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What the results are …

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Our group has made key contributions to the understanding of chronic liver disease. Selected projects (as corresponding author):

 

• Posttranscriptional reprogramming of metabolism is a driver of hepatic stellate cell activation in liver fibrosis (Gastroenterology 2020)
• Adaptive translational response to ER stress mediated by CPEB4 counteracts hepatic steatosis (Nature Cell Biology 2017)
• Vascular stem cells mediate a new mechanism responsible for formation of abnormal vessels in chronic liver disease (Gut 2017)
• CPEB proteins are critical for pathologic angiogenesis in chronic liver disease (Gastroenterology 2016)
• Endogenous angiogenesis inhibitors have potent antiangiogenic and antifibrogenic therapeutic activity in chronic liver disease (Gut 2015; Hepatology 2014)
• Angiogenesis is a critical hallmark of chronic liver disease with therapeutic potential (Journal of Hepatology 2010; Journal of Hepatology 2009; Hepatology 2009; Gut 2007; Hepatology 2007; Journal of Hepatology 2006; Journal of Hepatology 2005; Gastroenterology 2004; among many others)

 

Impact factors: Gastroenterology 20.877; Journal of Hepatology 20.582; Nature Cell Biology 20.042; Gut 19.819; Hepatology 14.679

 

Link to additional publications

Identification of dynamic RNA-binding proteins uncovers a Cpeb4-controlled regulatory cascade during pathological cell growth of cardiomyocytes

Riechert E, Kmietczyk V, Stein F, Schwarzl T, Sekaran T, Jürgensen L, Kamuf-Schenk V, Varma E, Hofmann C, Rettel M, Doroudgar S, Gür K, Ölschläger J, Kühl F, Martin J, Ramirez-Pedraza M, Fernandez M, Mendez R, Katus HA, Hentze MW, Völkers M.

Cell Reports 2021 (in press)

CPEB4 increases expression of PFKFB3 to induce glycolysis and activate mouse and human hepatic stellate cells, promoting liver fibrosis

Mejias M, Gallego J, Naranjo-Suarez S, Ramirez M, Pell N, Manzano A, Suñer C, Bartrons R, Mendez R, Fernandez M

Corresponding author: Mercedes Fernandez

Gastroenterology 2020; 159: 273-288.

This paper has been highlighted in the Covering the Cover section of Gastroenterology: CPEB4-induced expression of PFKFB3 promotes liver fibrosis. Gastroenterology 2020; 159: 5. 

Crosstalk between angiogenesis and fibrogenesis in liver disease

Mejias M, Balvey A, Fernandez M

Corresponding author: Mercedes Fernandez

Current Tissue Microenvironment Reports 2020; 1: 121-129; Springer Nature.

Recent advances in practical methods for liver cell biology: A short overview

Torres S,  Abdullah Z,  Brol MJ, Hellerbrand C, Fernandez M, Fiorotto R, Klein S, Königshofer P, Liedtke C, Lotersztajn S, Nevzorova YA, Schierwagen R, Reiberger T, Uschner FE, Tacke F, Weiskirchen R, Trebicka J

International Journal of Molecular Sciences 2020; 21(6), 2027; doi:10.3390/ijms21062027

Section Molecular Pathology, Diagnostics, and Therapeutics (ISSN 1422-0067)

Crucial role of beta-arrestin-2 in linking fibrogenesis and cancer

Schierwagen R, Dietrich P, Heinzen J, Klen S, Uschner F, Ortiz C, Tyc O, Torres S, Rathmann S, Premont R, Poisson J, Rautou PE, Kristiansen G, Gracia J, Poglitsch M, Ludwig-Portugall I, Walther T, Abdullah Z, Lefkowitz R, Fernandez M, Moreau R, Hellerbrand C, Rombouts K, Kastenmüller W, Diehl AM, Trebicka J.

