SRF

GENETICS AND PHYSIOPATHOLOGY OF MUSCLE TISSUES

Université Pierre et Marie Curie

CNRS UMR 8256

INSERM ERL U1164

Zhenlin LI : 33 (1) 44 27 21 36 / Zhenlin.li@upmc.fr
Mathias MERICSKAY : 33 (1) 44 27 26 45 / mathias.mericskay@upmc.fr

Research interests

The group “Genetics and physiopathology of muscle tissues” focuses on the cellular and molecular mechanisms involved in the cardiovascular system and skeletal muscle age-associated diseases.
In the previous years, we focused on two main models, a conditional KO of the SRF transcription factor regulating muscle genes in cardiovascular tissues and we pursued our study on the role of intermediate filaments (IFs) in muscle through the generation of a new KO model for synemin, a partner of desmin.
We have studied extensively the molecular mechanisms underlying the pathogenesis of cardiovascular and skeletal muscle diseases including, dilated cardiomyopathy and heart failure, angiogenesis, muscle dystrophy and wasting.
Aging is characterized by an increased prevalence and severity of these diseases. We will take advantage of our expertise in the study of these diseases and of our available mouse models, to evolve toward the field of aging biology with a focus on the regulation of gene expression, cytoskeleton organization and energy metabolism in muscle tissues during aging process which has become a major health and social concern given the aging of the population.
Aging is characterized by a progressive functional and structural decline in multiple organs including muscle tissues. In the aging heart, there is a loss of total number of cardiomyocytes and hypertrophy of remnant cardiomyocytes associated with increased fibrosis that increases ventricular wall stiffness and risk of arrhythmia. Aged skeletal muscles are characterized by fiber atrophy, loss of regenerative potential and weakness (sarcopenia) while the fat/lean mass ratio tends to gradually increase with age (sarcopenic obesity). Several postulated mechanisms for aging include mitochondrial dysfunction, telomere loss, altered gene expression, cumulative DNA damage, autophagy dysfunction and increased production of intracellular reactive oxygen species. Reduced oxidative phosphorylation and subsequent decline in ATP generation in elderly humans suggest a fundamental role of mitochondria and energy maintenance in the muscle aging process. Aging is also contributing to insulin resistance in muscle.
A key aspect of energy metabolism in muscle tissues is the complex interaction between the cytoskeleton and the energy units formed by mitochondria, glycolytic complexes and energy transfer systems such as the phosphocreatine shuttle. Indeed muscle is consuming enormous amount of energy and the intracellular energy units are spatially organized in the cell to deliver ATP at the right place. This coupling is achieved through direct molecular interactions with cytoskeletal proteins.
Mitochondria are closely associated with the intermediate filaments (IF) and microtubules networks while muscle creatine kinase (MCK) and glycolytic complexes are tightly associated to the thin filaments. This close relationship explains the seminal observation that remodeling of the cell architecture (cytoskeleton) co-occurs with remodeling of the energy metabolism in diseases such as heart failure or muscle wasting, a remodeling process aggravated by age.

1-Linking integrin signaling, cytoskeleton remodeling and NAD+ homeostasis in the development of dilated cardiomyopathy (DCM) and cardiac aging.

Our objectives are to improve the knowledge on the mechanisms involved in the development of some cardiovascular and skeletal muscle diseases linked to aging. We will notably focus on a project for the team that is the role of the Nrk2 kinase in NAD biosynthesis and NAD homeostasis in cardiac and skeletal muscle aging. We will pursue our research on the SRF-driven gene and microRNA networks in the
context of cardiac aging.

NAD biosynthesis in dilated cardiomyopathy.

We have identified genes involved in the NAD biosynthetic pathway that are differentially regulated in the dilated heart of SRF cardiac mutant and we have characterized a defect in NAD level in this model. NAD is an essential cofactor in the energetic metabolism but it is also a substratum of sirtuins lysin-deacetylases and of poly-ADP-ribosyl polymerases that play a crucial in cell survival, resistance to oxidative stress and gene expression regulation. We will analyze the signaling pathways and pathological consequences of these alterations in the pathogenesis of DCM at the level

Gene and miRNA regulation in the cardiovascular system

SRF has been proposed as an essential regulator of miRNA expression. An array of 659 miRNA in heart has been realized and we have identified 15 miRNA specifically down-regulated in the absence of SRF. A novel regulatory loop among SRF, miR-1 and its targets NCX1 (Ca/Na echanger) and Annexin A5 has been shown. Also, recent data show changes in the transcriptional regulation by polymerase II during cardiac hypertrophy. In this context, we study the function of Bcl11b as a repressor of transcription in cardiomyocytes and stem cells.

