Michael Wigler, PhD

2012-2013 BCRF Project:
(made possible with generous support from Play for P.I.N.K.)
Co-Investigator: James Hicks, PhD, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York

Drs. Wigler and Hicks are paving a technological path that has many potential applications in the clinical setting. Major progress has been made to determine epicenters of genome instability in breast cancer. They have correlated genome instability with prognosis, developed improved alternatives to fluorescent-in-situ-hybridization for the determination of important pathology-related parameters, and begun to understand the growth and evolution of breast tumors through their breakthrough research on the genomic analysis of individual cancer cells from tumors and metastases. Their work in 2012-2013 will extend their research further into understanding how cancer cells change, grow, and migrate through the body. It will also enhance current knowledge on which cells need to be killed to prevent metastasis. The goal of Drs. Wigler and Hicks's research builds on advances in technology, data interpretation, and gene discovery and applies them towards the benefit of patients.

Mid-year Progress: Drs. Wigler and Hicks are applying genetic tools that they developed to follow the initiation and progression of breast cancer at the level of the single cancer cell. Their methods take advantage of the latest DNA sequencing technologies and computer driven analysis to derive the genetic "fingerprints" that distinguish cancer cells from normal cells in the body and provide a unique picture of each individual cancer. This work has many potential applications in the clinical setting but still requires additional advances in technology and data interpretation before its true benefits to the patient can be realized. Great strides have been made toward realizing an improved version of the single cell methodology that will vastly increase efficiency and reduce the costs for each cell by tenfold. This breakthrough will be further optimized in the coming months, with the goal of making it routine for the general medical community. Significant progress was also made in Drs. Wigler and Hicks's ongoing efforts to use single cell genomics to determine which cancer cells migrate in the body to cause metastasis and to explore the nature of those metastatic cells by tracing the lineages of hundreds of cancer cells between primary and metastatic sites. The team will now focus on further optimizing single cell analysis so it can be accomplished more quickly, and at lower cost. These methods will extend the reach of the single cell technology into a greater understanding of how cancer cells change, grow and migrate through the body to seed life threatening metastases and further, which cells need to be killed to prevent metastasis.

Bio:
Dr. Wigler grew up in Garden City, on Long Island, New York. He attended Princeton University as an undergraduate, and Columbia University for graduate studies. After graduate school, he commenced his independent scientific studies at Cold Spring Harbor Laboratory, where he continues his work to this day. He is a recipient of numerous awards and honors, and is a member of the National Academy of Science, the American Academy of Arts and Sciences.

While Dr. Wigler was a graduate student, he developed effective and flexible methods for engineering animal cells, a method that is the basis for the production of medicinally useful proteins even today. After moving to Cold Spring Harbor Laboratory, Dr. Wigler continued his studies of gene transfer, exploring the integration of foreign DNA and the stability of gene expression in transfected cells, demonstrating the inheritance of DNA methylation patterns, and isolating the first mammalian genes, such as the ras oncogenes, 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. Subsequently, Dr. Wigler used yeast as model genetic systems for the study of signal transduction pathways and oncogenes, culminating in the elucidation of the ras oncogene pathway in yeasts and humans.

In the early nineties, Dr. Wigler and collaborators developed the first method for encoded combinatorial chemical synthesis, a method that is used today for drug discovery, and developed a powerful method for DNA difference analysis called RDA. This method has led to the identification of many new oncogenes, tumor suppressors and pathogens.

Dr. Wigler continues to work in the area of cancer and human genetic disease, and most recently has developed microarray based hybridization methods for comparing the genomes of diseased and healthy cells.