Journal of Hepatology 2020; 73, S58-S98

Interplay between macrophages and angiogenesis: A double-edged sword in liver disease

Ramirez-Pedraza M, Fernandez M

Corresponding author: Mercedes Fernandez

Frontiers in Immunology 2019; 10:2882 (doi.org/10.3389/fimmu.2019.02882)

Section Molecular Innate Immunity. Editor Ralf Weiskirchen. Open Access Article 

Invited Review

CPEB4-driven PFKFB3-mediated metabolic reprogramming is essential for hepatic stellate cell activation and liver fibrosis: A novel druggable target

Mejias M, Gallego J, Naranjo-Suarez S, Ramirez M, Pell N, Manzano A, Bartrons R, Mendez R, Fernandez M

Corresponding author: Mercedes Fernandez

Hepatology 2019; 70 (Suppl):1444A

This abstract has been selected as a Presidential Poster of Distinction by the American Association for the Study of Liver Disease (AASLD). Posters of Distinction are classified as being in the top 10% of all accepted poster abstracts and receive special recognition in the Poster Hall. It has been presented in the Basic Fibrosis Research and Stellate Cell Biology Session, at The Liver Meeting 2019 (Boston, Massachusetts).

This abstract has also been selected by the AASLD Liver Fibrosis Special Interest Group to be presented as an oral communication at the TechBar of the Liver Meeting 2019.

Pathological angiogenesis: The new culprit behind chronic liver disease

Ramirez M, Fernandez M

Corresponding author: Mercedes Fernandez

OBM Hepatology and Gastroenterology 2019; 3:15 (doi:10.21926/obm.hg.1903030), Special Issue: “Exploring Novel Treatment Options for Liver Fibrosis: Can Anti-Angiogenics Succeed?”. Ed. M. Bartneck. Lidsen Publishing, Ohio, USA. Link

Invited Review

Pericytes in the gut

Ramirez M, Pell N, Mejias M, Fernandez M

Co-first authors: Marta Ramirez and Nuria Pell

Corresponding author: Mercedes Fernandez

Advances in Experimental Medicine and Biology 2019; 1122:73-100, “Pericyte Biology in Different Organs”, Ed. A. Birbrair. Springer Nature, Switzerland AG 

Invited Review

Role of ductular reaction on the hepatic microenvironment in chronic liver disease

Molecular and cellular mechanisms of neovascularization in portal hypertension and cirrhosis

Garcia-Pras E

Thesis Director: Mercedes Fernandez

Doctoral Thesis – University of Barcelona 2018

Regulatory mechanisms of VEGF-dependent angiogenesis in portal hypertension and cirrhosis

Gallego J

Thesis Director: Mercedes Fernandez

Doctoral Thesis – University of Barcelona 2018

Placental growth factor: New treatment target bringing hope in hepatopulmonary syndrome

Fernandez M

Corresponding author: Mercedes Fernandez

Hepatology 2018; 68:404-407 

Invited Editorial

Protective role of VEGF-A165b in liver cirrhosis with portal hypertension

Schierwagen R, Lehmann J, Ruiner C, Pohlmann A, Jansen F, Klein S, Uschner F, Magdaleno F, Fernandez M, Berres M, Rautou P, Trebicka T

Z Gastroenterol 2018; 56:E2-E89 (DOI: 10.1055/s-0037-1612662)  

Ductular reaction cells promote angiogenesis via SLIT2/ROBO1 pathway in chronic liver disease

Coll M, Garcia-Pras E, Aguilar-Bravo B, Gallego J, Blaya D, Vallverdu J, Perea L, Graupera I, Pose E, Lozano J, Bataller R, Gines P, Geng JG, Fernandez M, Sancho-Bru P

Journal of Hepatology 2018; 68: S92

This abstract has been presented as Oral Communication at the International Liver Congress of the European Association for the Study of the Liver (EASL) (Paris, France, 2018).  