Cytoskeletal protein role in cardiac and musculoskeletal remodeling

Desmin KO mice show a cardiomyopathy characterized by calcification, fibrosis and mitochondrial dysfunction, showing the importance of cytoskeletal proteins for muscle tissue integrity. A second model, where SRF inactivation was induced in adult heart show a fast downregulation of muscle creatin kinase affecting actin polymerization
and a desorganization of the desmin network without affecting synemin expression. In synemin KO mice, on the other hand, we observe a singificant reduction in the maximal muscle force and an increase of fatiguability.

2- Implication of IFs in sarcopenic obesity and metabolic disorders.

Our objectives are to better understand the crosstalk between fat and muscle in aging. This project emerges from our new original results showing a crucial role for IFs in the control of fat mass and the fact that, a specialist in muscle wasting, has recently joined our team. The beneficial impact of specific exercises and exercisemimetics to counteract age-induced muscle atrophy.
Several studies show potential SRF implication in cardiac and musculoskeletal aging, as well as in Alzheimer disease (with a role in cerebral vasculature). Our goal is to analyze SRF role during aging in the heart and the vasculature (smooth muscle, endothelium). Also, we have shown that muscle atrophy (cachexia) is associated to myogenic stem cell dysfunction leading to loss of muscle homeostasis. Increased physical activity counteracts cachexia by affecting the levels of circulatory proinflammatory and pro-myogenic factors. The possibility to reproducibly induce the inactivation of SRF and its target genes offers an opportunity to analyze SRF role in the homeostasis of the cardiovascular and musculoskeletal systems at different stages of aging and pathology.
We will focus on two aspects of sarcopenia that are

The impact of physical activity and pharmacological treatments stimulating exercise-induced pathways on sarcopenia and the role of specific transcriptional regulators involved in muscle homeostasis. This topic constitutes a follow up of the previous research of D. Coletti on muscle wasting.The implication of IFs in sarcopenic obesity and metabolic disorder.
The mutation of IF encoding genes is linked to the human pathologies, such as Desmin-related myopathies (DRM) characterized by cytoplasmic desmin aggregates. Nuclear IF lamin A/C mutations are linked to progeria, dilated cardiomyopathy and lipodystrophy. Recently, we have obtained the synemin KO mice. Synemin, an IF protein, is present in the aggregates of DRM patients. Synemin gene encodes three isoforms (180, 150 and 41 kDa) byalternative splicing according to the tissue . Synemin interacts with desmin, α-actinin, vinculin, talin, α -dystrobrevin, utrophin/dystrophin and zyxin, thusintegrating IF and actin cytoskeleton in striated muscle (and ref therein). Ourresults indicate a defect in the organization of the skeletal muscle membraneand muscle regeneration in synemin KO mice, together with dysregulated muscle response to overload. The role of cytoplasmic IFs such as desmin, synemin, vimentin during aging is rarely studied. It has been demonstrated by others and us that vimentin and desmin are targets of AGE (Advanced glycation end-product) Vimentin is increased and modified by oxidative stress in senescent fibroblasts (B. Friguet studies) and desmin increases in the aged striated muscles. Cytoplasmic IFs are linked to the mitochondria dynamics and have an impact on mitochondrial activity.

Collaboration and Implementation

Charles Foix Institute of Longevity (ILCF) (J. Mariani),
Proteomic tools dedicated to oxidized proteins detection (B. Friguet),
Molecular tools and expertise to study NAD biosynthesis pathways (B Brug)
Vascular diseases (P. Lacolley, Inserm Nancy, D. Henrion, Inserm-CNRS Angers),
Cardiac bioenergetics (R. Ventura-Clapier)
ICAN regroups the largest European hospital (Pitié-Salpétrière).
Fat tissue characteristics, B. Fève (ICAN, Saint-Antoine-UPMC). cardiovascular,
musculoskeletal and metabolic diseases.
Heart failure Inserm Châtenay Malabry) and functional cardiac phenotyping (B. Escoubet, Inserm-Bichat Hospital).S. Hatem and J-S. Hulot, Institute of Cardiology-Metabolism-Nutrition (ICAN),. D.Dagelen (Institut Cochin)
European collaborations (G. Tarone, University of Torino, S. Adamo, Sapienza University of Rome, L. de Windt, Netherland
American collaborations (D. Guttridge, hio State University; C. Brenner, Iowa Univ,
Sun and Robson USA)

