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Carrie R. Graveel, PhD
Research Assistant Professor
Van Andel Research Institute
Grand Rapids, Michigan
Goal: To identify novel targets for the treatment of metastatic breast cancer.
Impact: Drs. Graveel, Vande Woude, and Tsarfaty are investigating how a gene called MET promotes the spread of breast cancer (metastasis) and resistance to therapy in patients with aggressive breast cancers. They hope to identify biomarkers of response to therapy and identify new approaches for preventing metastasis.
What’s next: The team will continue to pursue genes that play a role in breast cancer risk and treatment resistance.
In order for breast cancer to spread to other locations in the body, cancer cells must break away from the primary tumor and travel through the blood or lymph system before invading distant tissues. Oncogenes are genes with potent tumor promoting effects. Drs. Graveel, Vande Woude, and Tsarfaty are studying the oncogene MET which promotes metastasis and resistance to treatment. They are using laboratory models to investigate how MET drives these activities in aggressive forms of breast cancer.
Full Research Summary
Research area: To understand how tumors spread to other tissues and identify new targets for therapeutic development.
Impact: Breast cancers that spread to other tissues—a process called metastasis—have evolved to gain a survival advantage that makes them resistant to cancer therapies. There is no cure for metastatic breast cancer and an urgent need to find effective therapies to both prevent breast cancer from spreading and treating it in those diagnosed with metastatic breast cancer. The research team of Drs. Graveel, Vande Woude, and Tsarfaty have been studying a potent driver of metastasis called MET. With BCRF support, their work has led to new insights into the activity of MET in promoting the motility and survival of cancer cells and identified other genes that partner with MET in its metastatic program. Collectively, their work is increasing our understanding of how cancer cells gain the ability to spread and form new tumors and will inform new strategies to treat and prevent metastatic breast cancer.
Current research: The research team will continue ongoing studies using specially designed laboratory models to delineate the role of MET in breast cancer metastasis.
What they’ve learned so far: In the last year, the team identified several genes that modify the ability of MET to promote breast cancer initiation and progression; defined several metastasis-promoting programs activated by MET; and discovered that MET expression is found at high levels in some tumors from patients with estrogen receptor-positive and triple-negative breast cancers.
What’s next: Using their unique laboratory models and expertise they will identify and characterize the modifier genes that promote MET-mediated tumorigenicity. The relevance of these modifier genes will be examined in human breast cancers. They will further interrogate the role of MET inhibitors in aggressive breast cancer. Overall, these studies will provide an unprecedented view of the genes that influence breast cancer tumor initiation and progression and identify potential prognostic signatures and therapeutic targets.
Dr. Carrie R. Graveel earned her PhD. in Cellular and Molecular Biology from the University of Wisconsin-Madison in 2002. She then served as a postdoctoral fellow in the laboratory of Dr. George Vande Woude at Van Andel Research Institute (VARI) from 2002-2007. In 2007, Dr. Graveel became a Research Scientist and in 2010 was promoted to Senior Research Scientist. In 2011, Dr. Graveel became an Instructor in the VAI Graduate School and in 2013 was named a Research Assistant Professor in VARI. Dr. Graveel’s work was the first to determine that a mutationally activated receptor tyrosine kinase (MET) can induce diverse tumors in vivo. In 2009, she was the first to demonstrate that the MET oncogene plays a critical role in triple-negative breast cancer and may be an attractive target for clinical treatment. Recently, her laboratory demonstrated that MET may play a role in therapeutic resistance of HER2+ breast cancers. Currently, her work focuses on how receptor tyrosine kinase signaling networks drive tumor progression and can be leveraged to develop effective therapeutic strategies for triple-negative breast cancer patients.