Inflammation and liver disease. PI: Joan Clària Enrich

Presentation

Our group is mainly interested in the study of the molecular mechanisms underlying the inflammatory process commonly observed in chronic liver disease. One of the priorities of our research is to characterize the genetic component that modifies the inflammatory response in these patients. In this regard, our group has identified a number of polymorphisms in genes coding for inflammatory mediators such as cytokines (e.g. interleukin-1 (IL-1) and IL-1 receptor antagonist (IL-1ra)), as well as in genes coding for anti-inflammatory and pro-resolving factors such as chemR23 receptor. In addition to research in patients, our group also conducts basic and translational research in the area of chronic liver disease. On one hand, we discern the mechanistic aspects of the inflammatory response in individual inflammatory cells, especially macrophages. On the other hand, we perform studies in experimental models of liver disease of metabolic origin (i.e. obesity-induced steatohepatitis) aimed at evaluating novel therapeutic approaches that could harness the unremitting inflammatory response.

Joan Clària Enrich
Associate professor
jclaria@clinic.cat

Esther Titos Rodriguez
Assistant professor
esther.titos@ciberehd.org

Cristina López Vicario
Postdoctoral researcher
clopezv@clinic.cat

Sílvia Sanz Sender
Investigadora Postdoctoral

SSANZ1@clinic.cat

Nayra Rico Santana
Senior specialist
nrico@clinic.cat

José Alcaraz-Quiles
Specialist
joalcara@clinic.cat

Mireia Casulleras Olivé
Predoctoral researcher
mcasulleras@clinic.cat

Marta Duran Güell
Predoctoral researcher
madurang@clinic.cat

Roger Flores Costa
Predoctoral researcher
roflores@clinic.cat

Anabel Martínez
Laboratory technician
amartin4@clinic.cat

Albert Salvatella
Laboratory technician
salvatella@clinic.cat

Monica Romo
Investigador Predoctoral
romo@clinic.cat

Ingrid Wei Zhang
Investigadora Postdoctoral
ingrid-wei.zhang@charite.de

  • Liver inflammation associated with obesity

  • Genes and molecular pathways involved in inflammation

  • Genetic factors that modify the inflammatory response

  • Mediators of inflammation of lipid nature

  • MICROB-PREDICT (MICROBiome-based biomarkers to PREDICT decompensation of liver cirrhosis and treatment response)

Horizon2020
2019-2024
15.000.000 €

  • Grup de Recerca Consolidat (2017SGR1449). Grup: Investigació hepática: recerca bàsica i experimental

Beca AGAUR (Generalitat de Catalunya)
2017-2019
31.224 €

  • In vitro, ex vivo and in vivo evaluation of the anti-inflammatory effects of human albumin

European Foundation for the Study of Chronic Liver Failure
2018
210.000 €

  • Anti-inflammatory and anti-fibrogenic effects of a new soluble guanylate cyclase stimulator alone or in combination with obeticholic acid in mice with non-alcoholic esteatohepatitis

Ironwood Pharmaceuticals
2018-2019
64.990 €

  • Assessment of the ability of a new soluble guanylate cyclase stimulator to therapeutically reverse inflammation and overt fibrosis in insulin sensitive tissues

Ironwood Pharmaceuticals
2017-2018
77.000 €

  • Identification of new lipidomic “eicosanomic” signatures in decompensated cirrhotic patients with acute on chronic liver failure

European Foundation for the Study of Chronic Liver Failure
2017-2019
18.000 €

  • Effects of native (reduced) and oxidized albumin forms on human leukocyte function

Grifols Institute
2017-1019
50.000 €

  • Mecanismos moleculares determinantes de la resolución inadecuada de la inflamación en tejido adiposo obeso. Nuevas oportunidades en la prevención de comorbilidades metabólicas.

