University of California San Francisco, California
Professor & Director, Center for Bioengineering and Tissue Regeneration
Identifying and targeting drivers of drug resistance, recurrence, and metastasis in breast cancer.
Triple-negative breast cancers (TNBCs) show a high propensity for metastasis, and patients with metastatic disease succumb to their cancer when their tumors don’t respond to therapy. This is particularly true for patients with brain metastasis. Newer immunotherapies are successful in some TNBC patients, but many do not benefit. Dr. Weaver and her team are studying the role of NCoR2 in drug resistance and metastasis in TNBC. NCoR2 is a protein involved in the regulation of the immune response and Dr. Weaver is working to uncover how it works to mask metastatic tumor cells from the immune system. She and her team are developing therapies to target NCoR2 activity and expression.
Dr. Weaver’s team initially found that tumors containing NCoR2 have worse prognosis, and NCoR2 levels are elevated in TNBC that metastasize to the brain. They discovered that breast tumors with high NCoR2 are very resistant to chemo- and radiotherapy because they repress a healthy T cell-mediated immune response, which helps them evade the immune system and metastasize. Using a novel gene therapy approach, they overcame NCoR2’s immune repression to boost chemotherapy and immunotherapy treatments in laboratory models. The team also determined that chemotherapy and the dense connective tissue that develops in TNBC and HER2-positive breast cancers induce the expression of NCoR2. Finally, the team determined the mechanism by which NCoR2 regulates metastatic outgrowth of breast cancer.
Dr. Weaver and her team will continue to examine how NCoR2 promotes brain metastasis and how NCoR2 modulates the immune response. The team is also exploring factors that induce NCoR2 activity, including tissue fibrosis and chemotherapy, to identify additional therapeutic targets. The work will serve as a proof of concept prior to clinical studies of new therapies targeting NCoR2 to improve outcomes in women with HER2-positive and TNBC.
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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