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    Fen-Biao Gao PhD

    TitleProfessor
    InstitutionUniversity of Massachusetts Medical School
    DepartmentNeurology
    AddressUniversity of Massachusetts Medical School
    368 Plantation Street, Room AS6-1051
    Worcester MA 01605
    Phone508-856-8504
      Other Positions
      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentCell Biology

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentInterdisciplinary Graduate Program

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentMD/PhD Program

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentNeuroscience

      InstitutionUMMS - Programs, Centers and Institutes
      DepartmentRNA Therapeutics Institute

        Overview 
        Narrative

        Positions

        • 09.1990–09.1995    PhD Student, Duke University Medical Center
        • 10.1995–09.1997    Postdoctoral Fellow, University College London
        • 10.1997–06.2000    Postdoctoral Fellow, University of California, San Francisco (UCSF)
        • 07.2000–05.2006    Assistant Investigator/Assistant Professor, Gladstone/UCSF
        • 06.2006–01.2010    Associate Investigator/Associate Professor, Gladstone/UCSF
        • 02.2010–present     Professor, Department of Neurology, UMMS

        Honors and Awards

        • 1995                Departmental Norman Conant Award, Duke University
        • 1995–1998      Hitchings-Elion Fellowship, Burroughs Wellcome Fund
        • 1998–2000      Senior Postdoctoral Fellowship, American Cancer Society California Chapter
        • 2001                Sloan Research Fellow in Neuroscience, Alfred P. Sloan Foundation
        • 2002                Klingenstein Fellow in Neuroscience, Esther A. and Joseph Klingenstein Fund
        • 2002                McKnight Neuroscience of Brain Disorders Award, McKnight Foundation
        • 2014                Fellow, American Neurological Association

         

        Research Focus: Understanding Frontotemporal Dementia and Neuronal microRNAs

        Dr. Fen-Biao Gao

        Frontotemporal dementia(FTD) is an age-dependent neurodegenerative condition associated with focalatrophy of the frontal and/or temporal lobes and recognized now as the mostcommon form of dementia before the age of 60. Unfortunately, the molecularpathogenesis of FTD remains largely unknown and effective treatments are notavailable. Recent exciting advances indicate that FTD is often associated withamyotrophic lateral sclerosis (ALS) and several genes are involved in thepathogenesis of both FTD and ALS, including CHMP2B, TDP-43, FUS, and C9ORF72.How these mutant proteins cause or contribute to neuronal dysfunction and neurodegenerationin FTD remains poorly defined.

        A few years ago, we cloned anovel Drosophila gene called shrub, which encodes a key componentof ESCRT-III and regulates dendritic morphogenesis. In cultured corticalneurons, we found that dysfunctional ESCRT-III, lacking essential components(such as mSnf7-2, one of the mouse homologs of Shrub) or containing ectopicallyexpressed FTD3-associated mutant CHMP2B, causes dendritic retraction,autophagosome accumulation and eventual neurodegeneration. Through an unbiasedgenetic screen in a Drosophila modelof FTD3, we identified several genetic modifiers of CHMP2B toxicity in vivothat are currently being characterized. We have also been using Drosophila models to study other FTD genes.

        We have also established patient-specific inducedpluripotent stem cells (iPSC) models of FTD with mutations in progranulin, C9ORF72and other genes. Over the next a few years, we will use a combination ofmolecular, cellular, and genetic approaches in both Drosophila and iPSCs models to further dissect the pathogenicmechanisms involving these FTD disease genes. Our ultimate goal is to identifycommon underlying pathogenic pathways as potential targets for therapeuticinterventions. 

        Another research interest in our laboratoryis the microRNA pathway. The roles of this pathway in FTD-associated neurodegeneration will beinvestigated in detail.

         

         



        Rotation Projects

        Project 1: Establish and characterize novel fly models of frontotemporal dementia and related neurodegenerative disorders.

        Project 2: Investigate the roles of the microRNA pathway in neurodegeneration in fly and mammalian model systems.



