Paul J. Hagerman
Professor
pjhagerman@ucdavis.edu
Biochemistry and Molecular Medicine
Office
4455A Tupper Hall
+1 530 754 7266
Degrees:
1977
MD
Stanford
1977
PhD
Stanford
Research Contribution to Society:
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. I am currently the PI of an NIH Roadmap Interdisciplinary Research Consortium (~20 investigators) that is focused on translational research on FXTAS.
Awards:
2011 UC Davis School of Medicine Research Award
Department and Center Affiliations:
NeuroTherapeutics Research Institute (NTRI)
Biochemistry and Molecular Medicine, School of Medicine
MIND Institute
Professional Societies:
Society for the Study of Behavioral Phenotypes
Society for Neuroscience
American Society of Human Genetics
CBS Graduate Group Affiliations:
Genetics
Biochemistry, Molecular, Cellular and Developmental Biology
Neuroscience
Specialties / Focus:
Biochemistry, Molecular, Cellular and Developmental Biology
Molecular Medicine
Genetics
Human Genetics
Publications:
Last updated 8/24/2011
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
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. PMC3046292
Leehey MA and Hagerman PJ (2011) Fragile X-associated tremor/ataxia syndrome. Handb Clin Neurol 103:373-386.
Hunsaker MR, Greco CM, Tassone F, Berman RF, Willemsen R, Hagerman RJ and Hagerman PJ (2011) Rare intranuclear inclusions in the brains of 3 older adult males with fragile X syndrome: implications for the spectrum of fragile X-associated disorders. J Neuropathol Exp Neurol 70:462-469. PMC3109086
Hunsaker MR, Greco CM, Spath MA, Smits AP, Navarro CS, Tassone F, Kros JM, Severijnen LA, Berry-Kravis EM, Berman RF, Hagerman PJ, Willemsen R, Hagerman RJ and Hukema RK (2011) Widespread non-central nervous system organ pathology in fragile X premutation carriers with fragile X-associated tremor/ataxia syndrome and CGG knock-in mice. Acta Neuropathol.
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
Hessl D, Wang JM, Schneider A, Koldewyn K, Le L, Iwahashi C, Cheung K, Tassone F, Hagerman PJ and Rivera SM (2011) Decreased fragile X mental retardation protein expression underlies amygdala dysfunction in carriers of the fragile X premutation. Biol Psychiatry.
Hall DA, Berry-Kravis E, Zhang W, Tassone F, Spector E, Zerbe G, Hagerman PJ, Ouyang B and Leehey MA (2011) FMR1 gray-zone alleles: Association with Parkinson's disease in women? Mov Disord.
Hagerman R, Au J and Hagerman P (2011) FMR1 premutation and full mutation molecular mechanisms related to autism. J Neurodev Disord.
Greco CM, Navarro CS, Hunsaker MR, Maezawa I, Shuler JF, Tassone F, Delany M, Au JW, Berman RF, Jin LW, Schumann C, Hagerman PJ and Hagerman RJ (2011) Neuropathologic features in the hippocampus and cerebellum of three older men with fragile X syndrome. Mol Autism 2:2. PMC3045897
Cunningham CL, Martínez Cerdeño 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 [Available on 2012/1/1]
Chen L, Hadd AG, Sah S, Houghton JF, Filipovic-Sadic S, Zhang W, Hagerman PJ, Tassone F and Latham GJ (2011) High-resolution methylation polymerase chain reaction for fragile X analysis: evidence for novel FMR1 methylation patterns undetected in Southern blot analyses. Genet Med 13:528-538.
Sellier C, Rau F, Liu Y, Tassone F, Hukema RK, Gattoni R, Schneider A, Richard S, Willemsen R, Elliott DJ, Hagerman PJ and Charlet-Berguerand N (2010) Sam68 sequestration and partial loss of function are associated with splicing alterations in FXTAS patients. EMBO J 29:1248-1261. PMC2857464 [Available on 2011/4/7]
Ross-Inta C, Omanska-Klusek A, Wong S, Barrow C, Garcia-Arocena D, Iwahashi C, Berry-Kravis E, Hagerman RJ, Hagerman PJ and Giulivi C (2010) Evidence of mitochondrial dysfunction in fragile X-associated tremor/ataxia syndrome. Biochem J 429:545-552.
Paul R, Pessah IN, Gane L, Ono M, Hagerman PJ, Brunberg JA, Tassone F, Bourgeois JA, Adams PE, Nguyen DV and Hagerman R (2010) Early onset of neurological symptoms in fragile X premutation carriers exposed to neurotoxins. Neurotoxicology 31:399-402.
Hagerman R, Hoem G and Hagerman P (2010) Fragile X and autism: Intertwined at the molecular level leading to targeted treatments. Molec Autism 1:12. PMC2954865
Garcia-Arocena D, Yang JE, Brouwer JR, Tassone F, Iwahashi C, Berry-Kravis EM, Goetz CG, Sumis AM, Zhou L, Nguyen DV, Campos L, Howell E, Ludwig A, Greco C, Willemsen R, Hagerman RJ and Hagerman PJ (2010) Fibroblast phenotype in male carriers of FMR1 premutation alleles. Hum Mol Genet 19:299-312. PMC2796892
Garcia-Arocena D and Hagerman PJ (2010) Advances in understanding the molecular basis of FXTAS. Hum Mol Genet 19:R83-89.
Filipovic-Sadic S, Sah S, Chen L, Krosting J, Sekinger E, Zhang W, Hagerman PJ, Stenzel TT, Hadd AG, Latham GJ and Tassone F (2010) A novel FMR1 PCR method for the routine detection of low abundance expanded alleles and full mutations in fragile X syndrome. Clin Chem 56:399-408.
Chen Y, Tassone F, Berman RF, Hagerman PJ, Hagerman RJ, Willemsen R and Pessah IN (2010) Murine hippocampal neurons expressing Fmr1 gene premutations show early developmental deficits and late degeneration. Hum Mol Genet 19:196-208. PMC2792156
Chen L, Hadd A, Sah S, Filipovic-Sadic S, Krosting J, Sekinger E, Pan R, Hagerman PJ, Stenzel TT, Tassone F and Latham GJ (2010) An information-rich CGG repeat primed PCR that detects the full range of fragile X expanded alleles and minimizes the need for Southern blot analysis. J Mol Diagn 12:589-600. PMC2928422
Adams PE, Adams JS, Nguyen DV, Hessl D, Brunberg JA, Tassone F, Zhang W, Koldewyn K, Rivera SM, Grigsby J, Zhang L, Decarli C, Hagerman PJ and Hagerman RJ (2010) Psychological symptoms correlate with reduced hippocampal volume in fragile X premutation carriers. Am J Med Genet B Neuropsychiatr Genet 153B:775-785.
Laboratory Personnel:
Hagerman Lab
http://wizard1.ucdavis.edu/
Christine Iwahashi
Anna Ludwig (postdoc)
Chris Raske
Erick Loomis (GSR)
Kasia Koscielska (GSR)
Katherine Cheung
Sean Roenspie
Glenda Espinal
Sukhi Brar
Edwin Chuck (GSR)
Jun Yin (postdoc)
Lisa Makhoul (asst)
Key Words:
Fragile X Syndrome, FXTAS, Neurodegeneration, FMR1, gene expression, CGG repeats