Circadian- and UPR-dependent control of CPEB4 mediates a translational response to counteract hepatic steatosis under ER stress

Maillo C, Martin J, Sebastian D, Hernandez-Alvarez M, Garcia-Rocha M, Reina O, Zorzano A, Fernandez M, Mendez R

Co-corresponding authors: Raul Mendez and Mercedes Fernandez

Nature Cell Biology 2017; 19:94-105

Comment on this paper: Moore PC & Oakes SA. CPEB4 links the clock and the UPR to protect the liver. Nature Cell Biology (2017);19:79-81. Comment

This paper received the Award to the Best Scientific Publication (Year 2018) from the Spanish Association Against Cancer (AECC) 

Therapeutic siRNA targeting endothelial KDR decreases portosystemic collateralization in portal hypertension

Gallego J, Garcia-Pras E, Mejias M, Pell N, Schaeper U, Fernandez M

Co-first authors: Javier Gallego and Ester Garcia-Pras

Corresponding author: Mercedes Fernandez

Scientific Reports 2017; 7:14791-14806  PubMed    Springer Nature SharedIt

Gene therapy with endothelial-specific liposomal short interfering siRNA targeting kinase insert domain receptor inhibits portosystemic collateralization in portal hypertension

Gallego J, Garcia-Pras E, Mejias M, Pell N, Schaeper U, Fernandez M

Corresponding author: Mercedes Fernandez

Hepatology 2017; 66:141A

This abstract has been presented in Parallel Session at the Annual Meeting of the American Association for the Study of Liver Disease (AASLD) (Washington DC, 2017). The speaker and coauthor, Nuria Pell, has been awarded with the 2017 Basic Science Young Investigator Travel Award from AASLD, which recognizes outstanding young basic science researchers working on liver disease. 

Role and therapeutic potential of vascular stem/progenitor cells in pathological neovascularisation during chronic portal hypertension

Garcia-Pras E, Gallego J, Coch L, Mejias M, Fernandez-Miranda G, Pardal R, Bosch J, Mendez R, Fernandez M

Corresponding author: Mercedes Fernandez

Gut 2017; 66:1306-1320 PubMed

Gastroesophageal varices

Fernandez M, Abraldes JG

Corresponding author: Mercedes Fernandez

In: Liver Pathophysiology: Therapies & Antioxidants 2017; Ed. Muriel P, Academic Press, Elsevier (ISBN: 978-0-12-804274-8)

Invited Review

Sequential functions of CPEB1 and CPEB4 regulate pathologic expression of VEGF and angiogenesis in chronic liver disease

Calderone V, Gallego J, Fernandez-Miranda G, Garcia-Pras E, Maillo C, Berzigotti A, Mejias M, Bava FA, Angulo-Urarte A, Graupera M, Navarro P, Bosch J, Fernandez M, Mendez R

Co-first authors: Vittorio Calderone and Javier Gallego

Co-corresponding authors: Raul Mendez and Mercedes Fernandez

Gastroenterology 2016;150:982-997  PubMed

Pathogenesis of portal hypertension: Extrahepatic mechanisms

Fernandez M, Mejias M, Garcia-Pras E, Gallego J, Pell N, Ramirez M, Naranjo-Suarez S, Barrachina-Catala A 

Corresponding author: Mercedes Fernandez

Current Hepatology Reports 2016;15:199-207   

Invited Review

Molecular pathophysiology of portal hypertension

Fernandez M 

Corresponding author: Mercedes Fernandez

Hepatology 2015; 61:1406-1415 PubMed

Invited Review

Antiangiogenic and antifibrogenic activity of pigment epithelium-derived factor (PEDF) in bile duct-ligated portal hypertensive rats

Mejias M, Coch L, Berzigotti A, Garcia-Pras E, Gallego J, Bosch J, Fernandez M

Corresponding author: Mercedes Fernandez

Gut 2015; 64:657-666 PubMed

Editorial devoted to this article: Vespasiani-Gentilucci U, Rombouts K. Boosting pigment epithelial-derived factor: a promising approach for the treatment of early portal hypertension. Gut (2015) 64:523-524 Editorial

Disruption of negative feedback loop between vasohibin-1 and vascular endothelial growth factor decreases portal pressure, angiogenesis, and fibrosis in cirrhotic rats

