C. Kent Osborne and Rachel Schiff Laboratory
Our laboratory is a team effort between C. Kent Osborne, M.D., a clinical scientist and cell biologist, and Rachel Schiff, Ph.D., a molecular biologist, and is one of several basic/translational research laboratories comprising the Smith Breast Center at Baylor College of Medicine and The Methodist Hospital in the Texas Medical Center in Houston, Texas.
Both Drs. Osborne and Schiff have faculty appointments in the Department of Medicine and in the Department of Molecular and Cellular Biology. Dr. Osborne is the director of both the Dan L. Duncan Cancer Center and the Smith Breast Center and he has more than 25 years of experience in translational and clinical research in breast cancer. Dr. Schiff is well-experienced in molecular and cellular biology of breast cancer and is an expert in exploiting breast cancer preclinical models towards the development of novel approaches of targeted therapies.
The lab’s research objective is to understand the molecular mechanisms by which breast cancers become resistant to endocrine therapy and then to develop new treatment strategies to block or overcome this resistance.
In this research, we combine molecular/genetic analyses with cell biology to answer important clinically relevant questions using cell culture and animal models that we developed two decades ago, along with newly developed ones. Major interests include the crosstalk that we and others have discovered between growth factor receptor and/or other cellular kinase signaling and estrogen receptor signaling pathways, and the role of ER coactivators and corepressors in the development of hormone therapy resistance.
We have shown that growth factor receptor signaling such as that initiated by tyrosine kinase receptors of the EGF family play an important role in hormone therapy resistance and that blockade of these pathways represents a new strategy to prevent it. The ER coactivator AIB1 (SRC3) which is often either amplified and/or overexpressed in breast cancer, and the ER corepressor protein FKHR that is often lost in breast cancer are modulated by growth factor signaling and we believe are key to the resistant phenotype.
We are working to:
- Determine the mechanisms by which receptor tyrosine and serine/ threonine kinases cause resistance to tamoxifen and other endocrine therapies
- Investigate whether therapies that target these pathways can overcome resistance
- Identify the role of AIB1 phosphorylation in ER function and hormone therapy resistance
- Determine if the ER corepressor FKHR functions as a tumor suppressor gene in breast center
- Define molecular profiles in human breast cancer specimens that predict selective hormone therapy resistance and, then, identify new therapeutic targets to reverse it
For more details, please see the research page.