        Post Docs

        A postdoctoral position is available to study frontotemporal dementia and related neurodegenerative diseases in human iPSC models or Drosophila models. Candidates with strong training backgrounds in molecular and cellular biology are encouraged to apply.  (Updated on March 1, 2014)



        Bibliographic 
        selected publications
        List All   |   Timeline
        1. Gascon E, Gao FB. The Emerging Roles of MicroRNAs in the Pathogenesis of Frontotemporal Dementia-Amyotrophic Lateral Sclerosis (FTD-ALS) Spectrum Disorders. J Neurogenet. 2014 Feb 10.
          View in: PubMed
        2. Lee WC, Almeida S, Prudencio M, Caulfield TR, Zhang YJ, Tay WM, Bauer PO, Chew J, Sasaguri H, Jansen-West KR, Gendron TF, Stetler CT, Finch N, Mackenzie IR, Rademakers R, Gao FB, Petrucelli L. Targeted manipulation of the sortilin-progranulin axis rescues progranulin haploinsufficiency. Hum Mol Genet. 2014 Mar 15; 23(6):1467-78.
          View in: PubMed
        3. Cheruiyot A, Lee JA, Gao FB, Ahmad ST. Expression of mutant CHMP2B, an ESCRT-III component involved in frontotemporal dementia, causes eye deformities due to Notch misregulation in Drosophila. FASEB J. 2014 Feb; 28(2):667-75.
          View in: PubMed
        4. Zhang Z, Almeida S, Lu Y, Nishimura AL, Peng L, Sun D, Wu B, Karydas AM, Tartaglia MC, Fong JC, Miller BL, Farese RV, Moore MJ, Shaw CE, Gao FB. Downregulation of microRNA-9 in iPSC-derived neurons of FTD/ALS patients with TDP-43 mutations. PLoS One. 2013; 8(10):e76055.
          View in: PubMed
        5. Lu Y, Zhang Z, Sun D, Sweeney ST, Gao FB. Syntaxin 13, a Genetic Modifier of Mutant CHMP2B in Frontotemporal Dementia, Is Required for Autophagosome Maturation. Mol Cell. 2013 Oct 1.
          View in: PubMed
        6. Almeida S, Gascon E, Tran H, Chou HJ, Gendron TF, Degroot S, Tapper AR, Sellier C, Charlet-Berguerand N, Karydas A, Seeley WW, Boxer AL, Petrucelli L, Miller BL, Gao FB. Modeling key pathological features of frontotemporal dementia with C9ORF72 repeat expansion in iPSC-derived human neurons. Acta Neuropathol. 2013 Jul 9.
          View in: PubMed
        7. Filiano AJ, Martens LH, Young AH, Warmus BA, Zhou P, Diaz-Ramirez G, Jiao J, Zhang Z, Huang EJ, Gao FB, Farese RV, Roberson ED. Dissociation of Frontotemporal Dementia-Related Deficits and Neuroinflammation in Progranulin Haploinsufficient Mice. J Neurosci. 2013 Mar 20; 33(12):5352-5361.
          View in: PubMed
        8. Almeida S, Zhang Z, Coppola G, Mao W, Futai K, Karydas A, Geschwind MD, Tartaglia MC, Gao F, Gianni D, Sena-Esteves M, Geschwind DH, Miller BL, Farese RV, Gao FB. Induced Pluripotent Stem Cell Models of Progranulin-Deficient Frontotemporal Dementia Uncover Specific Reversible Neuronal Defects. Cell Rep. 2012 Oct 9.
          View in: PubMed
        9. Li Z, Lu Y, Xu XL, Gao FB. The FTD/ALS associated RNA binding protein TDP-43 regulates the robustness of neuronal specification through microRNA-9a in Drosophila. Hum Mol Genet. 2012 Oct 5.
          View in: PubMed
        10. González-Pérez P, Lu Y, Chian RJ, Sapp PC, Tanzi RE, Bertram L, McKenna-Yasek D, Gao FB, Brown RH. Association of UBQLN1 mutation with Brown-Vialetto-Van Laere syndrome but not typical ALS. Neurobiol Dis. 2012 Jul 2.
          View in: PubMed
        11. Gao FB, Taylor JP. RNA-binding proteins in neurological disease. Brain Res. 2012 Jun 26; 1462:1-2.
          View in: PubMed