Coch L, Mejias M, Berzigotti A, Garcia-Pras E, Gallego J, Bosch J, Mendez R, Fernandez M

Corresponding author: Mercedes Fernandez

Hepatology 2014; 60:633-647 PubMed

Editorial devoted to this article: Chatterjee S. Reversal of vasohibin-driven negative feedback loop of vascular endothelial growth factor/angiogenesis axis promises a novel antifibrotic therapeutic strategy for liver diseases. Hepatology (2014) 60:458-460 Editorial

Hepatology Highlights devoted to this article: Dufour JF. After vasopressin comes vasohibin. Hepatology (2014) 60:447 Highlights

Effects of the combined administration of propranolol plus sorafenib on portal hypertension in cirrhotic rats

D’Amico M, Mejias M, Garcia-Pras E, Abraldes JG, Garcia-Pagan JC, Fernandez M, Bosch J

American Journal of Physiology 2012;302:G1191-G1198 PubMed

Unveiling a new mechanism of regulation of angiogenesis in portal hypertension through translational control by the CPEB family of proteins

Gallego J, Calderone V, Garcia-Pras E, Bosch J, Mendez R, Fernandez M

Corresponding author: Mercedes Fernandez

Journal of Hepatology 2012; 56:S53

This abstract has been presented at the International Liver Congress of the European Association for the Study of the Liver (EASL) (Barcelona, Spain, 2012)

Relevance of the mTOR signaling pathway in the pathophysiology of splenomegaly in rats with chronic portal hypertension

Mejias M, Garcia-Pras E, Gallego J, Mendez R, Bosch J, Fernandez M

Corresponding author: Mercedes Fernandez

Journal of Hepatology 2010; 52:529-539 PubMed

Hepatic endothelial dysfunction and abnormal angiogenesis: New targets in the treatment of portal hypertension

Bosch J, Abraldes JG, Fernandez M, Garcia-Pagan JC

Journal of Hepatology 2010; 53:558-567 PubMed

Effects of the combined administration of sorafenib plus propranolol on portal hypertension in cirrhotic rats

D’Amico M, Mejias M, Garcia-Pras E, Abraldes J, Garcia-Pagan JC, Fernandez M, Bosch J

Journal of Hepatology 2010; 52:S203

This abstract has been presented at the International Liver Congress of the European Association for the Study of the Liver (EASL) (Vienna, Austria, 2010)

Beneficial effects of sorafenib on splanchnic, intrahepatic, and portocollateral circulations in portal hypertensive and cirrhotic rats

Mejias M, Garcia-Pras E, Tiani C, Miquel R, Bosch J, Fernandez M

Corresponding author: Mercedes Fernandez

Hepatology 2009;49:1245-1256 PubMed

Editorial devoted to this article: Shah VH, Bruix J. Antiangiogenic therapy: not just for cancer anymore? Hepatology (2009) 49:1066-1068 Editorial

Apelin signaling modulates splanchnic angiogenesis and portosystemic collateral vessel formation in rats with portal hypertension

Tiani C, Garcia-Pras E, Mejias M, de Gottardi A, Berzigotti A, Bosch J, Fernandez M

Corresponding author: Mercedes Fernandez

Journal of Hepatology 2009; 50:296-305 PubMed

Angiogenesis in liver disease

Fernandez M, Semela D, Bruix J, Colle I, Pinzani M, Bosch J

Journal of Hepatology 2009; 50:604-620 PubMed

As of September 2018, this “Highly Cited Paper” received enough citations (315) to place it in the top 1% of its academic field based on a highly cited threshold for the field and publications year. Data from Essential Science Indicators.