Ministerio de Economía y Competitividad (SAF 15/63674-R)
2015-2018
210.000 €

For more information for PI publications click in the link:
ORCID: https://orcid.org/0000-0003-4333-7749
ResearcherID:https://www.scopus.com/authid/detail.uri?authorId=36770842900

Trebicka J, Amoros A, Pitarch C, Titos E, Alcaraz-Quiles J, Schierwagen R, Deulofeu C, Fernandez-Gomez J, Piano S, Caraceni P, Oettl K, Sola E, Laleman W, McNaughtan J, Mookerjee RP, Coenraad MJ, Welzel T, Steib C, Garcia R, Gustot T, Rodriguez Gandia MA, Bañares R, Albillos A, Zeuzem S, Vargas V, Saliba F, Nevens F, Alessandria C, de Gottardi A, Zoller H, Ginès P, Sauerbruch T, Gerbes A, Stauber RE, Bernardi M, Angeli P, Pavesi M, Moreau R, Clària J, Jalan R, Arroyo V. Addressing Profiles of Systemic Inflammation Across the Different Clinical Phenotypes of Acutely Decompensated Cirrhosis. Front Immunol. 2019 Mar 19;10:476. doi: 10.3389/ fimmu.2019.00476. eCollection 2019. PMID: 30941129

Fernández J, Clària J, Amorós A, Aguilar F, Castro M, Casulleras M, Acevedo J, Duran-Güell M, Nuñez L, Costa M, Torres M, Horrillo R, Ruiz-Del-Árbol L, Villanueva C, Prado V, Arteaga M, Trebicka J, Angeli P, Merli M, Alessandria C, Aagaard NK, Soriano G, Durand F, Gerbes A, Gustot T, Welzel TM, Salerno F, Bañares R, Vargas V, Albillos A, Silva A, Morales-Ruiz M, Pavesi M, Jalan R, Bernardi M, Moreau R, Páez A, Arroyo V. Effects of Albumin Treatment on Systemic and Portal Hemodynamics and Systemic Inflammation in Patients With Decompensated Cirrhosis. Gastroenterology. 2019 Mar 21. pii: S0016-5085 (19)33576-0. doi: 10.1053/ j.gastro.2019.03.021. [Epub ahead of print]. PMID: 30905652

López-Vicario C, Titos E, Walker ME, Alcaraz-Quiles J, Casulleras M, Durán-Güell M, Flores-Costa R, Pérez-Romero N, Forné M, Dalli J, Clària J. Leukocytes from obese individuals exhibit an impaired SPM signature. FASEB J. 2019 Mar 6:fj201802587R. doi: 10.1096/ fj. 201802587R. [Epub ahead of print]. PMID: 30840838

Alvarez-Silva C, Schierwagen R, Pohlmann A, Magdaleno F, Uschner FE, Ryan P, Vehreschild MJGT, Claria J, Latz E, Lelouvier B, Arumugam M, Trebicka J. Compartmentalization of Immune Response and Microbial Translocation in Decompensated Cirrhosis. Front Immunol. 2019 Feb 8;10:69. doi: 10.3389/ fimmu.2019.00069. eCollection 2019. PMID: 30800122

Carracedo M, Artiach G, Witasp A, Clària J, Carlström M, Laguna-Fernandez A, Stenvinkel P, Bäck M. The G-protein coupled receptor ChemR23 determines smooth muscle cell phenotypic switching to enhance high phosphate-induced vascular calcification. Cardiovasc Res. 2018 Dec 28. doi: 10.1093/cvr/cvy316. [Epub ahead of print] PMID: 30597013

Clària J, Moreau R, Fenaille F, Amorós A, Junot C, Gronbaek H, Coenraad MJ, Pruvost A, Ghettas A, Chu-Van E, López-Vicario C, Oettl K, Caraceni P, Alessandria C, Trebicka J, Pavesi M, Deulofeu C, Albillos A, Gustot T, Welzel TM, Fernández J, Stauber RE, Saliba F, Butin N, Colsch B, Moreno C, Durand F, Nevens F, Bañares R, Benten D, Ginès P, Gerbes A, Jalan R, Angeli P, Bernardi M, Arroyo V; CANONIC Study Investigators of the EASL Clif Consortium, Grifols Chair and the European Foundation for the Study of Chronic Liver Failure (EF Clif). Orchestration of Tryptophan-Kynurenine Pathway, Acute Decompensation, and Acute-on-Chronic Liver Failure in Cirrhosis. Hepatology. 2019 Apr; 69(4): 1686-1701. doi: 10.1002/ hep.30363. Epub 2019 Mar 19. PMID: 30521097

