Position:

Professor of Neuroscience and Research Director

Academic and scientific tracks:

Zine started his scientific career in 1991 at the laboratory of hearing developmental neuobiology at the university of Clermont-Ferrand, France. In 1994, he defended his Ph.D. thesis. Then, he moved as a post-doctoral researcher, first to Prof. L. Schweitzer’s lab at the university of Kentucky, where he studied various patterns of cochlear development and as associate researcher at the University of Lausanne with Prof. F. de Ribaupierre to work on cellular and molecular mechanisms of hair cell differentiation and regeneration. In 2002, he was appointed as Associate Professor at the university of Montpellier where he teaches sensory biophysics to pharmaceutical and medical students. He also gives lectures at advanced graduate programs in auditory neurosciences and sensory stem cell biology. Since his appointment, he carried out research activities devoted to inner ear development protection and regeneration at the INSERM 583 in Montpellier until 2011. Then, he has integrated as a researcher-associate the CNRS 7260 in Marseille, where he headed a research group working on the European FP7-Health Innovation project « Otostem ». Since, 2018, he joined the Laboratory Bioengineering and Nanosciences at the university of Montpellier to continue his research on stem cell biology and neurosensory regeneration.

Main achievements in 4 areas:
– HC differentiation: understanding the role of Notch/Hes signaling pathway in the development of the cochlear hair cells (JNeurosci, Development...).
– HC protection: interfering with JNK pathway with small peptides: the first demonstration of the role of  the JNK inhibitor (D-JNK-1) as an otoprotective peptide against aminoglycosides ototoxicity and acoustic trauma induced hearing loss (JNeurosci, Current Signal Transduction Therapy…).
– Sensory stem cell biology: first isolation and characterization of adult stem cells from the mammalian cochlea by a side population analysis (Stem cells, Mechanisms of Development...).
– HC regeneration: in vitro induction and in vivo engraftment of human otic progenitors derived from pluripotent stem cells in the damaged cochlea (PlosOne, Fnmol, Molecular Therapy…)

Current research in the Zine Lab falls into 3 main areas:

 

  • Human stem-cell based models for understanding mechanisms of development

 

  • Human stem-cell engineering and cell therapy for hearing loss

 

    • Spiral ganglion neuron regeneration

 

  • Journal covers:

  • Funded by (past and present):

 

 


Current Position

Professor of Neuroscience (full-time tenured faculty), Montpellier University, France

Research Director, Laboratory of Engineering and Biosciences, Montpellier University, France

Education and Degree

1990 Master in Cellular Physiology, Blaise Pascal University, Clermont-FD, France

1994 Ph.D. in Neuroscience (Highest honor), Blaise Pascal University, Clermont-FD, France

2002 HDR in Neuroscience (Highest honor), Auvergne University, Clermont-FD, France

Past Positions

1994-1996 Research Associate, Department of Neurobiology, University of Kentucky, USA

1996-2001 Research associate, Institute of Physiology, University of Lausanne, Switzerland

2006 Visiting Scientist, Riken Brain Science Institute, Tokyo, Japan

2008 Visiting Professor, Stanford University, Stanford, USA

2011 Visiting Scientist, Sao Paulo University, Sao Paulo, Brazil

2002-2010 PI Institute of Neuroscience, INSERM UMR 583

2011-2017 PI Integrative and Adaptive Neurosciences, CNRS UMR 7260

Awards

2006 RIKEN Brain Science Institute fellowship

2006 Japan Society for the Promotion of Science Fellowship

2011 Sao Paulo University Travel Award

Research Funding

Fondation de France (2005-2009)

Stanford-France Interdisciplinary Studies (2010-2012)

French National Research Agency – ANR (2010-2014)

FP7-HEALTH-2013-INNOVATION-1 (2013-2017), Otostem consortium

Professional memberships

1996-present: Association for Research in Otolaryngology

2010-present: International Society for Stem Cell Research

2015-present: French Society for Gene and Cell Therapy

2016-present: French Society for Stem Cell Research

Editorial Board

2004-present: Recent Patents on CNS Drug Discovery

2008-present: Acta Otolaryngology  

2010-present: Senior Member (Neuroscience section) of Facultyof1000

2019: Associate Editor Frontiers in Cell/Developmental Biology

Mentoring

Supervising several graduate and undergraduate students on multidisciplinary topics (Neurosciences, Developmental Neurobiology, Stem Cells, Cell based Therapy Regenerative medicine) in different laboratories in USA, Switzeland and France.

