Daniel and Martina Lewis Chair, Gene Expression Laboratory
The Salk Institute
La Jolla, CA
Dr. Wahl’s BCRF research is focused on understanding the properties of stem-like cells in triple negative breast cancer, a very aggressive type of breast cancer that is so named because the tumor cells lack the estrogen and progesterone receptors and the Her2 protein. Stem cells are the cells from which tissues are derived during development. They are also believed to be the cells that give rise to tumors and promote tumor progression. Work in Dr. Wahl’s group showed that genes expressed in mammary stem cells (MaSCs) show significant similarities to those expressed in triple negative breast cancers. They are now characterizing these cells further in an attempt to identify molecular targets for the development of new therapeutics that can provide an alternative to, or be used in combination with, chemotherapy in patients whose cancers show a mammary stem cell signature. One such factor is called fibroblast growth factor (FGF). Dr. Wahl’s laboratory discovered that FGF affects the production of the SOX10 protein, an important regulator of stem cell development. They recently identified novel gene combinations in mammary stem cells and are now using sophisticated genetic engineering strategies to generate a laboratory model of breast cancer to test the idea that a multi-gene profile identified a cell as being in a stem cell state. Additionally, they are working to identify proteins in mammary stem cells and human breast cancers that may lead to the development of tests to detect basal-like TNBC earlier and devise new immunotherapeutic approaches.
Dr. Geoffrey M. Wahl is a Professor at the Salk Institute, an Adjunct Professor at the University of California, San Diego in the Department of Biology, and the past President of the American Association for Cancer Research (2006-2007). Dr. Wahl’s research focuses on the cells that originate and perpetuate cancers, the conditions that lead to cancer progression and metastasis, and why tumors become therapy resistant. Dr. Wahl’s early work involved uncovering the mechanisms that lead to the most common forms of genetic instability in human cancers, including those often seen in the highly aggressive, basal-like group of triple negative breast cancers. BCRF funds have been used to discern the nature of the cells that originate or perpetuate basal-like breast cancers. The Wahl laboratory found that mutations in the p53 gene, the most commonly mutated gene in basal-like breast cancer, increases the chances that a fully mature cell can "reprogram" into a more primitive "stem-like" cell. His lab also found that these primitive cells have strong similarities to the earliest stem cells identifiable during breast development, which they call fetal mammary stem cells. BCRF funding is enabling Dr. Wahl’s team to characterize the pathways essential for the growth and survival of these cells, as he expects these pathways will be important for perpetuation of basal-like breast cancers. The Wahl lab is also identifying molecules useful for tracking these cells in the body. Their hope is that these approaches will lead to development of new molecularly targeted therapeutics and diagnostic tools to provide alternatives, or additions, to chemotherapy, currently the only type of drug therapy for patients with triple negative breast cancer.