Artiach G, Carracedo M, Clària J, Laguna-Fernandez A, Bäck M. Opposing Effects on Vascular Smooth Muscle Cell Proliferation and Macrophage-induced Inflammation Reveal a Protective Role for the Proresolving Lipid Mediator Receptor ChemR23 in Intimal Hyperplasia. Front Pharmacol. 2018 Nov 20;9: 1327. doi: 10.3389/ fphar.2018. 01327. eCollection 2018. PMID: 30515096

Laleman W, Claria J, Van der Merwe S, Moreau R, Trebicka J. Systemic Inflammation and Acute-on-Chronic Liver Failure: Too Much, Not Enough. Can J Gastroenterol Hepatol. 2018 Aug 1;2018: 1027152. doi: 10.1155/2018 /1027152. eCollection 2018. Review. PMID: 30155448

Alcaraz-Quiles J, Casulleras M, Oettl K, Titos E, Flores-Costa R, Duran-Güell M, López-Vicario C, Pavesi M, Stauber RE, Arroyo V, Clària J. Oxidized Albumin Triggers a Cytokine Storm in Leukocytes Through P38 Mitogen-Activated Protein Kinase: Role in Systemic Inflammation in Decompensated Cirrhosis. Hepatology. 2018 Nov;68(5):1937-1952. doi: 10.1002/hep.30135. Epub 2018 Oct 13. PMID: 30070728

Lopategi A, Flores-Costa R, Rius B, López-Vicario C, Alcaraz-Quiles J, Titos E, Clària J. Frontline Science: Specialized proresolving lipid mediators inhibit the priming and activation of the macrophage NLRP3 inflammasome. J Leukoc Biol. 2019 Jan;105(1): 25-36. doi: 10.1002/ JLB.3HI0517- 206RR. Epub 2018 Mar 30. PMID: 29601102

Flores-Costa R, Alcaraz-Quiles J, Titos E, López-Vicario C, Casulleras M, Duran-Güell M, Rius B, Diaz A, Hall K, Shea C, Sarno R, Currie M, Masferrer JL, Clària J. The soluble guanylate cyclase stimulator IW-1973 prevents inflammation and fibrosis in experimental non-alcoholic steatohepatitis. Br J Pharmacol. 2018 Mar; 175(6): 953-967. doi: 10.1111/ bph.14137. Epub 2018 Jan 31. PMID: 29281143

Arroyo V, Clària J. Acute-on-Chronic Liver Failure, Human Serum Albumin, and Immune Modulation: The Beginning of an Exciting Adventure. Clin Gastroenterol Hepatol. 2018 May; 16(5): 633-636. doi: 10.1016/ j.cgh.2017.12.008. Epub 2017 Dec 12. No abstract available. PMID: 29246698

López-Vicario C, Rius B, Alcaraz-Quiles J, González-Périz A, Martínez-Puchol AI, Casulleras M, Duran-Güell M, Ibarzabal A, Corcelles R, Laguna-Fernández A, Back M, Titos E, Clària J. Association of a variant in the gene encoding for ERV1/ChemR23 with reduced inflammation in visceral adipose tissue from morbidly obese individuals. Sci Rep. 2017 Nov 16;7(1): 15724. doi: 10.1038/ s41598- 017-15951-z. PMID: 29146976

Steinhilber D, Uydeş-Doğan BS, Topal G, Clària J, Norel X, Schebb NH, Bannenberg G. Editorial-Special issue of the 6th European Workshop on Lipid Mediators. Prostaglandins Other Lipid Mediat. 2017 Nov; 133:1-3. doi: 10.1016/ j.prostaglandins.2017.10.005. Epub 2017 Nov 4. No abstract available. PMID: 29113951

Lehmann JM, Claus K, Jansen C, Pohlmann A, Schierwagen R, Meyer C, Thomas D, Manekeller S, Claria J, Strassburg CP, Trautwein C, Wasmuth HE, Berres ML, Trebicka J. Circulating CXCL10 in cirrhotic portal hypertension might reflect systemic inflammation and predict ACLF and mortality. Liver Int. 2018 May;38 (5):875- 884. doi: 10.1111/ liv.13610. Epub 2017 Nov 6. PMID: 29105936