Laboratory members

Current members 2014:

Zhenlin Li

Directeur de Recherche INSERM, zhenlin.li@upmc.fr

Mathias Mericskay

Chargé de Recherche INSERM, mathias.mericskay@upmc.fr

Zhigang Xue

Chargé de Recherche CNRS, zhigang.xue@upmc.fr

Jean-François Decaux
Chargé de recherche CNRS, jean-francois.decaux@inserm.fr

Jocelyne Blanc

Ingénieur CNRS, Jocelyne.blanc@upmc.fr

Pedro Bausero

Professeur UPMC, Pedro.bausero@upmc.fr

Ara Parlakian

Maître de Conférence UPMC, ara.parlakian@upmc.fr

Dario Coletti

Maître de Conférence UPMC, dario.coletti@snv.jussieu.fr

Jacqueline Gao-Li

Adjointe UPMC, Jacqueline.Gao-Li@snv.jussieu.fr

Barbara Perniconi, Université de Rome Tor Vergata,

Post-Doctorant UPMC, b.perniconi@teletu.it

Denise Paulin

Professeur Emérite, Denise.paulin@upmc.fr

Cynthia Tannous

Doctorante, cynthiajtannous@gmail.com

Alexandra Baccam

Doctorante, alexandraba40@hotmail.com

Aude Angelini

Doctorante

Past Members

Pr Fangyu Wang

Ecole Normale de Hengyang-Chine, wangfy@gmail.com

Dr Christophe Hourdé

Post-Doctorant UPMC, christophehourde@gmail.com

Dr Nicolas Diguet

Post-Doctorant UPMC, nicolas.diguet@snv.jussieu.fr

Youssef Mallat

Doctorant UPMC, mailto:youssef.mallat@hotmail.com

Paola Aulino

Doctorant La Sapiensa (Rome), paola.aulino@yahoo.it

Dr Sheila Martins

Université de Rio de Janeiro-Brésil

sheila@anato.ufrj.br

2009-2011 :Dynamic expression of synemin isoforms in mouse embryonic stem cells and neural derivatives

Dr Guillaume Galmiche

Institut des Cordeliers UPMC-Paris

ggalmiche@free.fr

2007-2010 : SRF in vascular cells

Dr Alexandra Grosfeld

Institut des Cordeliers UPMC-Paris

alexandra.grosfeld@upmc.fr

2007-2008 : MIBP and cardiomyopathies

Eva Tritsch

eva.tritsch@etu.upmc.fr

2011 : An SRF/miR-1 axis regulates NCX1 and Annexin A5 protein levels in the heart andimpacts on cell survival and calcium transients.

Adrien Bernard-Jaoul

jo_f666@yahoo.fr

2009 : Laminin receptor involvement in the anti-angiogenic activity of pigment epithelium-derived factor.

Claudio Areias Franco

Claudio.franco@cancer.org.uk

2008 : Serum response factor is required for sprouting angiogenesis and vascular integrity

Guillaume Gary-Bobo

guillaume.gary-bobo@inserm.fr

2008 : Mosaic inactivation of the serum response factor gene in the myocardium induces focal lesions and heart failure

Luiza Khanamiryan

Luiza Khanamiryan@paris7jussieu.fr

2007 : Self-assembly incompetence of synemin is related to the property of its head and rod domains.

