Cold Spring Harbor Laboratory
Cold Spring Harbor, New York
Professor, Cancer Genetics
Understanding the interactions between normal cells and tumor cells to find new strategies to prevent or treat breast cancer.
Tumor cells interact with non-cancer cells and other tissue components that make up the tumor microenvironment, which influences tumor growth and its response to anti-cancer therapies. Dr. Wigler and his team have developed powerful tools to study characteristics of individual cells and how they interact with neighboring cells. They are developing these tools to characterize the heterogeneity of cancer and assess tumor response to treatment to ultimately personalize the prevention and treatment of breast cancer.
Dr. Wigler and his team analyzed the genome and protein expression status of thousands of single cells from five primary endometrial cancers. They determined the structural tissue components in each sample, which differed among patients but also among samples from the same patient. Dr. Wigler found that the cells of some structural components surrounding tumors have mutated genes—which could play a role in cancer progression. Indeed, immune cells may travel with cancer cells during the metastatic process. The team is developing further tools that will enable them to look more deeply into the structure of cancer and stromal cells and ultimately aim to characterize all the cell components in a surgical biopsy.
In the upcoming year, Dr. Wigler and his team will continue developing and applying tools for the single cell analysis of normal and cancer cells at the primary sites of breast cancer to find clues into the cancer’s history and its future trajectory in individual patients. They are developing a tool to visualize differences in cells by microscopy. The team aims to get a clearer picture of the heterogeneity of cancers and of the interaction between cancer and the normal cells.
Cold Spring Harbor Laboratory scientist Michael Wigler, PhD, in a prior collaboration with James Hicks, PhD, analyzed 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, the team developed and used powerful technologies 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®.
Dr. Wigler and his team have also developed a sensitive technology called single nucleus sequencing (SNS) that can identify genetic changes in very small samples and provide a method to follow genetic changes as tumors progress and identify specific changes that can predict which tumors are likely to metastasize. His group continues 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.
1998
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