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Using Single-Cell Profiling to Uncover Vulnerabilities in Breast Cancer

Tuesday, December 21, 2021
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The UMass Cancer Center Pilot Grant Program fosters exciting science and innovation in cancer research at UMass Chan Medical School. The goal of the program is to provide support for cancer discoveries at their earliest phase, and facilitate further development of projects to a stage when they can obtain external support.

In its inaugural year, The UMass Cancer Center Pilot Grant Program awarded funds for three projects. One of the awards went to Thomas G. Fazzio, PhD, professor of molecular, cell & cancer biology for his project entitled "Using single-cell chromatin profiling to uncover epigenetic vulnerabilities of triple-negative breast cancer". Theproject aims to tackle the question of how subpopulations of cells within a breast tumor turn on certain genes that can, for example, make them more malignant and more resistant to chemotherapies. The malignant cells that still survive after chemotherapy can regenerate the tumor, leading to relapse of cancer.

Dr. Fazzio’s research centers on understanding the basic mechanisms of how different cells in the body turn certain genes on and off—the sum total of which is referred to as a cell’s “gene expression pattern”—to give them their unique properties, and how disruption of those processes can lead to disease, including cancer. In his pilot project, Dr. Fazzio will apply what he’s learned in studying these basic gene expression mechanisms to investigate how malignant cells in a tumor turn on their own unique subset of genes, which gives them their properties of malignancy and drug resistance.

Because different cells turn on different genes in a tumor, researchers need to look cell-by-cell to study how factors turn on genes in one cell and a different subset of genes in a different cell. To do this, Dr. Fazzio will use a method recently developed in his lab (called "multi-CUT&Tag"), which looks at factors that turn genes on and off in single cells, to understand how gene expression patterns emerge in malignant cells. The results from his study may lead to the development of new directed therapies for metastatic breast cancer. Dr. Fazzio notes, "We think this is important because if we understand how these different gene expression patterns are made in these tumor cell populations, we think that we can then target the factors that regulate the genes, and this may be more effective than targeting the genes that are on and off themselves."

Watch Dr. Fazzio’s discussion of the funded pilot project below.

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