Research Groups

Andres Muro

Mouse Molecular Genetics

Group Leader

Research Interests and Description
Group Members

Andrés Fernando Muro

International Centre for Genetic Engineering and Biotechnology
Padriciano 99
34149 Trieste, Italy

E-mail: muroicgeb.org
Office tel: +39-040-3757369
Lab tel: +39-040-3757312
Office fax: +39-040-226555

Education

School of Sciences, University of Buenos Aires, Buenos Aires, Argentina, PhD in Biology, 1992
School of Sciences, University of Buenos Aires, Buenos Aires, Argentina, MSc in Molecular Biology, 1988

Career History

Since 2005, Group Leader of the Mouse Molecular Genetics Laboratory of the International Centre of Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy.
1995-2004, Staff Scientist, Molecular Pathology Laboratory, ICGEB, Trieste, Italy.
1992-1994, Postdoc, Molecular Pathology Laboratory, ICGEB, Trieste, Italy.
1991, Visiting scientist, Molecular Pathology Laboratory, ICGEB, Trieste, Italy.
1988-1992, Graduate Student Fellowship, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) at the Instituto de Ingenieria Genetica y Biologia Molecular (INGEBI-CONICET), Buenos Aires, Argentina.
1987-1988, Pre-doctoral student at Laboratorio de Biologia Molecular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina.

Scientific Activity

Dr. Muro's main focus of research is the understanding of gene function and their relation to diseases, and the development of efficient therapeutic approaches, using mouse models, with special emphasis in metabolic liver diseases, in particular in the study of the mechanisms of disease and possible therapies of neonatal hyperbilirubinemia and the Crigler-Najjar syndrome type I. He is interested in the understanding of the mechanisms of bilirubin neurotoxicity, in order to develop pharmacological and gene therapy approaches aimed to avoid severe and permanent brain damage, and lethality.
In parallel to the work in CNSI, he is developing a therapeutic vector to treat patients suffering from ornithine transcarbamylase deficiency.
Dr. Muro is participating in international research and clinical networks aiming to transfer the developed therapies to the clinics.
Research activity is supported through grants from public and private agencies, including the Telethon, Genethon, and the European Commission (H2020), as well as through collaborations with companies (Selecta Biosciences, US).

Selected publications

Bortolussi G, Muro AF. 2018. Advances in understanding disease mechanisms and potential treatments for Crigler–Najjar syndrome. Expert Opinion on Orphan Drugs 6:425-439.

Vodret S, Bortolussi G, Iaconcig A, Martinelli E, Tiribelli C, Muro AF. 2018. Attenuation of neuro-inflammation improves survival and neurodegeneration in a mouse model of severe neonatal hyperbilirubinemia. Brain Behav Immun 70:166-178.

Bockor L, Bortolussi G, Iaconcig A, Chiaruttini G, Tiribelli C, Giacca M, Benvenuti F, Zentilin L, Muro AF. 2017a. Repeated AAV-mediated gene transfer by serotype switching enables long-lasting therapeutic levels of hUgt1a1 enzyme in a mouse model of Crigler-Najjar Syndrome Type I. Gene Ther 24:649-660.

Bockor L, Bortolussi G, Vodret S, Iaconcig A, Jasprova J, Zelenka J, Vitek L, Tiribelli C, Muro AF. 2017b. Modulation of bilirubin neurotoxicity by the Abcb1 transporter in the Ugt1-/- lethal mouse model of neonatal hyperbilirubinemia. Hum Mol Genet 26:145-157.

Porro F, Bortolussi G, Barzel A, De Caneva A, Iaconcig A, Vodret S, Zentilin L, Kay MA, Muro AF. 2017. Promoterless gene targeting without nucleases rescues lethality of a Crigler-Najjar syndrome mouse model. EMBO Mol Med 9:1346-1355.

Vodret S, Bortolussi G, Jasprova J, Vitek L, Muro AF. 2017. Inflammatory signature of cerebellar neurodegeneration during neonatal hyperbilirubinemia in Ugt1 (-/-) mouse model. J Neuroinflammation 14:64.