Araksya Izmiryan

araksya.izmiryan@inserm.fr

ALUMNI

2012

Claudia SERRADIFALCO PhD - University of Palermo- Palermo

Catexia and muscles

Eleonora ROSSI Ms - Sapienza University- Roma

Muscle Myosins

Sarah ROUHANA Ms 2 - Université Saint Joseph – Beyrouth

BClIIb transcription inibitor and cardiac hypertrophy

Aikaterini PAPAEFTHYMIOU Ms 2 – Ioanina University - UPMC

BClIIb transcription inhibitor : in skeletal muscle

Angela ARENAS Ms Erasmus – Madrid

Ms: UPMC :Biologie moléculaire et cellulaire - Specialité Génétique

SRF ko mice : and intestinal defects

Violeta COBO Madrid - L3 UPMC

2013

Céline DOUGUET Ms 2- Formation des maîtres – CAPES

Synemin in skeletal muscles

Daniel WINTERrMs1- Université Diderot-P7

Structure, fonction et ingénierie des protéines

Role of SRF in energy metabolism

Alexandra BACCAM Ms2-BMC-UPMC Role of stem cells on cachexia

Tsolere ARAKELIAN Ms1-BMC- UPMC Bcl11 b during cardiac hypertrophy

Cynthia Tannous Ms2-USJ MIBP in cardiomyocytes

2014

Jonathan LEHACAUT Ms2-BIP- UPMC Mir 378 and cardiopathy

Roy El Khoury Ms2-USJ Bcl11 b during cardiac hypertrophy

Publications

2013

Posttranslational modifications of desmin and their implication in biological processes and pathologies.Winter DL, Paulin D, Mericskay M, Li Z.Histochem Cell Biol. 2014 Jan;141(1):1-16.

Proteome Modulation in H9c2 Cardiac Cells by microRNAs miR-378 and miR-378.Mallat Y, Tritsch E, Ladouce R, Winter DL, Friguet B, Li Z, Mericskay M.Mol Cell Proteomics. 2014 Jan;13(1):18-29.

CTIP2 is a negative regulator of P-TEFb.Cherrier T, Le Douce V, Eilebrecht S, Riclet R, Marban C, Dequiedt F, Goumon Y, Paillart JC, Mericskay M, Parlakian A, Bausero P, Abbas W, Herbein G, Kurdistani SK, Grana X, Van Driessche B, Schwartz C, Candolfi E, Benecke AG, Van Lint C, Rohr O.Proc Natl Acad Sci U S A. 2013 Jul 30;110(31):12655-60.

Efficacy of epicardially delivered adipose stroma cell sheets in dilated cardiomyopathy.Hamdi H, Boitard SE, Planat-Benard V, Pouly J, Neamatalla H, Joanne P, Perier MC, Bellamy V, Casteilla L, Li Z, Hagège AA, Mericskay M, Menasché P, Agbulut O.Cardiovasc Res. 2013 Sep 1;99(4):640-7.

SRF selectively controls tip cell invasive behavior in angiogenesis.Franco CA, Blanc J, Parlakian A, Blanco R, Aspalter IM, Kazakova N, Diguet N, Mylonas E, Gao-Li J, Vaahtokari A, Penard-Lacronique V, Fruttiger M, Rosewell I, Mericskay M, Gerhardt H, Li Z.Development. 2013 Jun;140(11):2321-33.

An SRF/miR-1 axis regulates NCX1 and annexin A5 protein levels in the normal and failing heart.Tritsch E, Mallat Y, Lefebvre F, Diguet N, Escoubet B, Blanc J, De Windt LJ, Catalucci D, Vandecasteele G, Li Z, Mericskay M.Cardiovasc Res. 2013 Jun 1;98(3):372-80.

Inactivation of serum response factor contributes to decrease vascular muscular tone and arterial stiffness in mice.Galmiche G, Labat C, Mericskay M, Aissa KA, Blanc J, Retailleau K, Bourhim M, Coletti D, Loufrani L, Gao-Li J, Feil R, Challande P, Henrion D, Decaux JF, Regnault V, Lacolley P, Li Z.Circ Res. 2013 Mar 29;112(7):1035-45

Selective involvement of serum response factor in pressure-induced myogenic tone in resistance arteries.Retailleau K, Toutain B, Galmiche G, Fassot C, Sharif-Naeini R, Kauffenstein G, Mericskay M, Duprat F, Grimaud L, Merot J, Lardeux A, Pizard A, Baudrie V, Jeunemaitre X, Feil R, Göthert JR, Lacolley P, Henrion D, Li Z, Loufrani L.Arterioscler Thromb Vasc Biol. 2013 Feb;33(2):339-46

Substrains of inbred mice differ in their physical activity as a behavior.Coletti D, Berardi E, Aulino P, Rossi E, Moresi V, Li Z, Adamo S.scientificWorldJournal. 2013;2013:237260.