Impacto de los inhibidores de la angiogénesis en el tratamiento de la hipertensión portal

Fernandez M

Corresponding author: Mercedes Fernandez

Gastroenterología y Hepatología Continuada 2009;8:312-317

Invited Review

Bone morphogenetic proteins (BMP) and BMP signalling are significantly increased in experimental models of cirrhosis and portal hypertension

De Gottardi A, Mejias M, Garcia-Pras E, Rodriguez-Vilarrupla A, Garcia-Pagan JC, Fernandez M, Bosch J

Journal of Hepatology 2009; 50:S17

This abstract has been presented at the International Liver Congress of the European Association for the Study of the Liver (EASL) (Copenhagen, Denmark, 2009)

The somatostatin analogue octreotide inhibits angiogenesis in the earliest, but not in advanced, stages of portal hypertension in rats

Mejias M, Garcia-Pras E, Tiani C, Bosch J, Fernandez M

Corresponding author: Mercedes Fernandez

Journal of Cellular and Molecular Medicine 2008;12: 1690-1699 PubMed

Role of angiogenesis in portal hypertension

Fernandez M, Mejias M, Garcia-Pras E, Bosch J

Corresponding author: Mercedes Fernandez

In: Liver Cirrhosis: From Pathophysiology to Disease Management 2008; Edited by: Bosch J, Burroughs AK, Lammert F, Sauerbruch T, Lebrec D. Springuer, Dordrecht, The Netherlands. Volume 162, pages 112-129

Invited Review

Reversal of portal hypertension and hyperdynamic splanchnic circulation by combined vascular endothelial growth factor and platelet-derived growth factor blockade in rats

Fernandez M, Mejias M, Garcia-Pras E, Mendez R, Garcia-Pagan JC, Bosch J

Corresponding author: Mercedes Fernandez

Hepatology 2007;46:1208-1217 PubMed

This paper received the Award to the Best Publication in Hepatology Research (Year 2007), from the Spanish Association for the Study of the Liver

NAD(P)H oxidase modulates angiogenesis and the development of portosystemic collaterals and splanchnic hyperaemia in portal hypertensive rats

Angermayr B, Fernandez M, Mejias M, Gracia-Sancho J, Garcia-Pagan JC, Bosch J

Corresponding author: Mercedes Fernandez

Gut 2007;56:560-564 PubMed

The somatostatin analogue octreotide inhibits angiogenesis and VEGF expression in early, but not late, stages of portal hypertension in rats. Role of somatostatin receptor subtype 2 downregulation during the evolution of the portal hypertensive syndrome

Mejias M, Garcia-Pras E, Bosch J, Fernandez M

Corresponding author: Mercedes Fernandez

Hepatology 2007; 46:607A

This abstract has been presented at the Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) (Boston, MA, US, 2007)

Heme oxygenase attenuates oxidative stress and inflammation, and increases VEGF expression in portal hypertensive rats

Angermayr B, Mejias M, Gracia-Sancho J, Garcia-Pagan JC, Bosch J, Fernandez M 

Corresponding author: Mercedes Fernandez

Journal of Hepatology 2006; 44:1033-1039 PubMed

NAD(P)H oxidase modulates angiogenesis and the development of portosystemic collaterals and splanchnic hyperemia in portal hypertensive rats

Angermayr B, Fernandez M, Mejias M, Gracia-Sancho J, Garcia-Pagan JC, Bosch J

Corresponding author: Mercedes Fernandez

Hepatology 2006; 44:358A

This abstract has been presented at the Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) (Boston, MA, US, 2006)

Inhibition of VEGF receptor-2 decreases the development of hyperdynamic splanchnic circulation and portal-systemic collateral vessels in portal hypertensive rats

Fernandez M, Mejias M, Angermayr B, Garcia-Pagan JC, Rodes J, Bosch J 

Corresponding author: Mercedes Fernandez

Journal of Hepatology 2005; 43:98-103 PubMed

Editorial devoted to this article: Moreau R. “VEGF-induced angiogenesis drives collateral circulation in portal hypertension”. J Hepatol 2005;43:6-8 Editorial

Carbon monoxide and the heme oxygenase system in cirrhosis

Lambrecht RW, Fernandez M, Shan Y, Bonkovsky HL

In: Ascites and Renal Dysfunction in Liver Disease. Pathogenesis, diagnosis and treatment 2005. Edited by: Gines P, Arroyo V, Rodes J, Schrier RW. Blackwell Publishing Ltd, Oxford, United Kingdom. Pg. 125-136

