Paul J. Hagerman, M.D., Ph.D.

Professor, Department of Biochemistry and Molecular Medicine, School of Medicine

University of California, Davis
4455A Tupper Hall
Davis, CA 95616
E-mail:  pjhagerman@ucdavis.edu

Dr. Hagerman, a molecular biologist with particular expertise in nucleic acid biochemistry, was recruited to the M.I.N.D. Institute and the Department of Biological Chemistry from the University of Colorado School of Medicine in December. He has spearheaded development of the M.I.N.D. Institute's new $1 million neurodevelopmental genomics laboratory, and will take the lead in developing a comprehensive biomarkers research program. The goal of the biomarkers program is to identify biochemical identifiers (markers) of autism and other neurodevelopmental disorders. Such biomarkers will be useful in the short term to identify children who may be predisposed to develop autism; however, the ultimate goal of the program is the development of more effective treatments for autism and related disorders. Dr. Hagerman received both his M.D. and Ph.D. degrees from Stanford University School of Medicine in 1977. This was followed by a three year Leukemia Society Fellowship at UCSD, where he began his studies of nucleic acid structure. He joined the University of Colorado in 1980, where he remained prior to joining the UC Davis faculty. Hagerman is currently on the scientific advisory board of the Muscular Dystrophy Association, and recently shifted toward the study of the molecular biology of neurodevelopmental disorders, with particular emphasis on fragile X syndrome, the leading heritable form of mental retardation. Since joining the Davis faculty, Dr. Hagerman has expanded his research efforts to include investigations of the underlying biochemical and genetic causes of autism.

Ph.D. Stanford University School of Medicine, Palo Alto, California
M.D. Stanford University School of MedicinePalo Alto, California

Garcia Arocena D, Breece, KE, Hagerman PJ. Distribution of CGG repeat sizes within the fragile X mental retardation 1 (FMR1) homologue in a non-human primate population. Hum Genet 113, 371-76, 2003. This study demonstrated that the distribution of CGG repeat sizes was essentially identical in non-human primates to that in humans, indicating that CGG repeat variability – and expansion – precedes the hominid radiation.

Geller SC, Gregg JP, Hagerman P, Rocke DM. Transformation and Normalization of Oligonucleotide Microarray Data. Bioinformatics. 19, 1817-1823, 2003. A new analytical tool was developed to facilitate the analysis of microarray data.

Tassone F, Hagerman P. Expression of the FMR1 gene. Cytogenet Gen Res 100(1-4): 124-128, 2003. A review of the factors governing the expression of the fragile X mental retardation 1 gene, the gene responsible for the leading heritable form of mental retardation.

Chen LS, Tassone F, Sahota P, Hagerman PJ. The (CGG)n repeat element within the 5' untranslated region of the FMR1 message provides both positive and negative cis effects on in vivo translation of a downstream reporter. Hum Mol Genet 12: 3067-74, 2003. This investigation demonstrated that the expression of the fragile X gene also is regulated at the level of translation in a manner that depends on the 5’ untranslated region of the FMR1 message. Small numbers of CGG repeats in the gene lead to translational activation, whereas larger numbers cause inhibition of translation.

Hagerman PJ, Greco CM, Hagerman RJ. A cerebellar tremor/ataxia syndrome among fragile X premutation carriers. Cytogenet Genome Res 100: 206-12, 2003. Review of a newly-discovered neurodegenerative disorder in older adults that is caused by the same fragile X gene that gives rise to a neurodevelopmental disorder in childhood.

Leehey MA, Munholz RP, Lang AE, Bruanberg JA, Grisby J, Greco C, Jacquemont S, Tassone F, Lozano AM, Hagerman PJ, Hagerman RJ.  The Fragile X Premutation Presenting as Essential Tremor.  Arch Neurol 60: 117-212, 2003. This is a case report of two adult males who presented with essential tremor, but they really had FXTAS (Fragile X-associated Tremor/Ataxia Syndrome). The course of the syndrome, as well as problems associated with surgery in one of the cases is discussed.

Hagerman PJ, Hagerman RJ. Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS). Ment Retard Dev Disabil Res Rev 10:25-30, 2004.  Paper reports the effect of this “toxic RNA gain of function” on the brain that may lead to neurological problems and discusses involvement in both children and adults.

Hagerman PJ and Hagerman RJ.  The Fragile-X Premutation: A Maturing Perspective.  Am J Hum Genet 74:805-816, 2004. Paper outlines the pathophysiology of elevated mRNA relative to brain damage.

Hagerman RJ, Leavitt BT, Farzin F, Jacquemont S, Greco CM, Brunberg JA, Tassone F, Hessl D, Harris SW, Zhang L, Jardini T, Gane LW, Ferranti J, Ruiz L, Leehey MA, Grigsby J, and Hagerman PJ.  Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS) in Females with the FMR1 Premutation. Am J Hum Genet 74:1051-1056, 2004. Reports study demonstrating that older females with the premutation may also develop FXTAS.

