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Carrie R. Graveel, PhD
Senior Research Assistant Professor
Van Andel Research Institute
Grand Rapids, Michigan
Impact: Drs. Graveel, Tsarfaty, and Vande Woude are investigating how a gene called MET and partner oncogenes promote 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 a detailed understanding of 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, Tsarfaty, and Vande Woude are studying the oncogene MET which promotes metastasis and resistance to treatment. They are using laboratory models to investigate how MET and other oncogenes drive 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 and treating it. The research team of Drs. Graveel, Tsarfaty, and Vande Woude 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 to promote metastasis. 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 Investigation: The research team will continue ongoing studies using specially designed laboratory models to delineate the role of the oncogenes MET, p53, mutant BRCA1, and NF1 in breast cancer therapy resistance and metastasis.
What they’ve learned so far: In the last year, the team characterized a novel, MET-induced aggressive subgroup of triple-negative breast cancer cells; defined several mechanisms of MET-induced metabolic reprogramming; and identified several genes that modify the ability of MET to promote breast cancer initiation and progression.
What’s next: Using their unique laboratory models and expertise they will identify and characterize the molecular mechanisms of MET-induced plasticity of breast cancer cells, which enables metastasis. Additionally, they will interrogate the role of MET, p53, mutant BRCA1, and NF1 genes that drive breast cancer resistance and metastasis. 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.