        12. Gascon E, Gao FB. Cause or Effect: Misregulation of microRNA Pathways in Neurodegeneration. Front Neurosci. 2012; 6:48.
          View in: PubMed
        13. Lee JA, Gao FB. Neuronal Functions of ESCRTs. Exp Neurobiol. 2012 Mar; 21(1):9-15.
          View in: PubMed
        14. Sun K, Westholm JO, Tsurudome K, Hagen JW, Lu Y, Kohwi M, Betel D, Gao FB, Haghighi AP, Doe CQ, Lai EC. Neurophysiological Defects and Neuronal Gene Deregulation in Drosophila mir-124 Mutants. PLoS Genet. 2012 Feb; 8(2):e1002515.
          View in: PubMed
        15. Almeida S, Delaloy C, Liu L, Gao FB. Protocols for Investigating microRNA Functions in Human Neural Progenitor Cells. Methods Mol Biol. 2012; 916:387-402.
          View in: PubMed
        16. Almeida S, Zhou L, Gao FB. Progranulin, a glycoprotein deficient in frontotemporal dementia, is a novel substrate of several protein disulfide isomerase family proteins. PLoS One. 2011; 6(10):e26454.
          View in: PubMed
        17. Lee JA, Liu L, Javier R, Kreitzer AC, Delaloy C, Gao FB. ESCRT-III subunits Snf7-1 and Snf7-2 differentially regulate transmembrane cargos in hESC-derived human neurons. Mol Brain. 2011; 4:37.
          View in: PubMed
        18. Xu XL, Zong R, Li Z, Biswas MH, Fang Z, Nelson DL, Gao FB. FXR1P But Not FMRP Regulates the Levels of Mammalian Brain-Specific microRNA-9 and microRNA-124. J Neurosci. 2011 Sep 28; 31(39):13705-9.
          View in: PubMed
        19. Kuo TC, Chen CT, Baron D, Onder TT, Loewer S, Almeida S, Weismann CM, Xu P, Houghton JM, Gao FB, Daley GQ, Doxsey S. Midbody accumulation through evasion of autophagy contributes to cellular reprogramming and tumorigenicity. Nat Cell Biol. 2011; 13(10):1214-23.
          View in: PubMed
        20. Yuva-Aydemir Y, Simkin A, Gascon E, Gao FB. MicroRNA-9: functional evolution of a conserved small regulatory RNA. RNA Biol. 2011 Jul 1; 8(4):557-64.
          View in: PubMed
        21. Gao FB. Context-dependent functions of specific microRNAs in neuronal development. Neural Dev. 2010; 5:25.
          View in: PubMed
        22. Delaloy C, Gao FB. A new role for microRNA-9 in human neural progenitor cells. Cell Cycle. 2010 Aug 1; 9(15):2913-4.
          View in: PubMed
        23. Jiao J, Herl LD, Farese RV, Gao FB. MicroRNA-29b regulates the expression level of human progranulin, a secreted glycoprotein implicated in frontotemporal dementia. PLoS One. 2010; 5(5):e10551.
          View in: PubMed
        24. Delaloy C, Liu L, Lee JA, Su H, Shen F, Yang GY, Young WL, Ivey KN, Gao FB. MicroRNA-9 coordinates proliferation and migration of human embryonic stem cell-derived neural progenitors. Cell Stem Cell. 2010 Apr 2; 6(4):323-35.
          View in: PubMed
        25. Lee JA, Liu L, Gao FB. Autophagy defects contribute to neurodegeneration induced by dysfunctional ESCRT-III. Autophagy. 2009 Oct; 5(7):1070-2.
          View in: PubMed
        26. Lu Y, Ferris J, Gao FB. Frontotemporal dementia and amyotrophic lateral sclerosis-associated disease protein TDP-43 promotes dendritic branching. Mol Brain. 2009; 2(1):30.
          View in: PubMed
        27. Ahmad ST, Sweeney ST, Lee JA, Sweeney NT, Gao FB. Genetic screen identifies serpin5 as a regulator of the toll pathway and CHMP2B toxicity associated with frontotemporal dementia. Proc Natl Acad Sci U S A. 2009 Jul 21; 106(29):12168-73.
          View in: PubMed
