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.
Portrait of a Neuroscience Powerhouse
April 27, 2018
A relatively small neuroscience group at CSHL is having an outsized impact on a dynamic and highly competitive field
Autism genetics study calls attention to impaired motor skills, general cognitive impairment
February 7, 2018
New research on the genetic causes of autism calls attention to diminished motor skills and suggests the importance of broad cognitive impairment
New method to determine before surgery which prostate tumors pose a lethal threat
December 1, 2017
The news about prostate cancer can be confusing. It’s the third most common cancer type among Americans.
Next-gen cancer test
November 24, 2017
Knowing that cancers become lethal when they spread, investigators at Cold Spring Harbor Laboratory seek a way of detecting tumors much earlier
New statistical method finds shared ancestral gene variants involved in autism’s cause
June 21, 2017
Researchers find children with autism are genetically more like other autistic children than their unaffected siblings.
Why is autism more common in boys?
April 29, 2016
Ivan Iossifov talks about some of the reasons why autism disproportionately effects boys on a genetic level.
Where does autism come from when it doesn’t run in the family?
April 7, 2016
Associate Professor Ivan Iossifov discusses how parents who are not autistic can pass autism onto their children through their genes.
Finding huge promise in a single cell with student Robert Aboukhalil
November 2, 2015
Robert Aboukhalil use his skills as a computational biologist to make single-cell genomic data easy for scientists and clinicians to access and use.
Breaking down breast cancer at CSHL
October 30, 2015
A look at how several researchers at CSHL contribute to the field of breast cancer research.
Genetic analysis supports prediction that spontaneous rare mutations cause half of autism
September 22, 2015
Scientists find evidence suggesting that devastating “ultra-rare” mutations play a causal role in roughly half of all autism spectrum 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.
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