F-κB-mediated Pax7 dysregulation in the muscle microenvironment promotes cancer cachexia.He WA, Berardi E, Cardillo VM, Acharyya S, Aulino P, Thomas-Ahner J, Wang J,Bloomston M, Muscarella P, Nau P, Shah N, Butchbach ME, Ladner K, Adamo S, Rudnicki MA, Keller C, Coletti D, Montanaro F, Guttridge DC.J Clin Invest. 2013 Oct 1.

Static magnetic fields modulate X-ray-induced DNA damage in human glioblastoma primary cells.Teodori L, Giovanetti A, Albertini MC, Rocchi M, Perniconi B, Valente MG, Coletti D.J Radiat Res. 2013 Dec 17

Restoration versus reconstruction: cellular mechanism of skin, nerve and muscle regeneration compared;Coletti D., Teodori L.,LiZ, Beranudin JF., Adamo S., BMC Regen Med Res, in press

NF-κB-mediated Pax7 dysregulation in the musclemicroenvironment promotes cancer cachexia.He WA, Berardi E, Cardillo VM,Acharyya S, Aulino P, Thomas-Ahner J, Wang J, Bloomston M, Muscarella P, Nau P, Shah N, Butchbach ME, Ladner K, Adamo S, Rudnicki MA, Keller C, Coletti D, Montanaro F, Guttridge DC. J Clin Invest. 2013 123(11): 4821–4835.

.2012

Locally expressed IGF1 propeptide improves mouse heart function in induced dilated cardiomyopathy by blocking myocardial fibrosis and SRF-dependent CTGF induction.

Touvron M, Escoubet B, Mericskay M, Angelini A, Lamotte L, Santini MP, Rosenthal N, Daegelen D, Tuil D, Decaux JF. Dis Model Mech. 2012 Jul;5(4):481-91. Epub 2012 Apr 5. PMID:22563064

Smooth muscle cells and vascular diseases.

Michel JB, Li Z, Lacolley P.

Cardiovasc Res. 2012 Jul 15;95(2):135-7. Epub 2012 May 24. No abstract available. PMID:22637748

The vascular smooth muscle cell in arterial pathology: a cell that can take on multiple roles.

Lacolley P, Regnault V, Nicoletti A, Li Z, Michel JB.

Cardiovasc Res. 2012 Jul 15;95(2):194-204. Epub 2012 Mar 31. PMID: 22467316

2011

Muscle creatine kinase deficiency triggers both actin depolymerization and desmin disorganization by advanced glycation end products in dilated cardiomyopathy. Diguet N, Mallat Y, Ladouce R, Clodic G, Prola A, Tritsch E, Blanc J, Larcher JC, Delcayre C, Samuel JL, Friguet B, Bolbach G, Li Z, Mericskay M. J Biol Chem. 2011;286(40):35007-19..

Early growth responsive protein-1 induces desmin null airway smooth muscle hypertrophy through MicroRNA-26a.Mohamed JS, Hajira A, Li Z, Paulin D, Boriek AM.J Biol Chem. 2011 ;286(50):43394-404.

Dynamic expression of synemin isoforms in mouse embryonic stem cells and neural derivatives.de Souza Martins SC, Agbulut O, Diguet N, Larcher JC, Paulsen BS, Rehen SK, Moura-Neto V, Paulin D, Li Z, Xue Z.BMC Cell Biol. 2011;12(1):51

Desmin mutations in the terminal consensus motif prevent synemin-desmin heteropolymer filament assembly.

Chourbagi O, Bruston F, Carinci M, Xue Z, Vicart P, Paulin D, Agbulut O.Exp Cell Res. 2011;317(6):886-97

The pro-myogenic environment provided by whole organ scale acellular scaffolds from skeletal muscle.

Perniconi B, Costa A, Aulino P, Teodori L, Adamo S, Coletti D.

Biomaterials. 2011 Nov;32(31):7870-82.

Characterization of the failing murine heart in a desmin knock-out model using a clinical 3 T MRI scanner".Sprinkart AM, Block W, Träber F, Meyer R, Paulin D, Clemen CS, Schröder R, Gieseke J, Schild H, Thomas D.Int J Cardiovasc Imaging. 2011 Dec 9

2010

Synemin isoforms in astroglial and neuronal cells from human central nervous system.Izmiryan A, Peltekian E, Federici T, Paulin D, Li ZL, Xue ZG. Neurochem Res. 2010;35(6):881-7.