        28. Lee JA, Gao FB. Inhibition of autophagy induction delays neuronal cell loss caused by dysfunctional ESCRT-III in frontotemporal dementia. J Neurosci. 2009 Jul 1; 29(26):8506-11.
          View in: PubMed
        29. Lee JA, Gao FB. ESCRT, autophagy, and frontotemporal dementia. BMB Rep. 2008 Dec 31; 41(12):827-32.
          View in: PubMed
        30. Xu XL, Li Y, Wang F, Gao FB. The steady-state level of the nervous-system-specific microRNA-124a is regulated by dFMR1 in Drosophila. J Neurosci. 2008 Nov 12; 28(46):11883-9.
          View in: PubMed
        31. Lu Y, Wang F, Li Y, Ferris J, Lee JA, Gao FB. The Drosophila homologue of the Angelman syndrome ubiquitin ligase regulates the formation of terminal dendritic branches. Hum Mol Genet. 2009 Feb 1; 18(3):454-62.
          View in: PubMed
        32. Lee JA, Gao FB. Regulation of Abeta pathology by beclin 1: a protective role for autophagy? J Clin Invest. 2008 Jun; 118(6):2015-8.
          View in: PubMed
        33. Delaloy C, Gao FB. microRNA-9 multitasking near organizing centers. Nat Neurosci. 2008 Jun; 11(6):625-6.
          View in: PubMed
        34. Lee JA, Gao FB. Roles of ESCRT in autophagy-associated neurodegeneration. Autophagy. 2008 Feb 16; 4(2):230-2.
          View in: PubMed
        35. Gao FB. Posttranscriptional control of neuronal development by microRNA networks. Trends Neurosci. 2008 Jan; 31(1):20-6.
          View in: PubMed
        36. Gao FB. Molecular and cellular mechanisms of dendritic morphogenesis. Curr Opin Neurobiol. 2007 Oct; 17(5):525-32.
          View in: PubMed
        37. Lee JA, Beigneux A, Ahmad ST, Young SG, Gao FB. ESCRT-III dysfunction causes autophagosome accumulation and neurodegeneration. Curr Biol. 2007 Sep 18; 17(18):1561-7.
          View in: PubMed
        38. Li Y, Wang F, Lee JA, Gao FB. MicroRNA-9a ensures the precise specification of sensory organ precursors in Drosophila. Genes Dev. 2006 Oct 15; 20(20):2793-805.
          View in: PubMed
        39. Sweeney NT, Brenman JE, Jan YN, Gao FB. The coiled-coil protein shrub controls neuronal morphogenesis in Drosophila. Curr Biol. 2006 May 23; 16(10):1006-11.
          View in: PubMed
        40. Tassetto M, Gao FB. Transcriptional control of dendritic patterning in Drosophila neurons. Genome Biol. 2006; 7(7):225.
          View in: PubMed
        41. Li W, Li Y, Gao FB. Abelson, enabled, and p120 catenin exert distinct effects on dendritic morphogenesis in Drosophila. Dev Dyn. 2005 Nov; 234(3):512-22.
          View in: PubMed
        42. Li W, Wang F, Menut L, Gao FB. BTB/POZ-zinc finger protein abrupt suppresses dendritic branching in a neuronal subtype-specific and dosage-dependent manner. Neuron. 2004 Sep 16; 43(6):823-34.
          View in: PubMed
        43. Xu K, Bogert BA, Li W, Su K, Lee A, Gao FB. The fragile X-related gene affects the crawling behavior of Drosophila larvae by regulating the mRNA level of the DEG/ENaC protein pickpocket1. Curr Biol. 2004 Jun 22; 14(12):1025-34.
          View in: PubMed
        44. Li J, Li W, Calhoun HC, Xia F, Gao FB, Li WX. Patterns and functions of STAT activation during Drosophila embryogenesis. Mech Dev. 2003 Dec; 120(12):1455-68.
          View in: PubMed
        45. Lee A, Li W, Xu K, Bogert BA, Su K, Gao FB. Control of dendritic development by the Drosophila fragile X-related gene involves the small GTPase Rac1. Development. 2003 Nov; 130(22):5543-52.
          View in: PubMed
