Michael Wigler, PhD

2011-2012 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

The BCRF-supported team at Cold Spring Harbor is paving a technological path in breast cancer research that has many potential applications in the clinical setting and is poised to bring about advances in technology, data interpretation, and gene discovery that will benefit the patient. Major progress has been made towards determining the epicenters of genome instability in breast cancer, correlating genome instability with prognosis, developing improved alternatives to fluorescent-in-situ-hybridization for the determination of important pathology-related parameters, and understanding the growth and evolution of breast tumors through genomic analysis. In 2011-12, Drs. Wigler and Hicks plan to initiate the examination of changes in DNA at the individual cell level as markers to aid in the control and early detection of breast cancer.

Mid-year Progress: Drs. Wigler and Hicks aim to further extend our understanding of how cancer cells change, grow,and migrate through the body, as well as the knowledge of which tpes of cells need to be killed to prevent metastasis.

The drawback of the single cell analysis protocol these researchers reported in their recent Nature paper (Navin, et al. 2011) was the cost of the protocol. In order to realize the power of single cell profiling to understand the makeup of tumors and the manner in which tumors grow and progress to metastasis, profiling hundreds of cells at a time is necessary but it is a cost-prohibitive task in the first iteration of the technology. Drs. Wigler and Hicks have been able to integrate computational approaches along with other methods and thereby reduce the sequencing costs for a single cell from nearly $2,000 a year ago to less than $100.

The Cold Spring Harbor team has made progress towards their other goals, including dissection of the genetic relationships and evolutionary dynamics between primary tumors and their metastatic counterparts. The results differ from previously published work but answer important questions regarding the biology of metastasis. Also, the researchers have nearly completed designing software for a novel method of genotyping, which is an essential prerequisite to inferring tumor lineages from microsatellite instability. With these newly obtained tools, Drs. Wigler and Hicks anticipate further enhancement of their research.

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.