Cardiac conduction disturbances and differential effects on atrial and ventricular electrophysiological properties in desmin deficient mice.Schrickel JW, Stöckigt F, Krzyzak W, Paulin D, Li Z, Lübkemeier I,

Fleischmann B, Sasse P, Linhart M, Lewalter T, Nickenig G, Lickfett L, Schröder R, Clemen CS.J Interv Card Electrophysiol. 2010;28(2):71-80

Synemin interacts with the LIM domain protein zyxin and is essential for cell adhesion and migration.Sun N, Huiatt TW, Paulin D, Li Z, Robson RM.Exp Cell Res. 2010;316(3):491-505.

Structural and dynamic changes of the serum response element and the core domain of serum response factor induced by their association. Stepánek J, Kopecký V Jr, Mezzetti A, Turpin PY, Paulin D, Alpert B, Zentz C. Biochem Biophys Res Commun. 2010;391(1):203-8.

2009

Laminin receptor involvement in the anti-angiogenic activity of pigment epithelium-derived factor. Bernard A, Gao-Li J, Franco CA, Bouceba T, Huet A, Li Z. J Biol Chem. 2009 10480-10490

Multivalent display of quinic acid based ligands for targeting E-selectin expressing cells.Shamay Y, Paulin D, Ashkenasy G, David A.J Med Chem. 2009;52(19):5906-15.

E-selectin binding peptide-polymer-drug conjugates and their selective cytotoxicity against vascular endothelial cells.Shamay Y, Paulin D, Ashkenasy G, David A.Biomaterials. 2009 6460-6468

2008

Myofiber integrity depends on desmin network targeting to Z-disks and costameres via distinct plectin isoformsPatryk Konieczny, Peter Fuchs, Siegfried Reipert, Wolfram S. Kunz, Anikó Zeöld, Irmgard Fischer, Denise Paulin, Rolf Schröder, Gerhard Wiche

J Cell Biol. 2008; 181(4): 667–681. doi: 10.1083/jcb.20071105

Synemin isoforms during mouse development: multiplicity of partners in vascular and neuronal systems. Izmiryan A, Franco CA, Paulin D, Li Z, Xue Z. Exp Cell Res. 2009;315(5):769-83

Serum response factor is required for sprouting angiogenesis and vascular integrity. Franco CA, Mericskay M, Parlakian A, Gary-Bobo G, Gao-Li J, Paulin D, Gustafsson E, Li Z. Dev Cell. 2008;15(3):448-61.

Self-assembly incompetence of synemin is related to the property of its head and rod domains.Khanamiryan L, Li Z, Paulin D, Xue Z. Biochemistry. 2008;47(36):9531-

Mosaic inactivation of the serum response factor gene in the myocardium induces focal lesions and heart failure. Gary-Bobo G, Parlakian A, Escoubet B, Franco CA, Clément S, Bruneval P, Tuil D, Daegelen D, Paulin D, Li Z, Mericskay M. Eur J Heart Fail. 2008;10(7):635-45

Role of desmin in active force transmission and maintenance of structure during growth of urinary bladder.Scott RS, Li Z, Paulin D, Uvelius B, Small JV, Arner A.Am J Physiol Cell Physiol. 2008;295(2):C324-31.

Identification of a repeated domain within mammalian alpha-synemin that interacts directly with talin.Sun N, Critchley DR, Paulin D, Li Z, Robson RM.Exp Cell Res. 2008;314(8):1839-49.

Human alpha-synemin interacts directly with vinculin and metavinculin.Sun N, Critchley DR, Paulin D, Li Z, Robson RM.Biochem J. 2008;409(3):657-67.

2007

Intermediate filament-like protein syncoilin in normal and myopathic striated muscle.McCullagh KJ, Edwards B, Poon E, Lovering RM, Paulin D, Davies KE.Neuromuscul Disord. 2007;17(11-12):970-9

Inducible mouse model of chronic intestinal pseudo-obstruction by smooth muscle-specific inactivation of the SRF gene. Mericskay M, Blanc J, Tritsch E, Moriez R, Aubert P, Neunlist M, Feil R, Li Z. Gastroenterology. 2007;133(6):1960-70

Delayed liver regeneration in mice lacking liver serum response factor. Latasa MU, Couton D, Charvet C, Lafanechère A, Guidotti JE, Li Z, Tuil D, Daegelen D, Mitchell C, Gilgenkrantz H. Am J Physiol Gastrointest Liver Physiol. 2007;292(4):G996-G1001.

