The Basic Biology of Aging at the University of Washington
Lawrence A. Loeb, M.D., Ph.D.

Biosketch Information
Email: laloeb@u.washington.edu

Dr. Loeb’s laboratory concentrates on the pathogenesis and treatment of cancers. On one project the group seeks to find the contribution of oxygen free radicals to pancreatic and colon cancers. On another project they want to identify and produce new mutant enzymes that enhance cellular resistance to specific DNA damaging agents used extensively in cancer chemotherapy. In a related project they are studying how reactive oxygen species contribute to DNA damage, mutations, and cancer.

Within the Comparative Mouse Genomics Center, they are focusing on the enzymatic activity of DNA repair genes that are polymorphic in the human population to determine which polymorphisms are associated with genomic instability.

Dr. Loeb’s laboratory is creating mutator mice by several different strategies, altering mouse DNA polymerases in order to manipulate the rate of somatic mutation and possibly the rate of aging. They are studying human genetic variations and “constructing” mice to mimic the variations. They are studying the specificity of oxygen-DNA damage and mutagenesis to determine the contribution of oxygen free radicals to aging. As part of the Genetic Instability of Werner Syndrome project, they are probing the biochemistry of the Werner's helicase.

Dr. Loeb has held several positions during his long, productive career: Professor of Pathology since 1978, Adjunct Professor of Biochemistry, 1978-1993 and Professor, Joint Appointment, Biochemistry, 1993-present, and Director, Medical Scientist Training Program, Pathology, 1988- present. In addition to his many honors and publications, he serves as president, Environmental Mutagen Society, 2001-2003, and held a Burroughs-Wellcome Visiting Professorship in Basic Sciences in 2002.

Selected Relevant Publications
Encell LP, Landis DM, Loeb LA. Improving enzymes for cancer gene therapy. Nat Biotech 17:143-147, 1999.

Fry M, Loeb LA. Human Werner syndrome DNA helicase unwinds tetrahelical structures of the fragile X syndrome repeat sequence d(CGG)n. J Biol Chem 274:12797-12802, 1999.

Kamath-Loeb AS, Johansson E, Burgers PMJ, Loeb LA. Functional interaction between the Werner syndrome protein and DNA polymerase. Proc Natl Acad Sci USA 97:4603-4608, 2000.

Loeb KR, Loeb LA. Significance of multiple mutations in cancer. Carcinogenesis 21:379-385, 2000.

Shen J-C, Loeb LA. Werner syndrome exonuclease catalyzes structure-dependent degradation of DNA. Nucleic Acids Res 28:3260-3268, 2000.

Patel PH, Loeb LA. Getting a grip on how DNA polymerases function. Nat Struct Biol 8:656-659, 2001.

Shen J-C, Loeb LA. Unwinding the molecular basis of the Werner syndrome. Mech Aging Dev 122:921-944, 2001.

Jackson A, Loeb LA. The contribution of endogenous sources of DNA damage to the multiple mutations in cancer. Mutat Res 477:7-21, 2001.

Loeb LA. A mutator phenotype in cancer. Cancer Res 61:3230-3239, 2001.

Glick E, Vigna KL, Loeb LA. Mutations in human DNA polymerase eta motif II alter bypass of DNA lesions. EMBO J 20:7303-7312, 2001.