Paul Hagerman, MD, PhD

Dr HagermanMD - Stanford University School of Medicine
PhD - Stanford University School of Medicine (Biochemistry)
Professor of Biochemistry and Molecular Medicine
Director, NeuroTherapeutics Research Institute (NTRI)
University of California, Davis, School of Medicine
4303 Tupper Hall
One Shields Ave.
Davis, CA
Office (530) 754-7266
Assist. (530) 754-7270 pjhagerman@ucdavis.edu
http://wizard1.ucdavis.edu
http://www.ucdmc.ucdavis.edu/NTRI

Dr. Hagerman is a molecular biologist with a passionate interest in understanding the basis for neurodevelopmental and neurodegenerative disorders, with specific emphasis on disorders related to the fragile X (FMR1) gene. The Hagerman lab has made a number of important observations related to the mechanism of expression of the FMR1 gene. In 2001, Dr. Hagerman and his wife, Dr. Randi Hagerman, reported their discovery of a new neurological disorder involving tremor and balance problems (fragile X-associated tremor/ataxia syndrome; FXTAS). FXTAS, with features of both Alzheimer's and Parkinson's diseases, may be one of the most common single-gene neurodegenerative disorders among older adult males (and some females) in the general population. FXTAS is one of a growing number of neurodegenerative disorders that are caused by the direct toxic gain-of-function of the expressed mRNA itself. The disorder is caused by the same gene that gives rise to fragile X syndrome, the leading heritable form of mental impairment in children and the leading known single gene associated with autism. Dr. Hagerman believes that the study of fragile X syndrome and FXTAS will lead to a broader understanding of neurodegenerative disorders and developmental disorders of childhood.

The principal goal of the Hagerman laboratory is the development of effective therapies for both FXTAS and fragile X syndrome. Our efforts combine clinical and basic molecular research, the latter involving studies of the regulation of gene expression at the level of transcription and translation.

 

"RNA toxicity" refers to the direct induction/triggering by RNA of a disease process; in the case of FXTAS, this induction is likely the result of one or more proteins interacting with the CGG repeat to produce cellular dysfunction. The term "gain-of-function" refers to some new function of an RNA or protein that is not part of its normal function - for the FMR1 mRNA, this new function is the triggering of the pathogenic process leading to FXTAS, whereas its normal function is to be translated into FMRP