Invited Review

Oxidative stress contributes to the hyperdynamic circulation in portal hypertensive rats

Angermayr B, Mejias M, Garcia-Pagan JC, Rodes J, Bosch J, Fernandez M

Corresponding author: Mercedes Fernandez

Journal of Hepatology 2005; 42:63

This abstract has been presented at the International Liver Congress of the European Association for the Study of the Liver (EASL) (Paris, France, 2005)

Anti-VEGF receptor-2 monoclonal antibody prevents portal-systemic collateral vessel formation in portal hypertensive mice

Fernandez M, Vizzutti F, Garcia-Pagan JC, Rodes J, Bosch J

Corresponding author: Mercedes Fernandez

Gastroenterology 2004; 126:886-894 PubMed

Contribution of heme oxygenase to the splanchnic hyperdynamic circulation in portal hypertensive rats: Interaction with nitric oxide synthase

Angermayr B, Fernandez M, Mejias M, Garcia-Pagan JC, Rodes J, Bosch J

Corresponding author: Mercedes Fernandez

Hepatology 2004; 40:484A

This abstract has been presented at the Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) (Boston, MA, US, 2004)

Inhibition of VEGF receptor-2 (VEGFR-2) signaling prevents portal-systemic collateral (PSC) vessel formation in rats with portal hypertension

Fernandez M, Mejias M, Angermayr B, Garcia-Pagan JC, Rodes J, Bosch J

Corresponding author: Mercedes Fernandez

Journal of Hepatology 2004; 40:4

This abstract has been presented at the International Liver Congress of the European Association for the Study of the Liver (EASL) (Berlin, Germany, 2004)

Heme oxygenase protects against oxidative stress, inflammation, and inflammatory angiogenesis in portal hypertension

Angermayr B, Fernandez M, Mejias M, March S, Gracia-Sancho J, Garcia-Pagan JC, Rodes J, Bosch J

Corresponding author: Mercedes Fernandez

Hepatology 2004; 40:480A

This abstract has been presented at the Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) (Boston, MA, US, 2004)

Vascular endothelial growth factor increases heme oxygenase-1 expression in the chicken embryo chorioallantoic membrane 

Fernandez M, Bonkovsky HL

Corresponding author: Mercedes Fernandez

British Journal of Pharmacology 2003; 139:634-640 PubMed

Increased heme oxygenase activity in splanchnic organs from portal hypertensive rats: Role in modulating mesenteric vascular reactivity 

Fernandez M, Lambrecht RW, Bonkovsky HL

Corresponding author: Mercedes Fernandez

Journal of Hepatology 2001; 34:812-817 PubMed

Editorial devoted to this article: Moreau R. Heme oxygenase: protective enzyme or portal hypertensive molecule?. Journal of Hepatology (2001) 34:936-939 Editorial

Role of increased heme oxygenase activity on splanchnic vascular hyporeactivity in portal hypertensive rat

Fernandez M, Lambrecht RW, Bonkovsky HL

Corresponding author: Mercedes Fernandez

FASEB Journal 2000; 14:A1390

This abstract has been presented at the Meeting of the American Society for Biochemistry and Molecular Biology and the American Society for Pharmacology and Experimental Therapeutics (ASBMS/ ASPET) (Boston, MA, US, 2000)

Increased heme oxygenase-1 gene expression in liver cells and splanchnic organs from portal hypertensive rats

Fernandez M, Bonkovsky HL

Corresponding author: Mercedes Fernandez

Hepatology 1999; 29:1672-1679 PubMed

Induction of heme oxygenase (HO) in hepatocytes splanchnic organs in portal hypertensive rats: Expression of constitutive HO in hepatic stellate cells

Fernandez M, Bonkovsky HL

Corresponding author: Mercedes Fernandez

Hepatology 1998; 28:509A

This abstract has been presented at the Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) (Chicago, Illinois, US, 1998)