        46. Li W, Gao FB. Actin filament-stabilizing protein tropomyosin regulates the size of dendritic fields. J Neurosci. 2003 Jul 16; 23(15):6171-5.
          View in: PubMed
        47. Gao FB, Bogert BA. Genetic control of dendritic morphogenesis in Drosophila. Trends Neurosci. 2003 May; 26(5):262-8.
          View in: PubMed
        48. Gao FB. Understanding fragile X syndrome: insights from retarded flies. Neuron. 2002 Jun 13; 34(6):859-62.
          View in: PubMed
        49. Tokumoto YM, Apperly JA, Gao FB, Raff MC. Posttranscriptional regulation of p18 and p27 Cdk inhibitor proteins and the timing of oligodendrocyte differentiation. Dev Biol. 2002 May 1; 245(1):224-34.
          View in: PubMed
        50. Brenman JE, Gao FB, Jan LY, Jan YN. Sequoia, a tramtrack-related zinc finger protein, functions as a pan-neural regulator for dendrite and axon morphogenesis in Drosophila. Dev Cell. 2001 Nov; 1(5):667-77.
          View in: PubMed
        51. Gao FB, Kohwi M, Brenman JE, Jan LY, Jan YN. Control of dendritic field formation in Drosophila: the roles of flamingo and competition between homologous neurons. Neuron. 2000 Oct; 28(1):91-101.
          View in: PubMed
        52. Gao FB, Brenman JE, Jan LY, Jan YN. Genes regulating dendritic outgrowth, branching, and routing in Drosophila. Genes Dev. 1999 Oct 1; 13(19):2549-61.
          View in: PubMed
        53. Gao FB, Apperly J, Raff M. Cell-intrinsic timers and thyroid hormone regulate the probability of cell-cycle withdrawal and differentiation of oligodendrocyte precursor cells. Dev Biol. 1998 May 1; 197(1):54-66.
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        54. Raff MC, Durand B, Gao FB. Cell number control and timing in animal development: the oligodendrocyte cell lineage. Int J Dev Biol. 1998; 42(3):263-7.
          View in: PubMed
        55. Gao FB. Messenger RNAs in dendrites: localization, stability, and implications for neuronal function. Bioessays. 1998 Jan; 20(1):70-8.
          View in: PubMed
        56. Gao FB, Raff M. Cell size control and a cell-intrinsic maturation program in proliferating oligodendrocyte precursor cells. J Cell Biol. 1997 Sep 22; 138(6):1367-77.
          View in: PubMed
        57. Gao FB, Durand B, Raff M. Oligodendrocyte precursor cells count time but not cell divisions before differentiation. Curr Biol. 1997 Feb 1; 7(2):152-5.
          View in: PubMed
        58. Durand B, Gao FB, Raff M. Accumulation of the cyclin-dependent kinase inhibitor p27/Kip1 and the timing of oligodendrocyte differentiation. EMBO J. 1997 Jan 15; 16(2):306-17.
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        59. Gao FB, Keene JD. Hel-N1/Hel-N2 proteins are bound to poly(A)+ mRNA in granular RNP structures and are implicated in neuronal differentiation. J Cell Sci. 1996 Mar; 109 ( Pt 3):579-89.
          View in: PubMed
        60. Gao FB, Carson CC, Levine T, Keene JD. Selection of a subset of mRNAs from combinatorial 3' untranslated region libraries using neuronal RNA-binding protein Hel-N1. Proc Natl Acad Sci U S A. 1994 Nov 8; 91(23):11207-11.
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        61. Levine TD, Gao F, King PH, Andrews LG, Keene JD. Hel-N1: an autoimmune RNA-binding protein with specificity for 3' uridylate-rich untranslated regions of growth factor mRNAs. Mol Cell Biol. 1993 Jun; 13(6):3494-504.
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