Michael H. Wigler, PhD
Cold Spring Harbor, New York
Professor, Cancer Genetics
Cold Spring Harbor Laboratory
Cold Spring Harbor, New York
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, which can be implemented to assess tumor response to treatment and to develop new drugs for the prevention and treatment of breast cancer.
This year, Dr. Wigler focused on developing single-cell genome analysis of cancer cells. He and his team analyzed genome and protein expression status from 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 described a phenomenon called “mimicry” in which a small number of normal cells display the tumor gene expression pattern, and a small number of tumor cells display the expression pattern of normal cells. This discovery could indicate the existence of a cancer precursor cell and reveal details about the early steps of cancer development.
In the upcoming year, Dr. Wigler and his team will expand their single-cell studies of patients with endometrial cancer to include patients with ovarian cancer. They plan to analyze more cells from each sample to identify rare but important cell subpopulations as well as expand the range of tissues analyzed including normal tissue adjacent to the tumor, lymph nodes, and metastases. Dr. Wigler will expand these studies to breast cancer with the aim of discovering early cancer progenitors, normal cell mimicry by the tumor cells, and identification of normal cell components.
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.
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