Professor, Cancer Genetics
Cold Spring Harbor Laboratory
Cold Spring Harbor, New York
Seeking to characterize the interaction between normal (host) cells and tumor cells that will inform new strategies to prevent or treat breast cancer.
Sophisticated cell sorting and DNA sequencing technologies are employed to understand how non-tumor cells in the tumor environment influence tumor behavior.
These studies will help direct new drug development for the prevention and treatment of breast cancer.
Tumors cells interact with non-cancerous cells in the patient (“the host”) that influence the response to treatment and tumor behavior. With technology developed by Dr. Wigler in collaboration with BCRF colleague James Hicks, researchers can now study breast cancer at the single-cell level, setting the stage for the development of new diagnostic tools that will aid in therapeutic management of the disease.
Since developing the first single-cell genomic methods in 2011, Dr. Wigler has focused his BCRF research on the dual goals of improving the technology and applying it to take breast cancer therapy to a new level of precision and effectiveness.
In the coming year, he will decipher the interactions between cancer cells and the host microenvironment to better understand how this interplay influences tumor cell death, survival and response to treatment. Dr. Wigler believes that these studies will demonstrate that the tumor microenvironment both fights and assists the cancer in its growth and spread.
To achieve this, Dr. Wigler's team established a collection of frozen surgical samples and use extremely powerful molecular and computational techniques to explore both the types of host cells that surround the cancer, and ways the host and cancer cells influence each other.
Identifying the types and functional states of cells in small “neighborhoods” around the tumor is one way to understand the complex interactions between the host and the cancer, to identify those that improve or worsen outcome, and eventually to intervene to achieve a positive outcome for the patient. This information will help direct the development of new generations of targeted therapies.
Cold Spring Harbor Laboratory scientist Michael Wigler, PhD, in collaboration with James Hicks, PhD, is analyzing the genomes of women with breast cancer in research aimed at eliminating "trial-and-error" approaches to therapy. This work is leading to diagnostic tests capable of distinguishing cancers likely to spread and should receive aggressive treatment from those that are benign and can be left untreated. In this effort, Drs. Wigler and Hicks are using powerful technologies that they developed to analyze genomic and epigenetic changes in thousands of breast cancers and have identified three distinct categories of breast cancer DNA profiles associated with different outcomes for patients. Their research has provided important information about which patients are most likely to benefit from treatment with specific drugs, such as taxol and Herceptin®. Drs. Wigler and Hicks have also developed a sensitive technology called single nucleus sequencing (SNS) that can identify genetic changes in very small samples, which can be used to follow genetic changes as tumors progress and to identify specific changes that can predict which tumors are likely to metastasize. The group is continuing to make technological improvements to make it affordable and feasible for SNS to be used as a monitoring tool for early detection of cancer cells in the blood, and to direct therapy based on the genetic makeup of those circulating cancer cells.