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Michael H. Wigler, PhD
Professor, Cancer Genetics
Cold Spring Harbor Laboratory
Cold Spring Harbor, New York
Goal: To understand the interaction between normal (host) cells and tumor cells that will inform new strategies to prevent or treat breast cancer.
Impact: Dr. Wigler and his team have developed powerful methods that will help them see characteristics of individual cells and how they interact with neighboring cells. These tools can be implemented to assess tumor response to treatment.
What’s next: Using these methods, Dr. Wigler will study certain types of host cells that accompany cancer when it spreads to other locations in the body.
The environment that surrounds a tumor is composed of non-cancer cells and host factors—factors unique to each patient—that interact with tumor cells. These interactions influence the growth of the tumor as well as its response to therapy. Dr. Wigler is conducting studies to identify the types and functional states of individual cells and cells in the “neighborhoods” around the tumor that could lead to new drug development for the prevention and treatment of breast cancer.
Full Research Summary
Research area: Finding and characterizing the cells of breast cancer patients that both fight and assist the cancer in its growth and spread.
Impact: Tumor cells interact with non-cancer cells and host factors, and this microenvironment influences tumor growth and its response to anti-cancer therapies. Dr. Wigler’s investigations of the host elements associated with tumor growth, response to therapy, and relapse could inform new generations of targeted therapies.
Current investigation: Dr. Wigler is focused on improving the technology and application of single-cell genomic methods, which allows researchers to study breast cancer at the single-cell level. He developed the first of these methods in 2011 with BCRF colleague James Hicks, PhD.
What he’s learned so far: He and his team recently developed powerful new tools for single-cell and nuclear RNA and DNA sequencing. His team implemented informatics for identifying both tumor and normal cells from the patient's tumor biopsy and blood.
What’s next: Dr. Wigler will use his single-cell sequencing method to begin to characterize tumor response to treatment. In the upcoming year, he hopes to put the tools in place so that his laboratory can routinely profile DNA and RNA content of the cells at a tumor site, thus identifying the physiological state of tumor and host cells. Once these tools are in place and are shown to be reliable, Dr. Wigler and his team can begin the process of cataloging the cell types and states in order to make predictions about outcome and recommendations for treatment.
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.