Rius B, Duran-Güell M, Flores-Costa R, López-Vicario C, Lopategi A, Alcaraz-Quiles J, Casulleras M, Lozano JJ, Titos E, Clària J. The specialized proresolving lipid mediator maresin 1 protects hepatocytes from lipotoxic and hypoxia-induced endoplasmic reticulum stress. FASEB J. 2017 Dec; 31(12): 5384-5398. doi: 10.1096/ fj.201700394R. Epub 2017 Aug 2. PMID: 28768719

Clària J, López-Vicario C, Rius B, Titos E. Pro-resolving actions of SPM in adipose tissue biology. Mol Aspects Med. 2017 Dec; 58:83-92. doi: 10.1016/ j.mam.2017. 03.004. Epub 2017 Mar 25. Review. PMID: 28341541

Clària J, Stauber RE, Coenraad MJ, Moreau R, Jalan R, Pavesi M, Amorós A, Titos E, Alcaraz-Quiles J, Oettl K, Morales-Ruiz M, Angeli P, Domenicali M, Alessandria C, Gerbes A, Wendon J, Nevens F, Trebicka J, Laleman W, Saliba F, Welzel TM, Albillos A, Gustot T, Benten D, Durand F, Ginès P, Bernardi M and Arroyo V, for the CANONIC Study Investigators of the EASL-CLIF Consortium and the European Foundation for the Study of Chronic Liver Failure (EF-CLIF). Systemic inflammation in decompensated cirrhosis. Characterization and role in acute-on-chronic liver failure. Hepatology 2016; 64:1249-64.

Clària J, Arroyo V and Moreau R. The acute-on-chronic liver failure syndrome or when the innate immune system goes astray. J. Immunol. 2016:197:3755-3761.

Daniel J Klionsky et al. Guidelines for the Use and Interpretation of Assays for Monitoring Autophagy (3rd edition). Autophagy 2016; 12:1-222. 

Titos E, Rius B, López-Vicario C, García-Alonso V, Lopategi A, Alcaraz-Quiles J, Dalli J, Lozano JJ, Arroyo V, Delgado S, Serhan CN and Clària J. p38 Mitogen-Activated Protein Kinase Signals the Immuno Resolving Actions of Resolvin D1 in Inflamed Human Visceral Adipose Tissue. J Immunol 2016; 197:3360-3370.

García-Alonso V, Titos E, Alcaraz-Quiles J, Rius B, Lopategi A, López-Vicario C, Jakobsson PJ, Delgado S, Lozano J and Clària J. Prostaglandin E2 exerts multiple regulatory actions on human obese adipose tissue remodeling, inflammation, adaptive thermogenesis and lipolysis. PLos One  2016; 11:e015375.

Lopategi A, López-Vicario C, Alcaraz-Quiles J, García-Alonso V, Rius B, Titos E and Clària J. Role of bioactive lipid mediators in obese adipose tissue inflammation and endocrine dysfunction. Mol Cell Endocrinol 2016; 419:44-59

López-Vicario C, Rius B, Alcaraz-Quiles J, García-Alonso V, Lopategi A, Titos E and Clària J. Pro-resolving mediators produced from EPA and DHA: Overview of pathways involved and of their mechanisms in metabolic syndrome and related liver diseases. Eur J Pharmacol 2016:785:133-143.

Blaya D, Vila-Casadesus M, Coll M, Rodrigo-Torres D, Affò S, Altamirano J, Morales-Ibanez O, Graupera I, Perea L, Lozano JJ, Clària J, Arroyo V, Bataller R, Caballería J, Ginès P, Sancho-Bru P. Integrative MicroRNA Profiling in Alcoholic Hepatitis Reveals a Role for microRNA-182 in Liver Injury and Inflammation. Gut 2016; 65: 1535-45.

López-Vicario C, Alcaraz-Quiles J, García-Alonso V, Rius B, Hwang SE, Titos E, Lopategi A, Hammock B, Arroyo V, Clària J. Inhibition of soluble epoxide hydrolase modulates inflammation and autophagy in obese adipose tissue and liver. Role for omega-3 epoxides. Proc Natl Acad Sci USA 2015; 112:536-41.