– Stem cells, Biomaterials, Regeneration

– Adult stem cells, Pluripotent stem cells, Organoids

– Otic sensory progenitors

– Modeling human inner ear differentiation with pluripotent stem cells

– Human stem cell engineering for hearing loss

– Lopez, A, Lahlou, H, Cazals, Y, Brezun, JM, Ripoll, C, Quan, W, Edge, A, Zine, A (2019). Engraftment of human stem cell-derived otic progenitors in the damaged cochlea. Molecular Therapy, https://doi.org/10.1016/j.ymthe.2019.03.018. PMID: 31005598.

– Lahlou H, Nivet E, Lopez A, Fontbonne A, Assou S, Zine A (2018). Enrichment and characterization of human otic sensory progenitors derived from induced pluripotent stem cells. Front. Mol. Neurosci.11:452.

– Lahlou, H, Lopez, A, Fontbonne, A, Nivet, E, Zine, A (2018). Modeling human early otic sensory cell development with induced pluripotent stem cells. PLoS ONE 13(6): e0198954.

– Abboud N, Fontbonne A, Watabe, I, Tonetto A, Brezun, JM, Feron F, Zine A (2017). Culture conditions impact the maturation of traceable, transplantable mouse embryonic stem cell-derived otic progenitor cells. J Tissue Eng Regen Med.11(9):2629-2642.

– Dinh C, Goncalves S, Bas E, Van De Water T, Zine A (2015). Molecular regulation of auditory hair cell death and approaches to protect sensory receptor cells and/or stimulate repair following acoustic trauma. Front Cell Neurosci. 9:96.

– Zine A (2014). 3D revolution of stem cells: Generation of ear sensory epithelia in vitro. Med Sci, 30: 952 954.

– Zine A, Lowenheim H, Fritzsch B (2014). Toward translating molecular ear development to generate hair cells from stem cells. In: Kursad T, eds. Adult stem cells. Springer, 2014: 111-161.

– Smeti I, Watabe I, Savary E, Fontbonne A, Zine A (2014). HMGA2, the architectural transcription factor high mobility group, is expressed in the developing and mature mouse cochlea. PLoS One, 9(2): e88757.

– Smeti I, Assou S, Savary E, Masmoudi S, Zine A (2012). Transcriptomic analysis of the developing and adult mouse cochlear sensory epithelia. PLoS One, 7(8): e42987.

– Smeti I, Savary E, Capelle V, Hugnot JP, Uziel A, Zine, A (2011). Expression of candidate markers for stem/progenitor cells in the inner ears of developing and adult GFAP and nestin promoter- GFP transgenic mice. Gene Expression Patterns,11:22-32.

– Jonkamonwiwat N, Zine A, Rivolta MN (2010). Stem cell based therapy in the inner ear: appropriate donor cell types and routes for transplantation. Curr Drug Targets, 11:888-897.

– Abi-Hachem R, Zine A, Van De Water T (2010). The Injured cochlea as a target for inflammatory processes, initiation of cell death pathways and application of related otoprotectives strategies. Recent Patents CNS Drug Discov, 5:147-163.

– Katayama K, Zine, Fritzsch B, Aruga J (2009). Disorganized innervation and neuronal loss in the inner ear of Slitrk6-deficient mice. PLoS One, 4(11): e7786.

– Sabourin J, Ackema K, Ohayon D, Guichet P, Perrin F, Garces A, Ripoll C, Charité J, Simonneau L, Kettenmann H, Zine A, Privat A, Valmier J, Pattyn A, Hugnot J (2009). A mesenchymal-likeZeb1(+) niche harbors dorsal radial GFAP(+) stem cells in the spinal cord. Stem Cells, 11:2722-33.

– Savary E, Santo J, Hugnot JP, Chabbert C, Uziel A, Zine A (2008). Cochlear stem progenitor cellsfrom a postnatal cochlea respond to Jagged1 and demonstrate that Notch signaling promotes sphere formation and sensory potential. Mechanisms of Development,125:674-686.

– Savary E, Hugnot JP, Chassigneux Y, Travo C, Duperray C, Van De Water T, Zine A (2007). Distinct population of cochlear stem/progenitor cells can be isolated from the postnatal mouse  cochlea using side population analysis. Stem Cells, 25:332-339.

– Zine A, Uziel A, Beckmann J, Bonny C (2007). Blocking apoptotic intracellular signaling cascades with cell-permeable peptides. Current Signal Transduction Therapy, 2:175-179.


