Paul Hagerman

image of Paul Hagerman

Professor

Departments

Biochemistry and Molecular Medicine

Offices and Labs

4455A Tupper Hall
+1 530 754 7266

Degrees

1977 MD Stanford
1977 PhD Stanford

Research Contribution

In 2001, we described our discovery of a hitherto unrecognized neurodegenerative disorder among older adult (premutation) carriers, and we later named this disorder “fragile X-associated tremor/ataxia syndrome (FXTAS). This disorder is one of the most common single-gene, late-onset neurodegenerative disorders (~1/3,000 males over 50 yr in the general population), and our translational research consortium has contributed greatly to its characterization. We currently have the world’s largest clinical population of FXTAS patients. We identified the molecular trigger for FXTAS (RNA toxicity of the expanded-repeat FMR1 mRNA). We view FXTAS as a paradigm for understanding more broadly mechanisms of neurodegeneration.

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.

Awards

2011 UC Davis School of Medicine Research Award

Department and Center Affiliations

Biochemistry and Molecular Medicine, School of Medicine
MIND Institute

ProfessionalSocieties

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

CBS Grad Group Affiliations

Integrated Genetics and Genomics
Biochemistry, Molecular, Cellular and Developmental Biology

Specialties / Focus

Biochemistry, Molecular, Cellular and Developmental Biology
  • Molecular Medicine
Integrated Genetics and Genomics
  • Human Genetics and Genomics

Labs

Hagerman Lab website
  • 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)

Courses

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

Publications

11/14/2015 11:45:14 PM
  • 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