Role of alpha1beta1-integrin in arterial stiffness and angiotensin-induced arterial wall hypertrophy in mice.Louis H, Kakou A, Regnault V, Labat C, Bressenot A, Gao-Li J, Gardner H, Thornton SN, Challande P, Li Z, Lacolley P.Am J Physiol Heart Circ Physiol. 2007 Oct;293(4):H2597-604.

2006

New role for serum response factor in postnatal skeletal muscle growth and regeneration via the interleukin 4 and insulin-like growth factor 1 pathways. Charvet C, Houbron C, Parlakian A, Giordani J, Lahoute C, Bertrand A, Sotiropoulos A, Renou L, Schmitt A, Melki J, Li Z, Daegelen D, Tuil D. Mol Cell Biol. 2006

Conditional inactivation of the murine serum response factor in the pancreas leads to severe pancreatitis. Miralles F, Hebrard S, Lamotte L, Durel B, Gilgenkrantz H, Li Z, Daegelen D, Tuil D, Joshi RL. Lab Invest. 2006;86(10):1020-36.

Different expression of synemin isoforms in glia and neurons during nervous system development. Izmiryan A, Cheraud Y, Khanamiryan L, Leterrier JF, Federici T, Peltekian E, Moura-Neto V, Paulin D, Li Z, Xue ZG. Glia. 2006;54(3):204-13.

C-->G base mutations in the CArG box of c-fos serum response element alter its bending flexibility. Consequences for core-SRF recognition.Stepanek J, Vincent M, Turpin PY, Paulin D, Fermandjian S, Alpert B, Zentz C.FEBS J. 2007;274(9):2333-48.

New insights into the molecular basis of desmoplakin- and desmin-related cardiomyopathies.Lapouge K, Fontao L, Champliaud MF, Jaunin F, Frias MA, Favre B, Paulin D, Green KJ, Borradori L.J Cell Sci. 2006;119(Pt 23):4974-85.

Hepatic stellate cells express synemin, a protein bridging intermediate filaments to focal adhesions Uyama N, Zhao L, Van Rossen E, Hirako Y, Reynaert H, Adams DH, Xue Z, Li Z, Robson R, Pekny M, Geerts A. Gut. 2006 Sep;55(9):1276-89. Epub 2006 Feb 16

Reviews and books

[Intermediate filament associated diseases].

Paulin D, Diguet N, Xue Z, Li Z. Biol Aujourdhui. 2011;205(3):139-46. Review

Intermediate Filament Expression in Mouse Embryonic Stem Cells and Early Embryos.

Xue ZG, Mounra-Neto V, Izmiryan A, de Souza Martins SC, Larcher JC, Paulin D, Li Z: In Perspectives of Stem Cells: From Tools for Studying Mechanisms of Neuronal Differentiation towards Therapy. Edited by:Ulrich H. Springer Science; 2010:59-72. Review.

SRF in angiogenesis: branching the vascular system.

Franco CA, Li Z. Cell Adh Migr. 2009 Jul-Sep;3(3):264-7. Review.

Vimentin during development: expression, regulation and functions

Li Zhenlin, Duprey Philippe, Izmyrian Araksya, Parlakian Ara, Blanc Jocelyne, Xue Zhigang and Paulin Denise, Nova publisher. 2012. Review

Thèses

Mallat Youssef ; La régulation du cytosquelette et du métabolisme énergétique par miR-378 et 378* dans les cardiomyocytes : 17 septembre 2013- UPMC- Paris 6
Proteome Modulation in H9c2 Cardiac Cells by microRNAs miR-378 and miR-378. Mallat Y, Tritsch E, Ladouce R, Winter DL, Friguet B, Li Z, Mericskay M.Mol Cell Proteomics. 2014 Jan;13(1):18-29.
An SRF/miR-1 axis regulates NCX1 and annexin A5 protein levels in the normal and failing heart.Tritsch E, Mallat Y, Lefebvre F, Diguet N, Escoubet B, Blanc J, De Windt LJ, Catalucci D, Vandecasteele G, Li Z, Mericskay M.Cardiovasc Res. 2013 Jun 1;98(3):372-80.

