Titles and Affiliations

Senior Research Scientist
Van Andel Research Institute
Grand Rapids, Michigan

Research area

Understanding how tumors spread to other tissues and identifying 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 treat it. The research team of Drs. Graveel 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 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.

Progress Thus Far

Drs. Graveel and Tsarfaty found that by activating distinct signals, MET promotes motility of breast tumor cells and in turn, metastasis. The team has also identified several mechanisms by which MET can drive metabolic reprogramming in tumors. In addition, they are using novel laboratory models of breast cancers with activated MET and p53 and BRCA1—other cancer-promoting genes—to identify “modifier genes” that influence breast cancer risk and prognosis. To understand which breast cancer patients will benefit from therapeutically targeting MET, the team tested MET inhibitors in breast cancer models, revealing prognostic indicators for tumors that are sensitive or resistant to MET inhibition. Lastly, they discovered that the tumor suppressor gene NF1 is altered in 25 percent of human breast cancers and may be an important genetic driver of breast cancer initiation and hormone resistance.

What’s next

In the upcoming year, Drs. Graveel and Tsarfaty will continue their work to understand MET-induced cell motility in cancer progression. The team will also continue to identify and validate “modifier genes” of MET, p53, and BRCA1 that induce breast cancer. Lastly, they will study the role of NF1 deficiency in promoting estrogen receptor-positive breast cancer.

Biography

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.

BCRF Investigator Since

2014

Co-Investigator