Jacquemont S, Hagerman RJ, Leehey MA, Hall DA, Levine RA, Brunberg JA, Zhang Lin, Jardini T, Gane LW, Harris SW, Herman K, Grigsby J, Greco C, Berry-Kravis E, Tassone F, Hagerman PJ . Penetrance of the fragile X-associated tremor/ataxia syndrome (FXTAS) in a premutation carrier population: Initial results from a California family-based study. JAMA 291(4):460-469, 2004.  The fragile X premutation, which is associated with autism in some carriers, frequently leads to neurological problems in grandfathers.

Jacquemont S, Farzin F, Hall D, Leehey M, Tassone F, Gane L, Zhang L, Grigsby J, Jardini T, Lewin F, Berry-Kravis E, Hagerman PJ, Hagerman RJ.  Aging in Individuals with the FMR1 Mutation. Am J Mental Retardation 109(2):154-164, 2004. Paper reports the aging and the neurological problems that occur in those with the fragile X mutation.

Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS), 11th International Workshop on Fragile X Syndrome and X-Linked Mental Retardation, Cyprus, “August 2003.

New developments in fragile X research, 15th Annual Symposium, European Academy of Childhood Disability, Oslo, Norway, September 2003.

Neurodevelopment to Neurodegeneration: Two Faces of the Fragile X Gene, Waisman Center, University of Wisconsin - Madison,  Madison, WI, October 2003.

Intranuclear neuronal inclusions in two female carriers of the fragile X permutation, American Society of Human Genetics, Los Angeles, October 2003.

Research on Fragile X children leads to the recognition of a new neurodegenerative syndrome in their grandfathers, Presidential Symposium, Gerontological Society of America, San Diego, CA, October 2003.

Molecular and clinical aspects of fragile X syndrome and related disorders, Faculty of Medicine and Health Sciences, United Arab Emirates University, Dubai, UAE, January 2004.

Fragile X-associated tremor/ataxia syndrome: an aging face of the fragile X gene, 4th International Conference on Unstable Microsatellites and Human Disease, Banff, BC, February 2004.

Fragile X-associated tremor/ataxia syndrome: an aging face of the fragile X gene, Grand Rounds: Frontiers in Neuroscience, Department of Neurology, UCSF, San Francisco, CA, March 2004.

The fragile X gene: Distinct molecular and neuropathologic mechanisms give rise to two separate syndromes, Fragile-X Research Emphasis Area Meeting, Seattle, WA, March 2004.

A newly-discovered neurological disorder of aging - what our children teach us, and From Neurodevelopment to Neurodegeneration: two faces of the fragile X gene, University of Minnesota, Duluth, Duluth, MN, April 2004.

Tremor and Balance: What Our Children Teach Us,  American Association of Neurologists, San Francisco, CA, April 2004.

Tremor and Balance: What Our Children Teach Us, Future Faire, UCDMC, Sacramento, CA, May 2004.

Fragile X Syndrome and FXTAS: Two Faces of the FMR1 Gene , Fragile X: State of the Science, NICHD/NIH meeting, Washington DC, June 2004.

Fragile X-associated Tremor/Ataxia Syndrome, 9th Annual National Fragile X Foundation Conference, Washington DC, June 2004.

Principal Investigator: Expression of the Fragile X Gene, NICHD, 4/01/02-3/31/06, $372,500 annual direct. This project is designed to examine the mechanisms underlying both the silencing of the FMR1 gene and the increase in FMR1 mRNA observed for carriers of premutation FMR1 alleles.

Principal Investigator: Neurological Phenotype in FMR1 Premutation Carriers, NINDS, 7/01/02-6/30/06, $290,435 annual direct. This project represents a three-center consortium established to determine the relationship between premutation carrier status and a newly described neurological phenotype involving tremor, ataxia, and cognitive decline.

Co-Principal Investigator: Genotype-Phenotype Relationships in Fragile X Families, NICHD, 9/1/01-8/31/06, $394,000 annual direct. This grant will correlate FMRP and other molecular measures with anthropometric, IQ and behavioral measures in families with FXS.  It will also investigate the features of premutation carriers of fragile X syndrome.

Core Director: Environmental Factors in the Etiology of Autism, NIEHS, 9/01/01-8/31/06, $200,000 annual direct. The principal objective of this project is to understand common patterns of dysfunction in autism.

National Institutes of Health, Permanent Reviewers Reserve
Editorial Board, Current Opinion in Structural Biology (Nucleic Acids)
Scientific Advisory Board, Muscular Dystrophy Association
Editorial Advisory Board, Biochemistry
Editorial Board, Journal of Molecular Biology

National Fragile X Foundation established the Hagerman Award for Research in FXTAS to honor Paul and Randi Hagerman