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Michael Wigler
Michael Howard Wigler (born September 3, 1947 in New York) is an American molecular biologist who has directed a laboratory at Cold Spring Harbor Laboratory since 1978 and is a member of the National Academy of Sciences. He is best known for developing methods to genetically engineer animal cells and his contributions to cancer, genomics and autism genetics.
Wigler graduated from Princeton University in 1970, majoring in mathematics, and in 1978 received his PhD from Columbia University in microbiology, and has spent the remainder of his career at Cold Spring Harbor Laboratory (CSHL).
Beginning in the late 1970s, at Columbia University, Wigler, Richard Axel and Saul Silverstein developed methods for engineering animal cells.〔Wigler, M.H., Silverstein, S., Lee, L.S., Pellicer, A., Cheng, Y. and Axel, R. (1977) "Transfer of purified herpes virus thymidine kinase gene to cultured mouse cells." Cell 11: 223-232. PMID 194704; Wigler, M., Pellicer, A., Silverstein, S., Axel, R., Urlaub, G. and Chasin, L. (1979) "DNA mediated transfer of the APRT locus into mammalian cells." Proc. Natl. Acad. Sci. USA 76: 1373-1376. PMID 286319; Wigler, M., Perucho, M., Kurtz, D., Dana, S., Pellicer, A., Axel, R. and Silverstein, S. (1980) "Transformation of mammalian cells with an amplifiable dominant acting gene." Proc. Natl. Acad. Sci. U.S., 77: 3567. PMID 6251468〕 These methods are the basis for many discoveries in mammalian genetics, and the means for producing protein therapeutics such as those used to treat heart disease, cancer and strokes.〔Commercial application of these discoveries follows from Axel-Wigler-Silverstein patent application (U.S. 4,399,216) filed February 20, 1980, entitled, “Process for Inserting DNA into Eucaryotic Cells and for Producing Proteinaceous Materials.” http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=4,399,216.PN.&OS=PN/4,399,216&RS=PN/4,399,216〕
After moving to CSHL, Wigler continued his studies of gene transfer into mammalian cells, exploring the integration of foreign DNA〔Perucho, M., Hanahan, D. and Wigler, M. (1980) "Genetic and physical linkage of exogenous sequences in transformed cells." Cell 22: 309-317. PMID 6253083〕 and its stability of expression in host cells,〔Hanahan, D., Lane, D., Lipsich, L., Wigler, M. and Botchan, M. (1980) "Characteristics of an SV40-plasmid recombinant and its movement into and out of the genome of a murine cell." Cell 21: 127-139. PMID 6250708〕 demonstrating the inheritance of DNA methylation patterns,〔Wigler, M., Levy, D. and Perucho, M. (1981) "The somatic replication of DNA methylation. Cell 24: 33-40. PMID 6263490〕 and isolating the first vertebrate genes,〔Perucho, M., Hanahan, D., Lipsich, L. and Wigler, M. (1980) "Isolation of the chicken thymidine kinase gene by plasmid rescue." Nature 285: 207. PMID 6246445〕 and first human oncogenes,〔Perucho, M., Goldfarb, M., Shimizu, K., Lama, C., Fogh, J. and Wigler, M. (1981) "Human-tumor-derived cell lines contain common and different transforming genes." Cell 27: 467-476. PMID 6101201; Goldfarb, M., Shimizu, K., Perucho, M. and Wigler, M. (1982) "Isolation and preliminary characterization of a human transforming gene from T24 bladder carcinoma cells." Nature 296: 404-409. PMID 7063039〕 using DNA transfer and genetic selection. His laboratory was among the group that first showed the involvement of members of the RAS gene family in human cancer,〔Shimizu, K., Goldfarb, M., Perucho, M. Wigler, M., (1983) "Isolation and preliminary characterization of the transforming gene of a human neuroblastoma cell line." Proc. Natl. Acad. Sci., USA, 80: 383-387. PMID 6300838〕 and that point mutations can activate the oncogenic potential of cellular genes.〔Taparowsky, E., Suard, Y., Fasano, O., Shimizu, K., Goldfarb, M., Wigler, M. (1982) "Activation of the T24 bladder carcinoma transforming gene is linked to a single amino acid change. Nature, 300: 762-765. PMID 7177195〕
Wigler’s laboratory was the first to demonstrate that some regulatory pathways have been so conserved in evolution that yeast can be used as a host to study the function of mammalian genes and in particular genes involved in signal transduction pathways and cancer.〔Powers, S., Kataoka, T., Fasano, O., Goldfarb, M., Strathern, J., Broach, J., and Wigler, M. (1984) "Genes in Saccharomyces cerevisiae encoding proteins with domains homologous to the mammalian ras proteins." Cell, 36: 607-612. PMID 6365329; Kataoka, T., Powers, S., Cameron, S., Fasano, O., Goldfarb, M., Broach, J., and Wigler, M. (1985) "Functional homology of mammalian and yeast RAS genes." Cell, 40: 19-26. PMID 2981628〕 This led to deep insights into RAS function, eventually solving the RAS biochemical pathway in yeasts and humans, and demonstrating the multifunctional nature of this important oncogene.〔Van Aelst, L., Barr, M., Marcus, S., Polverino, A. and Wigler, M. (1993) "Complex formation between RAS and RAF and other protein kinases." Proc. Natl. Acad. Sci. USA, 90 : 6213-6217. PMID 8327501; White, M., Nicolette, C., Minden, A., Polverino, A., Van Aelst, L., Karin, M. and Wigler, M. (1995) "Multiple RAS functions can contribute to mammalian cell transformation." Cell, 80: 533-541. PMID 7867061〕 During this period Wigler's lab published the first use of epitope tagging for protein purification.〔Field, J., Nikawa, J., Broek, D., MacDonald, B., Rodgers, L., Wilson, I.A., Lerner, R.A. and Wigler, M. (1988) "Purification of a RAS -responsive adenylyl cyclase complex from Saccharomyces cerevisiae by use of an epitope addition method." Molecular and Cellular Biology, 8: 2159-2165. PMID 2455217〕
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