Ph.D., Columbia University, 1978
|Devastating diseases like cancer and autism can be caused by spontaneous changes to our DNA – mutations first appearing in the child, or in our tissues as we age. We are developing methods to discover these changes in individuals, tumors, and even single cells, to promote early detection and treatments|
Michael Wigler’s work provides a new paradigm for understanding and exploring human disease. The Wigler lab studies human cancer and the contribution of new mutation to genetic disorders. The cancer effort (with James Hicks, Alex Krasnitz, and Lloyd Trotman) focuses on breast and prostate cancers. It involves collaborative clinical studies to discover mutational patterns predicting treatment response and outcome and the development of diagnostics to detect cancer cells in bodily fluids such as blood and urine. The major tools are single-cell DNA and RNA analysis. The single-cell methods, which are in development, are also being applied to problems in neurobiology (with Josh Huang and Pavel Osten) to characterize neuronal subtypes, somatic mutation, and monoallelic expression. The Wigler lab’s genetic efforts are a collaboration with Ivan Iossifov and Dan Levy, and this team focuses on determining the role of new mutations in pediatric disorders. In a large-scale population sequencing project with W. Richard McCombie and the Genome Sequencing Center at Washington University in St. Louis, and supported by the Simons Foundation, the team has proven the contribution of this mechanism to autism. The work further suggests a relationship between the mutational targets in autism and the process of neuroplasticity that lies at the heart of learning. Smaller-scale population studies of congenital heart disease and pediatric cancer (collaborations with scientists at Columbia University and Memorial Sloan- Kettering Cancer Center, respectively) also point to new mutation as a causal factor in these disorders.
Iossifov, I. and O'Roak, B. J. and Sanders, S. J. and Ronemus, M. and Krumm, N. and Levy, D. and Stessman, H. A. and Witherspoon, K. T. and Vives, L. and Patterson, K. E. and Smith, J. D. and Paeper, B. and Nickerson, D. A. and Dea, J. and Dong, S. and Gonzalez, L. E. and Mandell, J. D. and Mane, S. M. and Murtha, M. T. and Sullivan, C. A. and Walker, M. F. and Waqar, Z. and Wei, L. and Willsey, A. J. and Yamrom, B. and Lee, Y. H. and Grabowska, E. and Dalkic, E. and Wang, Z. and Marks, S. and Andrews, P. and Leotta, A. and Kendall, J. and Hakker, I. and Rosenbaum, J. and Ma, B. and Rodgers, L. and Troge, J. and Narzisi, G. and Yoon, S. and Schatz, M. C. and Ye, K. and McCombie, W. R. and Shendure, J. and Eichler, E. E. and State, M. W. and Wigler, M. (2014) The contribution of de novo coding mutations to autism spectrum disorder. Nature 515(7526) pp. 216-221.
Levy, D. and Wigler, M. (2014) Facilitated sequence counting and assembly by template mutagenesis. Proceedings of the National Academy of Sciences of the United States of America 111(43) pp. E4632-E4637.
Narzisi, G. and O'Rawe, Jason and Iossifov, I. and Fang, Han and Lee, Y. H. and Wang, Zihua and Wu, Yiyang and Lyon, Gholson J. and Wigler, M. H. and Schatz, M. C. (2014) Accurate de novo and transmitted indel detection in exome-capture data using microassembly. Nature Methods 11(10) pp. 1033-1036.
Wigler, M. H. and Lucito, R. (2014) Use of representations of DNA for genetic analysis. United States Patent 8663917.
Sebat, J. and Lakshmi, B. and Malhotra, D. and Troge, J. E. and Lese-Martin, C. and Walsh, T. and Yamrom, B. and Yoon, S. and Krasnitz, A. and Kendall, J. T. and Leotta, A. and Pai, D. and Zhang, R. and Lee, Y. H. and Hicks, J. B. and Spence, S. J. and Lee, A. T. and Puura, K. and Lehtimaki, T. and Ledbetter, D. and Gregersen, P. K. and Bregman, J. and Sutcliffe, J. S. and Jobanputra, V. and Chung, W. and Warburton, D. and King, M. C. and Skuse, D. and Geschwind, D. H. and Gilliam, T. C. and Ye, K. and Wigler, M. H. (2007) Strong Association of De Novo Copy Number Mutations with Autism. Science 316(5823) pp. 445-449.
Wigler, M. H. and Weinstein, I. B. (1975) Preparative Method for Obtaining Enucleated Mammalian-Cells. Biochemical and Biophysical Research Communications 63(3) pp. 669-674.Additional materials of the author at
CSHL Institutional Repository
Clusters of cooperating tumor-suppressor genes are found in large regions deleted in common cancers
A striking link is found between the Fragile-X gene and mutations that cause autism
Autism study validates importance of spontaneous causal mutations and sheds new light on gender skew
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