Diguet Nicolas ; Couplage de l’expression des gènes du cytosquelette et du métabolisme énergétique par SRF : implications dans la cardiomyopathie dilatée ; 21 septembre 2011 – UPMC- Paris 6

Biol Chem. 2011;286(40):35007-19..

BMC Cell Biol. 2011;12(1):51

[Intermediate filament associated diseases].

Paulin D, Diguet N, Xue Z, Li Z. Biol Aujourdhui. 2011;205(3):139-46. Review

Tritsch Eva ; Rôle de SRF dans l’expression des miRNA et des proteins cardiaques impliqués dans l’apoptose et les flux calciques ; 30 septembre 2011 – UPMC Paris6

Inducible mouse model of chronic intestinal pseudo-obstruction by smooth muscle-specific inactivation of the SRF gene. Mericskay M, Blanc J, Tritsch E, Moriez R, Aubert P, Neunlist M, Feil R, Li Z.

Gastroenterology. 2007;133(6):1960-70

An SRF/miR-1 axis regulates NCX1 and Annexin A5 protein levels in the heart and impacts on cell survival and calcium transients.

Eva Tritsch, Youssef Mallat, Florence Lefebvre, Nicolas Diguet, Brigitte Escoubet,Jocelyne Blanc, Veronique Baudrie, Jean-Luc Elghozi, Leon De Windt, Daniele Catalucci, GrégoireVandecasteele, Zhenlin Li, Mathias Mericskay, soumis

Bernard-Jaoul Adrien ; Identification et caractérisation de l’interaction du PEDF (Pigmented epithelium derived factor) avec le récepteur de la laminine 37LRP/67LR.- 2009 UPMC – Paris6

Laminin receptor involvement in the anti-angiogenic activity of pigment epithelium-derived factor. Bernard A, Gao-Li J, Franco CA, Bouceba T, Huet A, Li Z.

J Biol Chem. 2009 10480-10490

Areias Franco Franco ; Rôle du facteur SRFdans les cellules endothéliales ;30 septembre 2008 - Université Diderot paris7

Serum response factor is required for sprouting angiogenesis and vascular integrity. Franco CA, Mericskay M, Parlakian A, Gary-Bobo G, Gao-Li J, Paulin D, Gustafsson E, Li Z.

Dev Cell. 2008;15(3):448-61.

Synemin isoforms during mouse development: multiplicity of partners in vascular and neuronal systems. Izmiryan A, Franco CA, Paulin D, Li Z, Xue Z.

Exp Cell Res. 2009;315(5):769-83

SRF in angiogenesis: branching the vascular system. Franco CA and Li Z.

Cell Adh Migr. 2009 Jul-Sep;3(3):264-7. Review.

Gary-Bobo Guillaume ; Rôle du Facteur de Réponse au Sérum dans le remodelage cardiaque post natal chez la souris- ; 2 juillet 2008 – Université Diderot Paris 7

Eur J Heart Fail. 2008;10(7):635-45

Serum response factor is required for sprouting angiogenesis and vascular integrity. Franco CA, Mericskay M, Parlakian A, Gary-Bobo G, Gao-Li J, Paulin D, Gustafsson E, Li Z.

Dev Cell. 2008;15(3):448-61.

Izmiryan Araksya : Expression des synémines chez la souris au cours du développement embryonnaire ; 28 mars 2007- Université Diderot Paris-7

Synemin isoforms in astroglial and neuronal cells from human central nervous system.Izmiryan A, Peltekian E, Federici T, Paulin D, Li ZL, Xue ZG. Neurochem Res. 2010;35(6):881-7.

Synemin isoforms during mouse development: multiplicity of partners in vascular and neuronal systems. Izmiryan A, Franco CA, Paulin D, Li Z, Xue Z. Exp Cell Res. 2009;315(5):769-83

Intermediate Filament Expression in Mouse Embryonic Stem Cells and Early Embryos.

Vimentin during development: expression, regulation and functions

Li Zhenlin, Duprey Philippe, Izmyrian Araksya, Parlakian Ara, Blanc Jocelyne, Xue Zhigang and Paulin Denise, Nova publisher. Review

SRF

dimanche 13 juillet 2014

POSTDOC POSITION IN SKELETAL MUSCLE PHYSIO-PATHOLOGY

jeudi 27 mars 2014

vendredi 24 février 2012

Research interests