The Basic Biology of Aging at the University of Washington
Raymond Monnat, Jr., Ph.D.

Biosketch Information
Email: monnat@u.washington.edu

Dr. Monnat’s program focuses on the Werner Syndrome, a type I multiple endocrine neoplasia that causes premature aging. His laboratory attempts to characterize genetic instability in Werner cell lines; determine whether loss of WRN helicase function confers genetic instability in human cells; and determine whether WRN protein plays a role in assuring accurate DNA double strand break repair.

The Monnat Laboratory concentrates on generating homing endonuclease variant proteins with the ability to recognize long novel DNA target sites with high sequence specificity; characterizing the functional and structural properties of these variant homing endonuclease proteins; and determining their ability to act on specific gene targets in human cells.

In an additional project, sponsored as one of several projects in a newly formed Virtual Research Institute, the laboratory is investigating the role of homologous recombination functions and proteins in insuring cell survival and genetic stability during aging.

Dr. Monnat is Professor of Pathology and Adjunct Professor of Genetics and Genome Sciences. He is a Scientific Advisory Board Member, Fanconi Anemia Research Fund. He serves as Head, Genome Instability and Mutagenesis Program, Fred Hutchinson/UW Comprehensive Cancer Center. In 1997 he won the Exemplary Leadership in Teaching Award, UW School of Medicine.

Selected Relevant Publications
Argast G, Stephens KM, Emond MJ, Monnat RJ Jr. I-PpoI and I- CreI homing site sequence degeneracy determined by random mutagenesis and sequential in vitro enrichment. J Mol Biol 280:345-353, 1998.

Moser MJ, Oshima J, Monnat RJ Jr. Invited mutation update: WRN mutations in Werner syndrome. Hum Mutation 13:271-279, 1999.

Monnat RJ Jr, Hackmann AFM, Cantrell MA. Generation of highly site-specific DNA double strand breaks in human cells by the homing endonucleases I-PpoI and I-CreI. Biochem Biophys Res Comm 255:88-93, 1999.

Prince PR, Ogburn CE, Moser MJ, Emond MJ, Martin GM, Monnat RJ Jr. Cell fusion corrects the 4-nitroquinoline 1-oxide sensitivity of Werner syndrome fibroblast cell lines. Hum Genet105: 132-138, 1999.

Moser MJ, Kamath-Loeb AS, Jacob JE, Bennett SE, Oshima J, Monnat RJ Jr. WRN helicase expression in Werner syndrome cell lines. Nucleic Acids Res 28:648-654, 2000.

Moser MJ, Bigbee WL, Grant SG, Emond MJ, Langlois RG, Jensen RH, Oshima J, Monnat RJ Jr. Genetic instability and hematologic disease risk in Werner syndrome patients and hetero-zygotes. Cancer Res 60:2492-2496, 2000.

Prince PR, Emond MJ, Monnat RJ Jr. Loss of Werner syndrome protein function promotes aberrant mitotic recombination Genes Dev 15:933-938, 2001.

Colgin LM, Hackmann AFM, Emond MJ, Monnat RJ Jr. The unexpected landscape of in vivosomatic mutation in a human epithelial cell lineage. Proc Natl Acad Sci USA 99:1437-1442, 2001.