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What the results are …


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

  • Targeting the cytoplasmic polyadenylation element binding protein CPEB4 protects against diet-induced obesity and microbiome dysbiosis (Molecular Metabolism 2021)

  • Posttranscriptional reprogramming of metabolism is a driver of hepatic stellate cell activation in liver fibrosis (Gastroenterology 2020)

  • Transient CPEB4 overexpression upon high fat diet is required to resolve hepatic endoplasmic reticulum stress and restore metabolic homeostasis through adaptive responses (Nature Cell Biology 2017)

  • CPEB proteins are overexpressed in protumorigenic regenerative micronodules of human cirrhotic livers (Gastroenterology 2016)

  • CPEB proteins promote pathologic angiogenesis and vasculogenesis, hallmarks of chronic liver disease that increase tumorigenicity and aggresiveness of liver cancer (Gastroenterology 2016; Gut 2017)

  • 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 23.936; Journal of Hepatology 25.083; Nature Cell Biology 26.648; Gut 23.059; Hepatology 17.425; Cell Reports 9.423; Molecular Metabolism 7.422


Link to additional publications

Targeting the cytoplasmic polyadenylation element binding protein CPEB4 protects against diet-induced obesity and microbiome dysbiosis

Pell N, Garcia-Pras E, Gallego J, Naranjo-Suarez S, Balvey A, Suñer C, Fernandez-Alfara M, Chanes V, Carbo J, Ramirez-Pedraza M, Reina O, Thingholm L, Bang C, Rühlemann M, Franke A, Schierwagen R, Rheinwalt KP, Trebicka J, Mendez R, Fernandez M. 

Molecular Metabolism 2021; 54: 101388 (https://doi.org/10.1016/j.molmet.2021.101388) 

Corresponding author: Mercedes Fernandez

Translational control in liver disease

Balvey A, Fernandez M. 

Frontiers of Physiology 2021; https://doi.org/10.3389/fphys.2021.795298.  

Corresponding author: Mercedes Fernandez

Ductular reaction promotes intrahepatic angiogenesis via Slit2-Robo1 signaling

Coll M, Ariño S, Mártinez-Sánchez C, Garcia-Pras E, Gallego J, Moles A, Aguilar-Bravo B, Blaya D, Vallverdú J, Rubio-Tomás T, Lozano JJ, Pose E, Graupera I, Fernández-Vidal A, Pol A, Bataller R, Geng JG, Ginès P, Fernandez M, Sancho-Bru P.

Hepatology 2021; doi: 10.1002/hep.32140.  

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; 35 (6): 109100. 

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 2020159: 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

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

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

Fernandez M

Corresponding author: Mercedes Fernandez

Hepatology 201868:404-407 

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)  

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. 

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 20177:14791-14806 

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

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-corresponding authors: Raul Mendez and Mercedes Fernandez

Gastroenterology 2016;150:982-997 

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 201561:1406-1415 

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 201564:657-666

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 

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 201460:633-647

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 

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

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

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 201052:529-539

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 201053:558-567 

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

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

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 200950:296-305 

Angiogenesis in liver disease

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

Journal of Hepatology 200950:604-620

As of September 2020, this “Highly Cited Paper” received enough citations (401 citations) 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

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 2008Edited 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 

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

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

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

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

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

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

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

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 

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

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 

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