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Carrie R. Graveel, PhD
Research Assistant Professor
Van Andel Research Institute
Grand Rapids, Michigan
- Seeking to develop novel strategies to reduce drug resistance and metastasis in aggressive breast cancers.
- Laboratory studies are conducted to test a new drug target for combination therapy in triple negative breast cancers.
- This research may identify predictive biomarkers of response to targeted therapies and novel new combination approaches to counter drug resistance and prevent metastasis.
In order for a tumor to grow and spread to other tissues, it must activate cellular programs to support growth as well as the ability of tumor cells to invade and become mobile. Oncogenes are genes that drive this kind of activity and cause a tumor cell to become malignant. The research team of Drs. Graveel, Tsarfaty, and Vande Woude are conducting studies focused on an oncogene called MET in advanced breast cancers.
Full Research Summary
For a tumor to spread (a process called metastasis), tumor cells must be able to break through tissue barriers, enter the circulation, and become established in a new site. To achieve these steps, a tumor cell must acquire unique physical and molecular properties. This often involves the activation of a gene that is normally not active in adult tissue. The MET gene is one example. MET gene expression changes the properties of cancer cells and allows them to spread more easily.
The research team of Drs. Graveel, Tsarfaty, and Vande Woude use a combination of novel imaging techniques and mathematical models to study how MET influences breast cancer metastasis, metabolism, and drug resistance in HER2+ and triple negative breast cancers. Their recent studies have identified potential combination approaches that could reduce drug resistance and prevent metastasis in these diseases.
In the coming year, the international research team will continue to leverage the unique models to identify and characterize the modifier genes that promote MET-mediated tumorigenicity and further explore the potential of MET inhibitors in aggressive breast cancers that are resistant to other therapies.
Overall, these studies will provide new insights into the genes that influence breast cancer initiation and progression and identify potential prognostic signatures in patients who are responsive to MET-targeted therapies, and lead to the development of novel combination therapies.
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.