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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 - Graduate School of Biomedical Sciences
      DepartmentTranslational Science

      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 focal atrophy of the frontal and/or temporal lobes and recognized now as the most common form of dementia before the age of 60. Unfortunately, the molecular pathogenesis of FTD remains largely unknown and effective treatments are not available. Recent exciting advances indicate that FTD is often associated with amyotrophic 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 component of ESCRT-III and regulates dendritic morphogenesis. In cultured cortical neurons, we found that dysfunctional ESCRT-III, lacking essential components (such as mSnf7-2, one of the mouse homologs of Shrub) or containing ectopically expressed FTD3-associated mutant CHMP2B, causes dendritic retraction,autophagosome accumulation and eventual neurodegeneration. Through an unbiased genetic screen in a Drosophila modelof FTD3, we identified several genetic modifiers of CHMP2B toxicity in vivo that are currently being characterized. We have also been using Drosophila models to study other FTD genes.

        We have also established patient-specific induced pluripotent stem cells (iPSC) models of FTD with mutations in progranulin, C9ORF72 and other genes. Over the next a few years, we will use a combination of molecular, cellular, and genetic approaches in both Drosophila and iPSCs models to further dissect the pathogenic mechanisms involving these FTD disease genes. Our ultimate goal is to identify common underlying pathogenic pathways as potential targets for therapeutic interventions.

        Another research interest in our laboratory is the microRNA pathway. The roles of this pathway in FTD-associated neurodegeneration will be investigated in detail.



        Rotation Projects

        Project 1: Perform genetic and molecular analysis of disease modifiers identified from our fly models of frontotemporal dementia. 



        Post Docs

        A postdoctoral position is available in the laboratory of Dr. Fen-Biao Gao at the University of Massachusetts Medical School to study molecular pathogenic mechanisms of fronototemporal dementia using Drosophila models (PNAS 2009; Mol. Cell 2013 and others). Candidates with strong work ethics and research experience in Drosophila genetics and molecular biology are encouraged to apply. Interested please send CV to fen-biao.gao@umassmed.edu (Updated on November 6, 2014)



        Bibliographic 
        selected publications
        List All   |   Timeline
        1. Gascon E, Lynch K, Ruan H, Almeida S, Verheyden JM, Seeley WW, Dickson DW, Petrucelli L, Sun D, Jiao J, Zhou H, Jakovcevski M, Akbarian S, Yao WD, Gao FB. Alterations in microRNA-124 and AMPA receptors contribute to social behavioral deficits in frontotemporal dementia. Nat Med. 2014 Nov 17.
          View in: PubMed
        2. Gao FB, Taylor JP. RNA metabolism in neurological disease. Brain Res. 2014 Oct 10; 1584:1-2.
          View in: PubMed
        3. Simkin AT, Bailey JA, Gao FB, Jensen JD. Inferring the Evolutionary History of Primate microRNA Binding Sites: Overcoming Motif Counting Biases. Mol Biol Evol. 2014 Jul; 31(7):1894-901.
          View in: PubMed
        4. 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 Mar-Jun; 28(1-2):30-40.
          View in: PubMed
        5. 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
        6. 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
        7. 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
        8. 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 24; 52(2):264-71.
          View in: PubMed
        9. 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 Sep; 126(3):385-99.
          View in: PubMed
        10. 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):5352-61.
          View in: PubMed
        11. 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. 2013; 2(22):218-225.
        12. 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 25; 2(4):789-98.
          View in: PubMed
        13. 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 Dec; 48(3):391-8.
          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; 2(8):e1002515.
        15. Lee JA, Gao FB. Neuronal Functions of ESCRTs. Exp Neurobiol. 2012; 1(21):9-15.
        16. Gascon E, Gao FB. Cause or Effect: Misregulation of microRNA Pathways in Neurodegeneration. Front Neurosci. 2012; (6):48.
        17. Gao FB, Taylor JP. RNA-binding proteins in neurological disease. Brain Res. 2012; (1462):1-2.
        18. 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.
        19. 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
        20. 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
        21. 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 Oct; 13(10):1214-23.
          View in: PubMed
        22. Yuva-Aydemir Y, Simkin A, Gascon E, Gao FB. MicroRNA-9: functional evolution of a conserved small regulatory RNA. RNA Biol. 2011 Jul-Aug; 8(4):557-64.
          View in: PubMed
        23. 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; 39(31):13705-13709.
        24. Gao FB. Context-dependent functions of specific microRNAs in neuronal development. Neural Dev. 2010; 5:25.
          View in: PubMed
        25. 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
        26. 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
        27. 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
        28. 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
        29. Lu Y, Ferris J, Gao FB. Frontotemporal dementia and amyotrophic lateral sclerosis-associated disease protein TDP-43 promotes dendritic branching. Mol Brain. 2009; 2:30.
          View in: PubMed
        30. 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
        31. Lee JA, Gao FB. Inhibition of autophagy induction delays neuronal cell loss caused by dysfunctional ESCRT-III in frontotemporal dementia. J Neurosci. 2009; 26(29):8506-8511.
        32. Lee JA, Gao FB. ESCRT, autophagy, and frontotemporal dementia. BMB Rep. 2008 Dec 31; 41(12):827-32.
          View in: PubMed
        33. 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
        34. 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
        35. 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
        36. Delaloy C, Gao FB. microRNA-9 multitasking near organizing centers. Nat Neurosci. 2008 Jun; 11(6):625-6.
          View in: PubMed
        37. Lee JA, Gao FB. Roles of ESCRT in autophagy-associated neurodegeneration. Autophagy. 2008 Feb; 4(2):230-2.
          View in: PubMed
        38. Gao FB. Posttranscriptional control of neuronal development by microRNA networks. Trends Neurosci. 2008 Jan; 31(1):20-6.
          View in: PubMed
        39. Gao FB. Molecular and cellular mechanisms of dendritic morphogenesis. Curr Opin Neurobiol. 2007 Oct; 17(5):525-32.
          View in: PubMed
        40. Lee JA, Beigneux A, Ahmad ST, Young SG, Gao FB. ESCRT-III dysfunction causes autophagosome accumulation and neurodegeneration. Curr Biol. 2007; 18(17):1561-1567.
        41. 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
        42. Sweeney NT, Brenman JE, Jan YN, Gao FB. The coiled-coil protein shrub controls neuronal morphogenesis in Drosophila. Curr Biol. 2006; 10(16):1006-1011.
        43. Tassetto M, Gao FB. Transcriptional control of dendritic patterning in Drosophila neurons. Genome Biol. 2006; 7(7):225.
          View in: PubMed
        44. 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
        45. 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
        46. 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
        47. 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
        48. 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
        49. Gao FB, Bogert BA. Genetic control of dendritic morphogenesis in Drosophila. Trends Neurosci. 2003 May; 26(5):262-8.
          View in: PubMed
        50. 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
        51. 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; 5(1):667-677.
        52. 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
        53. 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
        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, 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; 1(197):54-66.
        57. 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.
          View in: PubMed
        58. Gao FB, Durand B, Raff M. Oligodendrocyte precursor cells count time but not cell divisions before differentiation. Curr Biol. 1997; 2(7):152-155.
        59. Gao FB, Raff M. Cell size control and a cell-intrinsic maturation program in proliferating oligodendrocyte precursor cells. J Cell Biol. 1997; 6(138):1367-1377.
        60. 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
        61. 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; 23(91):1207-1211.
        62. 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; 6(13):3494-3504.
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