Associate Editor : Lawrence A. Loeb, M.D., Ph.D

Associate Editor Lawrence A. Loeb, M.D., Ph.D. Dr. Lawrence A. Loeb is the director of the Joseph Gottstein Memorial Cancer Re- search Laboratory at The University of Wa- shington School of Medicine. He is also a professor in the De- partments of Pathol- ogy and Biochemistry and director of The University of Wa- shington's Medical Scientist Training Program. Dr. Loeb received his M.D. degree from N.Y.U.-Bellevue Medical School in 1961 and his Ph.D. from The University of California at Berkeley in 1964. He was a member of the Fox Chase Cancer Center and a Professor of Pathology at The University of Pennsylvania prior to joining The University of Washington in 1978. Dr. Loeb is a past president of the American Association for Cancer Research and is president elect of the Environmental Mutagen Society. Dr. Loeb is internationally known for his studies on the fidelity of DNA replication, for the concept of a mutator phenotype in cancer, and for the use of random nucleotide sequences to create new mutant enzymes for gene therapy. The focus of Dr. Loeb's research is to understand how normal human cells replicate their DNA with high accuracy and to determine if this accuracy is diminished in cancer cells. His approach has been to copy DNA in vitro with individual DNA polymerases and then to analyze their replicational fidelity by determining the frequencies and type of mutations that are produced by transfecting the copied DNA into reporter cells. On the basis of the contrast between the high accuracy of DNA replication in normal human cells and the large numbers of chromosomal abnormalities and mutations in most human tumors, Dr. Loeb hypothesized that cancer is manifested by a mutator phenotype. The concept is based on the argument that the spontaneous mutation rate in normal cells is insufficient to account for the multiple mutations in human cancer cells. Recent studies of microsatellite instability by many investiga- tors, both in inherited and in sporadic human tumors, have provided the first strong evidence for a mutator phenotype in cancer. Dr. Loeb and coworkers have pioneered studies on applied molecular evolution. Their idea was to replace specific segments of genes with random nucleotides and to use the power of genetic selection to identify new sequences that encode proteins not present in nature. They utilized this approach to create large numbers of active mutants of a variety of enzymes, including DNA polymerases, HIV reverse transcriptase, DNA methyl- transferase and thymidine kinase. They have isolated more than 3000 novel mutants of herpes thymidine kinase, some of which preferentially phosphorylate gancyclovir or acyclovir and thus offer promise for gene therapy of cancer. Dr. Loeb was a recipient of an Outstanding Investigator Award from the National Cancer Institute (1985±1999). Dr. Loeb is the editor of Cell Biology and Toxicology and also served on the editorial boards for many journals, including Cancer Research, Carcinogenesis, and the Journal of Biological Chemistry. 66 Journal of Experimental Therapeutics and Oncology Vol. 2 2002 D 2002 Blackwell Publishing Inc.

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Associate Editor : Lawrence A. Loeb, M.D., Ph.D