bolego C. Cyclooxygenase-1 and prostacyclin production by endothelial cells in the presence of mild oxidative stress. PLoS One. (2013) 8(2), e56683 

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