Malara A, Gruppi C, Celesti G, Romano B, Laghi L, De Marco L, Muro AF, Balduini A. 2016. Brief Report: Alternative Splicing of Extra Domain A (EIIIA) of Fibronectin Plays a Tissue-Specific Role in Hematopoietic Homeostasis. Stem Cells 34:2263-2268.

Ronzitti G, Bortolussi G, van Dijk R, Collaud F, Charles S, Leborgne C, Vidal P, Martin S, Gjata B, Sola MS, van Wittenberghe L, Vignaud A, Veron P, Bosma PJ, Muro AF, Mingozzi F. 2016. A translationally optimized AAV-UGT1A1 vector drives safe and long-lasting correction of Crigler-Najjar syndrome. Mol Ther Methods Clin Dev 3:16049.

Bortolussi G, Codarin E, Antoniali G, Vascotto C, Vodret S, Arena S, Cesaratto L, Scaloni A, Tell G, Muro AF. 2015. Impairment of enzymatic antioxidant defenses is associated with bilirubin-induced neuronal cell death in the cerebellum of Ugt1 KO mice. Cell Death Dis 6:e1739.

Pulakazhi Venu VK, Uboldi P, Dhyani A, Patrini A, Baetta R, Ferri N, Corsini A, Muro AF, Catapano AL, Norata GD. 2015. Fibronectin extra domain A stabilises atherosclerotic plaques in apolipoprotein E and in LDL-receptor-deficient mice. Thromb Haemost 114:186-197.

Vodret S, Bortolussi G, Schreuder AB, Jasprova J, Vitek L, Verkade HJ, Muro AF. 2015. Albumin administration prevents neurological damage and death in a mouse model of severe neonatal hyperbilirubinemia. Sci Rep 5:16203.

Bortolussi G, Baj G, Vodret S, Viviani G, Bittolo T, Muro AF. 2014. Age-dependent pattern of cerebellar susceptibility to bilirubin neurotoxicity in vivo in mice. Dis Model Mech 7:1057-1068.

Danussi C, Del Bel Belluz L, Pivetta E, Modica TM, Muro A, Wassermann B, Doliana R, Sabatelli P, Colombatti A, Spessotto P. 2013. EMILIN1/alpha9beta1 integrin interaction is crucial in lymphatic valve formation and maintenance. Mol Cell Biol 33:4381-4394.

Nedeljkovic M, Costessi L, Iaconcig A, Porro F, Muro AF. 2013. Long-distance regulation of Add2 pre-mRNA3'end processing. RNA Biol 10:516-527.

Booth AJ, Wood SC, Cornett AM, Dreffs AA, Lu G, Muro AF, White ES, Bishop DK. 2012. Recipient-derived EDA fibronectin promotes cardiac allograft fibrosis. J Pathol 226:609-618.

Bortolussi G, Zentilin L, Baj G, Giraudi P, Bellarosa C, Giacca M, Tiribelli C, Muro AF. 2012. Rescue of bilirubin-induced neonatal lethality in a mouse model of Crigler-Najjar syndrome type I by AAV9-mediated gene transfer. FASEB J 26:1052-1063.

Kohan M, Muro AF, White ES, Berkman N. 2010. EDA-containing cellular fibronectin induces fibroblast differentiation through binding to alpha4beta7 integrin receptor and MAPK/Erk 1/2-dependent signaling. FASEB J 24:4503-4512.

Morgan M, Iaconcig A, Muro AF. 2010. CPEB2, CPEB3 and CPEB4 are coordinately regulated by miRNAs recognizing conserved binding sites in paralog positions of their 3'-UTRs. Nucleic Acids Res 38:7698-7710.

Porro F, Rosato-Siri M, Leone E, Costessi L, Iaconcig A, Tongiorgi E, Muro AF. 2010. beta-adducin (Add2) KO mice show synaptic plasticity, motor coordination and behavioral deficits accompanied by changes in the expression and phosphorylation levels of the alpha- and gamma-adducin subunits. Genes Brain Behav 9:84-96.

