Pharmacology of Lipid Mediators in Inflammation and Resolution
|Head:||Angelo Sala (Associate Professor)|
Christian Pinna (Assistant Professor)
The research group focusses on defining the role of lipid mediators in pulmonary and cardiovascular inflammatory disease. Biosynthetic pathways, biological activities, identification of metabolites and in vivo formation are all aspects that are studied by the lab. Arachidonic, eicosapentaenoic and docosahexaenoic acid metabolites are the families of lipid mediators specifically targeted, with special attention also paid to the role played by the plasmatic concentrations of fatty acid precursors with respect to the formation of biologically active metabolites
1. Mechanisms of biosynthesis and biological activities of lipid mediators arising from polyunsaturated fatty acids.
Research activities aim at defining the mechanisms of biosynthesis of lipid mediators starting from n-3 and n-6 polyunsaturated fatty acids, using different cell types alone or in cocoltures, in consideration of the transcellular mechanisms often involved in the biosynthesis of these molecules. Research activity often is completed with the in vivo determination of lipid mediaotrs using biological samples obtained in collaboration with different clinical groups.
2. identification of biomarkers providing informations about the in vivo formation of lipid mediators.
Research activities aim at the identification of metabolites generated in vivo from the biologically active lipid mediators, with the goal of defining urinary or plasmatic biomarkers of lipid mediaotrs formation in vivo. These biomarkers may prove useful in the development of pharmacological interventions modulating the formation of bioactive lipid mediators.
3. Plasmatic fatty acid profiles in inflammatory disease.
Research activities aim at the characterization of fatty acid profiles in plasma, blood cells or whole blood in pathologies with a significant contribution from the inflammatory response, including cardiovascular (i.e. atherosclerosis), immunological (i.e. rheumatoid arthritis), pulmonary (i.e.cystic fibrosis, COPD)…. Plasmatic fatty acid profile is also used to assess compliance in clinical studies involving supplementation with polyunsaturated fatty acids or other dietary manipulations.
4. Development and characterization of a novel class of anti-inflammatory drugs.
Research activities carried out in collaboration with other national and international groups aim at the development of a new class of non-steroidal anti-inflammatory molecules with improved gastrointestinal and cardiovascular tolerability. These new molecules may be useful in several chronic inflammatory disease, including neurodegenerative disease and specific forms of cancer.
5. Optimization of an animal model of pulmonary fibrosis and characterization of lipid mediators involved.
Research activities carried out in collaboration with Chiesi Farmaceutici, aim at the optimization of the bleomycin model of pulmonary fibrosis in the mouse, defining the potential role of lipid mediators and determining the genomic profile of alveolar lavage cells, with the potential of finding new pharmacological targets to modulate the pulmonary inflammatory response in this model.
6. Characterization of the anti-inflammatory and antioxidant activities of natural products.
Research activities aim at the identification of natural compounds (anthocianins, flavonoids and isoflavones) exerting cytoprotective activities using cells involved in innate immunity or human vessels, with special attention to their anti-inflammatory and antioxidant activities and their effect on the formation of lipid mediators and nitric oxide (NO).
Prof. Sala is a National Research Council Research Associate at I.R.I.B. Experimental Models for Translational Medicine Unit in Palermo.
Prof. Sala is also member of the international network AIR (The Atlas for Inflammation Resolution, https://air.bio.informatik.uni-rostock.de) proposing an international, open platform where clinicians, researchers, students and drug companies interested in the acute and chronic inflammatory response may get in touch and positively interact. The platform goal is supporting clinicians in their choices of patient stratification aimed at providing personalized medicine therapeutic approaches, researchers in defining novel experimental designs and drug companies in the identification of new pharmacological targets.
- Prof. Thierry Durand, and Dr. Laurence Balas, Institut des Biomolécules Max Mousseron (IBMM), UMR 5247, CNRS Université de Montpellier, ENSCM, Montpellier, France.
- Prof. Chiara Bolego, Dipartimento di Farmacologia, UNIPD, Padova
- Prof. Pierachille Santus, Ospedale Luigi Sacco – Polo Universitario and UNIMI, Milano
- Prof. Carlo Agostoni, and prof. Francesco Blasi, IRCSS Fondazione “Ca Granda” Policlinico and UNIMI, Milano
- Dr. Fabio Stellari, dr. Gino Villetti, and dr. Daniela Miglietta, Chiesi Farmaceutici S.p.A. Parma
- Dr. Mirella Profita, IRIB-CNR, Palermo
- Prof. Charles N. Serhan, Director, Center for Experimental Therapeutics and Reperfusion Injury, Brigham and Women’s Hospital, Harvard Medical School, Boston, USA.
- Prof. Gianvincenzo Zuccotti and prof. Elvira Verduci, Dipartimento di Pediatria, Ospedale dei Bambini V. Buzzi and UNIMI, Milano
- Prof. Massimo Bertinaria, Dipartimento di Scienze e tecnologie del Farmaco, UNITO, Torino
- Prof. Dieter Steinhilber and Prof. Eugen Proschak, Institute of Pharmaceutical Chemistry, Johann Wolfgang Goethe University, Frankfurt am Main, Germany.
- Prof. Bruce Hammock, University of California, Davis, USA
- Prof. Gianenrico Rovati, DiSFarm, UNIMI, Milano
- Prof. Paola Patrignani, Dipartimento di Neuroscienze, Imaging e Scienze Cliniche, UNICH, Chieti