Michael Wigler

Michael Howard Wigler (born September 3, 1947, New York) graduated Princeton University (1970), majoring in mathematics, and received his PhD from Columbia University in microbiology (1978).

Beginning in the late 1970s, at Columbia University, Wigler, Richard Axel and Saul Silverstein developed methods for engineering animal cells ^[1](9, 11, 13). These methods are the basis for many discoveries in mammalian genetics, and the means for producing medicines used to treat heart disease, cancer and strokes.

After moving to Cold Spring Harbor Laboratory, Wigler continued his studies of gene transfer into mammalian cells, exploring the integration of foreign DNA and its stability of expression in host cells (16, 17), demonstrating the inheritance of DNA methylation patterns (18), and isolating the first vertebrate genes (14), and first human oncogenes (21), 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 (24, 29), and that point mutations can activate the oncogenic potential of cellular genes (22).

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 (31, 36), in particular genes involved in signal transduction pathways and cancer. This led to deep insights into RAS function, eventually solving the RAS biochemical pathway in yeasts and humans (96), and demonstrating the multifunctional nature of this important oncogene (106).

In the early 90’s, Wigler and collaborator Clark Still at Columbia University developed the first method for encoded combinatorial chemical synthesis, a method for building vast libraries of chemical compounds (99). This approach is still used today for drug discovery.

During the same period, Wigler and Nikolai Lisitsyn developed the concept and applications of representational genomic analysis (95), which led to the identification of new cancer genes, including the tumor suppressor PTEN (117), and viruses. In the late 90’s, Drs. Wigler and Robert Lucito and combined genome representations with array hybridization leading to a technique called ROMA (126, 134) used to detect copy number variation and with minor changes to perform genetic typing.

In the current decade, Wigler and Jim Hicks of Cold Spring Harbor, and Anders Zetterberg of the Karolinska Institute, applied ROMA to the analysis of breast cancer (145), which will perhaps lead to useful tests directing cancer treatment. At the same time, Drs. Wigler, Jonathan Sebat and Lakshmi Muthuswamy began copy number analysis of healthy individuals, leading to the discovery of a new source of genetic variability, copy number variation or CNVs (137). The abundance of CNVs in the human genome is strong evidence for our continuing evolution and a major source of individual variation.

The team led by Wigler at CSHL then continued this line of work to demonstrate that spontaneous germ-line mutation is likely to be a common cause for autism (147). Their observations and theories about autism provide an alternative approach and explanation for understanding other human mental and physical abnormalities (148).

For his contributions to biomedical research, Wigler is a recipient of numerous awards and honors and is a member of the National Academy of Science (since 1989), the American Academy of Arts and Sciences (since 1998), and is American Cancer Society Lifetime Research Professorship (since 1986).

References

1. ^ Wigler, M.H., Silverstein, S., Lee, L.S., Pellicer, A., Cheng, Y. and Axel, R. (1977)

• Wigler, M.H. and Weinstein, I.B. (1975). "A preparative method for obtaining enucleated mammalian cells", Biochemical and Biophysical Research Commun. 63 : 669-674.
• Wigler, M.H., Ford, J.P. and Weinstein, I.B. (1975). "Glucocorticoid inhibition of fibrinolytic activity production by tumor cells.", Cold Spring Harbor Symp. on Proteases and Biological Control, 849-856.
• Wigler, M.H. and Weinstein, I.B. (1976). "A tumor promoter induces plasminogen activator.", Nature 259: 232-233.
• Wigler, M.H. and Axel, R. (1976). "Nucleosomes in metaphase chromosomes.", Nucleic Acids Res. 3: 1463-1472.
• 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.

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Name	Wigler, Michael
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Date of birth	September 3, 1947
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