 Fuxin Shi, PH.D., B.M.
| Title | Instructor in Otology and Laryngology |
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| Institution | Massachusetts Eye and Ear Infirmary |
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| Department | Otology and Laryngology |
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| Address | Massachusetts Eye & Ear Infrm
Eaton Peabody Laboratory
243 Charles St
Boston MA 02114
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| Phone | 617/573-3745 |
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 Overview The objective of our research is to investigate molecular pathways in hair cell development, and to exploit these pathways in order to regenerate sensory hair cells and restore hearing. We aim to also explore novel methods for the prevention of hair cell loss during ototoxic insult and acoustic trauma.
Wnt/beta-catenin signaling is a well-known pathway essential for stem cell maintenance and differentiation. In the ear, we found that Wnt signaling controls the expression of Atoh1, which is a key gene in hair cell development. In a recent study, we identified one downstream target of Wnt signaling to be a marker of inner ear stem cells. The Wnt pathway controls the fate of those stem cells during neonatal development. Specifically, in the developing embryo, Wnt signaling is active in inner ear stem cells at the time that hair cell differentiation is taking place, but disappears in the mature inner ear despite the persistence of inner ear stem cells. These findings suggest that the lack of regenerative ability in the inner ear can be attributed, at least in part, to the loss of Wnt signaling. Based on our studies, we will develop novel strategies to re-activate Wnt signaling in inner ear stem cells in order to regenerate hair cells.
Bibliographic
Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications.
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Shi F, Edge AS. Prospects for replacement of auditory neurons by stem cells. Hear Res. 2013 Mar; 297:106-12.
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Shi F, Kempfle JS, Edge AS. Wnt-responsive Lgr5-expressing stem cells are hair cell progenitors in the cochlea. J Neurosci. 2012 Jul 11; 32(28):9639-48.
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Shi F, Cheng YF, Wang XL, Edge AS. Beta-catenin up-regulates Atoh1 expression in neural progenitor cells by interaction with an Atoh1 3' enhancer. J Biol Chem. 2010 Jan 1; 285(1):392-400.
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Shi F, Corrales CE, Liberman MC, Edge AS. BMP4 induction of sensory neurons from human embryonic stem cells and reinnervation of sensory epithelium. Eur J Neurosci. 2007 Dec; 26(11):3016-23.
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Hoekstra D, Rejman J, Wasungu L, Shi F, Zuhorn I. Gene delivery by cationic lipids: in and out of an endosome. Biochem Soc Trans. 2007 Feb; 35(Pt 1):68-71.
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Shi F, Gounko NV, Wang X, Ronken E, Hoekstra D. In situ entry of oligonucleotides into brain cells can occur through a nucleic acid channel. Oligonucleotides. 2007; 17(1):122-33.
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Wang X, Shi F, Wösten HA, Hektor H, Poolman B, Robillard GT. The SC3 hydrophobin self-assembles into a membrane with distinct mass transfer properties. Biophys J. 2005 May; 88(5):3434-43.
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Shi F, Hoekstra D. Effective intracellular delivery of oligonucleotides in order to make sense of antisense. J Control Release. 2004 Jun 18; 97(2):189-209.
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Swinny JD, Kalicharan D, Brouwer N, Biber K, Shi F, Gramsbergen A, van der Want JJ. The postnatal developmental expression pattern of urocortin in the rat olivocerebellar system. J Comp Neurol. 2004 Apr 19; 472(1):40-51.
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Shi F, Visser WH, de Jong NM, Liem RS, Ronken E, Hoekstra D. Antisense oligonucleotides reach mRNA targets via the RNA matrix: downregulation of the 5-HT1A receptor. Exp Cell Res. 2003 Dec 10; 291(2):313-25.
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Shi F, Wasungu L, Nomden A, Stuart MC, Polushkin E, Engberts JB, Hoekstra D. Interference of poly(ethylene glycol)-lipid analogues with cationic-lipid-mediated delivery of oligonucleotides; role of lipid exchangeability and non-lamellar transitions. Biochem J. 2002 Aug 15; 366(Pt 1):333-41.
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Shi F, Nomden A, Oberle V, Engberts JB, Hoekstra D. Efficient cationic lipid-mediated delivery of antisense oligonucleotides into eukaryotic cells: down-regulation of the corticotropin-releasing factor receptor. Nucleic Acids Res. 2001 May 15; 29(10):2079-87.
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