White ES, Sagana RL, Booth AJ, Yan M, Cornett AM, Bloomheart CA, Tsui JL, Wilke CA, Moore BB, Ritzenthaler JD, Roman J, Muro AF. 2010. Control of fibroblast fibronectin expression and alternative splicing via the PI3K/Akt/mTOR pathway. Exp Cell Res 316:2644-2653.

Bazigou E, Xie S, Chen C, Weston A, Miura N, Sorokin L, Adams R, Muro AF, Sheppard D, Makinen T. 2009. Integrin-alpha9 is required for fibronectin matrix assembly during lymphatic valve morphogenesis. Dev Cell 17:175-186.

Chauhan AK, Kisucka J, Cozzi MR, Walsh MT, Moretti FA, Battiston M, Mazzucato M, De Marco L, Baralle FE, Wagner DD, Muro AF. 2008. Prothrombotic effects of fibronectin isoforms containing the EDA domain. Arterioscler Thromb Vasc Biol 28:296-301.

Muro AF, Moretti FA, Moore BB, Yan M, Atrasz RG, Wilke CA, Flaherty KR, Martinez FJ, Tsui JL, Sheppard D, Baralle FE, Toews GB, White ES. 2008. An essential role for fibronectin extra type III domain A in pulmonary fibrosis. Am J Respir Crit Care Med 177:638-645.

White ES, Baralle FE, Muro AF. 2008. New insights into form and function of fibronectin splice variants. J Pathol 216:1-14.

Moretti FA, Chauhan AK, Iaconcig A, Porro F, Baralle FE, Muro AF. 2007. A major fraction of fibronectin present in the extracellular matrix of tissues is plasma-derived. J Biol Chem 282:28057-28062.

Costessi L, Devescovi G, Baralle FE, Muro AF. 2006. Brain-specific promoter and polyadenylation sites of the beta-adducin pre-mRNA generate an unusually long 3'-UTR. Nucleic Acids Res 34:243-253.

Fededa JP, Petrillo E, Gelfand MS, Neverov AD, Kadener S, Nogues G, Pelisch F, Baralle FE, Muro AF, Kornblihtt AR. 2005. A polar mechanism coordinates different regions of alternative splicing within a single gene. Mol Cell 19:393-404.

Buratti E, Muro AF, Giombi M, Gherbassi D, Iaconcig A, Baralle FE. 2004. RNA folding affects the recruitment of SR proteins by mouse and human polypurinic enhancer elements in the fibronectin EDA exon. Mol Cell Biol 24:1387-1400.

Muro AF, Chauhan AK, Gajovic S, Iaconcig A, Porro F, Stanta G, Baralle FE. 2003. Regulated splicing of the fibronectin EDA exon is essential for proper skin wound healing and normal lifespan. J Cell Biol 162:149-160.

Yang H, Francis SC, Sellers K, DeBarros M, Sun C, Sumners C, Ferrario CM, Katovich MJ, Muro AF, Raizada MK. 2002. Hypertension-linked decrease in the expression of brain gamma-adducin. Circ Res 91:633-639.

Muro AF, Marro ML, Gajovic S, Porro F, Luzzatto L, Baralle FE. 2000. Mild spherocytic hereditary elliptocytosis and altered levels of alpha- and gamma-adducins in beta-adducin-deficient mice. Blood 95:3978-3985.

Marro ML, Scremin OU, Jordan MC, Huynh L, Porro F, Roos KP, Gajovic S, Baralle FE, Muro AF. 2000. Hypertension in beta-adducin-deficient mice. Hypertension 36:449-453.

Muro AF, Caputi M, Pariyarath R, Pagani F, Buratti E, Baralle FE. 1999. Regulation of fibronectin EDA exon alternative splicing: possible role of RNA secondary structure for enhancer display. Mol Cell Biol 19:2657-2671.

 

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