Michael Wigler

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.