University of California San Francisco, California
Professor and Director Center for Bioengineering and Tissue Engineering
Identifying and targeting drivers of drug resistance, recurrence, and metastasis in aggressive breast cancer.
HER2-positive and triple-negative breast cancers are aggressive and often spread to other parts of the body. Many patients’ cancers will still progress after intensive treatment, including immunotherapy. The discovery of the protein NCOR2 as a driver of poor prognosis and metastasis has opened new directions for investigating targeted therapies. By understanding how NCOR2 enables tumors to survive, resist treatment, and evade the immune system, Dr. Weaver and her team aim to develop therapies that target NCOR2 activity and expression to improve survival outcomes.
Dr. Weaver’s team have found that tumors containing high levels of NCOR2 make breast cancers resistant to therapy and impair the body’s ability to mount an immune response. Their data demonstrate that NCOR2 promotes metastasis by protecting tumor cells from destruction. They also discovered that the most aggressive breast tumors are physically stiffer, and that stiffness correlates with high NCOR2 and metastasis. Women with BRCA1 mutations were found to have stiffer breast tissue and higher NCOR2 expression, suggesting a biological link between genetic risk and tumor aggressiveness.
Dr. Weaver and her team will examine how breast stiffness increases NCOR2, focusing on the Notch signaling pathway, which is linked to cancer occurrence and progression. They will expand studies to better understand NCOR2’s role in brain metastasis, and studies will continue on the relationship between stiff breast tissue and elevated NCOR2 levels in women with BRCA1 mutations and breast cancer development. These studies will provide proof-of-concept for targeting NCOR2 in clinical trials for patients with HER2-positive and triple-negative breast cancers. Long term, the findings may also guide strategies to prevent breast cancer in high-risk women, including those with inherited BRCA1 mutations.
Dr. Weaver is currently the Director of the Center for Bioengineering and Tissue Regeneration in the Department of Surgery, and is a Professor in the Departments of Surgery, Radiation Oncology and Bioengineering and Therapeutic Sciences at UCSF in San Francisco, CA.
Dr. Weaver has over 20 years of experience in leading interdisciplinary research in oncology, including leadership of significant program projects including the Bay Area Physical Sciences and Oncology program and the UCSF Tumor Microenvironment Brain Program that merge approaches in the physical/engineering sciences with cancer cell biology and emphasize the role of the tumor microenvironment. Her research program focuses on the contribution of force, cell-intrinsic as well as extracellular matrix, to breast, pancreatic, and glioblastoma tumor development and treatment. She also has an active research program exploring the interplay between cell and tissue level force and human embryonic stem cell differentiation.
Her education took place in Canada, with a bachelor’s degree in Chemistry from the University of Waterloo, an Honors Bachelor’s and PhD degree in Biochemistry from the University of Ottawa with a two-year postdoctoral training at the Institute for Biological Sciences, National Research Council of Canada and a 5-year postdoctoral tenure in Cancer Cell Biology at the Lawrence Berkeley National Laboratory at UC Berkeley with Dr. Mina J Bissell.
Dr. Weaver was recruited to the University of Pennsylvania in Philadelphia where she joined the faculty in the Department of Pathology as an Assistant Professor and was appointed a full member of the Institute for Medicine and Engineering. In mid-2006 she relocated to UCSF in San Francisco as an Associate Professor in the Department of Surgery with a joint appointment in Anatomy to take on the Directorship of the Center for Bioengineering & Tissue regeneration. She was invited to join the UCSF Cancer Center and Stem Cell Programs in 2007 and was cross appointed to the newly formed Department of Bioengineering and Therapeutic Sciences in 2008 and was promoted to full Professor in 2010.
Dr. Weaver has been recognized for her research and leadership through receipt of several awards including the DOD BCRP Scholar award in 2005 and the DOD BCRP Scholar expansion award in 20013 for exceptional creativity in breast cancer research and the ASCB WICB Midcareer award for sustained excellence in cell biology research in 2014. Most recently she was elected as the chair of the AACR TMEN working group in 2015 and she was elected to be a fellow of the American Society for Cell Biology in 2017.
2018
The Women's Cancer Research Fund Award
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