Paul J. Hagerman

Paul Hagerman

Position Title
Professor

Unit
Department of Biochemistry and Molecular Medicine, School of Medicine

4455A Tupper Hall
Bio

Research Interests

Molecular genetics of fragile X syndrome and related neurodevelopmental and neurodegenerative disorders

The lab investigates the mechanisms of pathogenesis of fragile X-associated disorders, including fragile X syndrome (FXS), the leading single-gene form of intellectual disability and autism, and fragile X-associated tremor/ataxia syndrome (FXTAS), one of the leading single-gene forms of adult-onset neurodegeneration. Although these disorders are all caused by expansion of the non-coding CGG repeat in the fragile X (FMR1) gene, the mechanisms are entirely different for FXS (epigenetic silencing) and FXTAS (gain-of-function toxicity of the FMR1 mRNA. Research involves both basic molecular mechanisms and human subject-based studies.

Grad Group Affiliations

  • Biochemistry, Molecular, Cellular and Developmental Biology
  • Integrative Genetics and Genomics

Specialties / Focus

  • Human Genetics and Genomics
  • Molecular Medicine

Courses

  • GGG 201C Molecular Genetic Mechanisms of Disease
  • MMI 280 Molecular Pathobiology of Disease

Labs

  • Hagerman Lab http://wizard1.ucdavis.edu/
    • Jun Yi Wang (Postdoc)Jamie Randol(GSR)Katherine Nichole Holm(GSR)Lisa Ma(VetMed/GSR)Glenda Espinal (Lab manager)Lisa Makhoul (Assistant)Mor Alkaslazi(UR)Robert Riestenberg(PostBac)

Honors and Awards

  • 2011 UC Davis School of Medicine Research Award

    Professional Societies

    • Society for the Study of Behavioral Phenotypes
    • American Society of Human Genetics

    Degrees

    • 1977 MD Stanford
    • 1977 PhD Stanford

    Publications

    Hagerman PJ, Hagerman RJ. Fragile X-associated tremor/ataxia syndrome. Ann N Y Acad Sci. 2015 Mar;1338:58-70. doi: 10.1111/nyas.12693. Epub 2015 Jan 26. Review. PubMed PMID: 25622649; PubMed Central PMCID: PMC4363162.

    Ludwig AL, Espinal GM, Pretto DI, Jamal AL, Arque G, Tassone F, Berman RF, Hagerman PJ. CNS expression of murine fragile X protein (FMRP) as a function of CGG-repeat size. Hum Mol Genet. 2014 Jun 15;23(12):3228-38. doi: 10.1093/hmg/ddu032. Epub 2014 Jan 23. PubMed PMID: 24463622; PubMed Central PMCID: PMC4030777.

    Loomis EW, Sanz LA, Chédin F, Hagerman PJ. Transcription-associated R-loop formation across the human FMR1 CGG-repeat region. PLoS Genet. 2014 Apr 17;10(4):e1004294. doi: 10.1371/journal.pgen.1004294. eCollection 2014 Apr. PubMed PMID: 24743386; PubMed Central PMCID: PMC3990486.

    2013 Hagerman R, Hagerman P Advances in clinical and molecular understanding of the FMR1 premutation and fragile X-associated tremor/ataxia syndrome. Lancet Neurol 12 (8):786-798. doi:http://dx.doi.org/10.1016/S1474-4422(13)70125-X

    2013 Sellier C, Freyermuth F, Tabet R, Tran T, He F, Ruffenach F, Alunni V, Moine H, Thibault C, Page A, Tassone F, Willemsen R, Disney Matthew D, Hagerman PJ, Todd PK, Charlet-Berguerand N. Sequestration of DROSHA and DGCR8 by Expanded CGG RNA Repeats Alters MicroRNA Processing in Fragile X-Associated Tremor/Ataxia Syndrome. Cell Reports. doi: 10.1016/j.celrep.2013.02.004

    2013 Loomis EW, Eid JS, Peluso P, Yin J, Hickey L, Rank D, McCalmon S, Hagerman RJ, Tassone F, Hagerman PJ. Sequencing the unsequenceable: Expanded CGG-repeat alleles of the fragile X gene. Genome Res. 23:121-128. PMCID: PMC3530672.

    2012 Liu J, Koscielska KA, Cao Z, Hulsizer S, Grace N, Mitchell G, Nacey C, Githinji J, McGee J, Garcia-Arocena D, Hagerman RJ, Nolta J, Pessah IN, Hagerman PJ. Signaling defects in iPSC-derived fragile X premutation neurons. Hum Molec Genet. 21:3795-805. PMCID: PMC3412379

    2012 Jenkins EC, Tassone F, Ye L, Hoogeveen AT, Brown WT, Hagerman RJ, Hagerman PJ. Reduced telomere length in individuals with FMR1 premutations and full mutations. Am J Med Genet A. 158A:1060-5. PMID: 22489017

    2012 Cao Z, Hulsizer S, Tassone F, Tang HT, Hagerman RJ, Rogawski MA, Hagerman PJ, Pessah IN. Clustered burst firing in FMR1 premutation hippocampal neurons: amelioration with allopregnanolone. Hum Molec Genet. 21:2923-35. PMCID: PMC3373240

    Yrigollen CM, Durbin-Johnson B, Gane L, Nelson DL, Hagerman R, Hagerman PJ and Tassone F (2012) AGG interruptions within the maternal FMR1 gene reduce the risk of offspring with fragile X syndrome. Genet Med 14:729-736.

    Cunningham CL, Martinez Cerdeno V, Navarro Porras E, Prakash AN, Angelastro JM, Willemsen R, Hagerman PJ, Pessah IN, Berman RF and Noctor SC (2011) Premutation CGG-repeat expansion of the Fmr1 gene impairs mouse neocortical development. Hum Mol Genet 20:64-79. PMC3000676

    Hoem G, Raske CR, Garcia-Arocena D, Tassone F, Sanchez E, Ludwig AL, Iwahashi CK, Kumar M, Yang JE and Hagerman PJ (2011) CGG-repeat length threshold for FMR1 RNA pathogenesis in a cellular model for FXTAS. Hum Mol Genet 20:2161-2170. PMC3090194

    Ludwig AL, Hershey JW and Hagerman PJ (2011) Initiation of translation of the FMR1 mRNA occurs predominantly through 5'-end-dependent ribosomal scanning. J Mol Biol 407:21-34. PMCPMC3046292

    Napoli E, Ross-Inta C, Wong S, Omanska-Klusek A, Barrow C, Iwahashi C, Garcia-Arocena D, Sakaguchi D, Berry-Kravis E, Hagerman R, Hagerman PJ and Giulivi C (2011) Altered zinc transport disrupts mitochondrial protein processing/import in fragile X-associated tremor/ataxia syndrome. Hum Mol Genet 20:3079-3092. PMC3131047

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