Rius B, Titos E, Morán-Salvador E, López-Vicario C, García-Alonso V, González-Périz A, Arroyo V, Clària J. Resolvin D1 primes the resolution process initiated by calorie restriction in obesity-induced steatohepatitis. FASEB J 2014; 28:836-48

García-Alonso V and Clària J. Prostaglandin E2 signals white-to-brown adipogenic differentiation. Adipocyte 2014; 3:290-296

Spite M, Clària J and Serhan C.N. Resolvins, Specialized Pro-Resolving Lipid Mediators and their Potential Roles in Metabolic Syndrome. Cell Metab. 2014; 19:21-36

López-Vicario C, González-Périz A, Rius B, Morán-Salvador E, García-Alonso V, Lozano JJ, Bataller R, Cofán M, Kang JX, Arroyo V, Clària J, Titos E. A regulatory loop between desaturases and omega-3 fatty acids exerts protective actions in obesity-induced fatty liver disease. Gut 2014; 63:344-55

García-Alonso V, López-Vicario C, Titos E, Morán-Salvador E, González-Périz A, Rius B, Parrizas M, Werz O, Arroyo V, Clària J. Coordinate functional regulation between microsomal prostaglandin E synthase-1 and PPARγ in the conversion of white-to-brown adipocytes. J Biol Chem 2013; 288;28230-28242

Morán-Salvador E, Titos E, González-Périz A, Rius B, García-Alonso V, López-Vicario C, Miquel R, Barak Y, Arroyo V, Clària J. Cell-specific knockout mice establish anti-inflammatory and anti-fibrogenic properties for PPARg in non-parenchymal liver cells. J Hepatol 2013; 59:1045-1053

Titos E and Clària J. Omega-3-Derived Mediators Counteract Obesity-Induced Adipose Tissue Inflammation. Prostaglandins Other Lipid Mediat 2013; 107:77-84

Clària J, Nguyen BT, Madenci A, Ozaki CK, Serhan CN. Diversity of lipid mediators in human adipose tissue depots. Am J Physiol (Cell Physiol) 2013; 304:C1141-9

Noguera A, Gómez C, Faner R, Cosío B, González-Périz A, Clària J, Carvajal A, Agustí A. Investigation of the resolution of inflammation (catabasis) in COPD. Respir Res 2012; 13:101

Rius B, López-Vicario C, González-Périz A, Morán-Salvador E, García-Alonso V, Clària J, Titos E. Resolution of inflammation in obesity-induced liver disease. Front. Immunol. 2012 10.3389/fimmu.2012.00257

Clària J, Dalli J, Yacoubian S, Gao F, Serhan CN. Resolvin D1 and Resolvin D2 Govern Local Inflammatory Tone in Obese Fat. J Immunol 2012; 189:2597-2605

Titos E, González-Périz A, López-Vicario C, Rius B, Morán-Salvador E, Martínez-Clemente M, Arroyo V, Clària J. Resolvin D1 and its Precursor Docosahexaenoic Acid Promote Resolution of Adipose Tissue Inflammation by Eliciting Macrophage Polarization toward a Pro-Resolving Phenotype. J Immunol 2011; 187:5408-18

Clària J, González-Périz A, López-Vicario C, Rius B, Titos E. New Insights into the Role of Macrophages in Adipose Tissue Inflammation and Fatty Liver Disease: Modulation by Endogenous Omega-3 Fatty Acid-derived Lipid Mediators. Front. Immunol. 2011 10.3389/fimmu.2011.00049

Martínez-Clemente M, Clària J, Titos E. The 5-Lipoxygenase/Leukotriene pathway in obesity, insulin resistance and fatty liver disease. Curr Opin Clin Nutr Metab Care 2011 ;14:347-53.

Morán-Salvador, López-Parra M, García-Alonso V, Titos E, Martínez-Clemente M, González-Périz A, López-Vicario C, Barak Y, Arroyo V, Clària J. Role for PPARy in obesity-induced hepatic steatosis as determined by hepatocyte and macrophage-specific conditional knockouts. FASEB J 2011; 25:2538-50

Oliva R, Bàdenas C, Clària J, Coll MJ. Informes asistenciales en genética molecular: contenido y nomenclatura de las mutaciones. Med Clin 2011; 136:356-361.

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