 2019- Lopez, A, Lahlou, H, Cazals,Y, Chabbert, C Wang, Q, Edge, A. Zine, A. Human otic progenitors derived from pluripotent stem cells engraft and differentiate  in auditory epithelium of animal model of ototoxicity. Association for Research in Otolaryngology(ARO), Baltimore, USA.

2018– Lahlou H Lopez A, Cazals Y, Zine, A. Migration, integration and differentiation of human induced pluripotent stem cell-derived otic progenitors following transplantation in animal model of sensorineural hearing loss. 11th conference on Stem Cell and Regenerative Medicine, Helsenki, Finland.

2017– Zine A, Lahlou H, Lopez A, Cazals Y. Human Induced Pluripotent Stem-Cell-derived Otic Progenitors for Inner Ear Cell-based Therapy. BIT’s 11th World Congress of Regenerative Medicine and Stem Cell. Singapore.

2017– Lopez A, Lahlou H, Brezun JM, Cazals Y, Zine, A. Derivation of otic sensory progenitorsfrom human induced pluripotent stem cells and in vivo approaches for transplantation into the cochlea of a guinea pig model of ototoxicity. International Symposium on Inner Ear Therapies, Marrackech, Morocco.

2017– Lopez A, Lahlou H, Cazals Y, Zine A. Future perspectives in developing stem cell-based therapy for hearing loss. Euroclone 3rd International Workshop: Isolation Techniques in Advanced Therapy Applications. Lausanne, Switzerland.

2017– Lopez A, Lahlou H, Fontbonne A, Brezun JM, Cazals Y, Zine A. Fate of human induced pluripotent stem cell-derived otic progenitors transplanted into the cochlea of a guinea pig model of ototoxic drug-induced hair cell death and hearing loss. Association for Research in Otolaryngology (ARO), Baltimore, USA.

 

2016– Lahlou H, Lopez A, Fontbonne A, Feron F, Nivet E, Zine A. Modeling of early human otic sensory lineage with induced pluripotent stem cells. EMBO 2016 Symposium, Organoids: Modelling Organ Development and Disease in 3D Culture. Heidelberg, Germany.

2016– Lahlou H, Lopez A, Fontbonne A, Feron F, Nivet E, Zine A. Notch modulation impacts the differentiation of human induced pluripotent stem cell-derived otic progenitor cells. Workshop on Inner Ear Biology. Montpellier.

2016– Lopez A, Lahlou H, Fontbonne A, Brezun JM, Cazals Y, Zine A. Establishment of a cell therapy model for hearing loss: From in vitro human otic progenitors to their in vivo fate after engraftment in guinea pig cochlea. Workshop on Inner Ear Biology. Montpellier.

2016– Lahlou, H, Lopez, A, Fontbonne, A, Feron, F, Nivet, E, Zine, A. Differentiation of human induced pluripotent stem cell-derived posterior otic placode progenitors into inner earhair cell lineage, Association for Research in Otolaryngology (ARO), San Diego, USA.

2016– Lahlou, H, Lopez, A, Fontbonne, A, Feron, F, Nivet, E, Zine, A. Differentiation of human induced pluripotent stem cell-derived otic placode progenitors into inner ear hair cell lineage. French Society for Gene and Cell Therapy Annual Conference. Marseille.

2014– Abboud N, Fontbonne A, Brezun JM, Feron F, Zine A. In vitro transition of mouse embryonic stem-cell differentiation into inner ear progenitors. Workshop on Inner Ear Biology. Kyoto, Japan.

2014– Lahlou H, Fontbonne A, Brezun JM, Chabbert C, Feron F, Zine, A. Controlled differentiation of human induced pluripotent stem cells into an otic progenitor cell fate. Workshop onInner Ear Biology. Sheffield, UK.

2014– Zine A, Fontbonne A, Smeti I, Watabe I, Abboud N, Feron F. RNA microarray analysis in mouse cochlea reveals Hmga2, the high mobility group transcription factor, in the developing and mature inner ear sensory epithelia. Association for Research inOtolaryngology (ARO), San Diego, USA.

2013– Abboud N, Fontbonne A, Watabe I, Feron F, Zine A. Directed differentiation of inner ear hair cell progenitors from mouse embryonic stem cells. International Society for Stem Cell Research: Stem Cells in Translation. Florence, Italy.

2013– Abboud N, Watabe I, Feron F, Zine A. Différenciation des cellules souches embryonnaires en progéniteurs des cellules ciliées de l’oreille interne. 2ème Congrès: autour de la cellule  souche, Bordeaux, France.

Mail : azel.zine@umontpellier.fr

Otostem

Researchgate