Professor, Gene Expression Laboratory
The Salk Institute
La Jolla, CA
Dr. Wahl's group recently reported the first identification, isolation, and characterization of cells that arise during formation that give rise to the entire mammary gland later in life. They call these cells fetal mammary stem cells (fMaSCs). Over the past six months, they improved on their ability to grow fMaSCs in the laboratory. This is a big step forward to enable investigators to study the pathways that control their growth, and how these pathways contribute to specialized stem cell functions such as self-renewal (immortality). This has relevance for human breast cancer since Dr. Wahl and colleagues found that certain pathways that the fMaSCs use are very similar to those in a significant subset of triple negative breast cancers. They also made considerable progress devising simpler and faster methods to obtain more pure fMaSCs. They are now developing state of the art techniques to engineer fMaSCs to contain “molecular light switches” that will enable them to locate fMaSCs in the developing mammary gland, and to determine how fMaScs contribute to laboratory and human breast cancer.
BCRF support has enabled Dr Wahl and his team to identify, isolate, and characterize the very earliest stem cells that contribute to the formation of the mature breast. They did these studies in laboratory models, as they would not be possible in humans. They hypothesized that there would be many similarities between these stem cells and the cancer cells found in some of the most dangerous human cancers, which pathologists often refer to as “undifferentiated”, a term also used to describe stem cells. To extend these studies, Dr. Wahl’s team needed to determine how to grow the early stem cells in the laboratory, and they have over the past six months made considerable progress towards this goal. They also needed to determine all the genes that the stem cells express. They have now used the most cutting edge molecular technology to make significant progress towards this considerable challenge. This will be a significant advance for fields spanning breast development and breast cancer.
Dr. Geoffrey M. Wahl is a Professor in the Gene Expression Laboratory at the Salk Institute in La Jolla, CA and an Adjunct Professor at University of California, San Diego. He received his bachelor’s degree in Bacteriology at UCLA and his doctorate from Harvard. Dr. Wahl pursued post-doctoral studies at Stanford. Dr. Wahl's lab studies two cancer-related topics. First, he is determining how p53, the “Guardian of the Genome” works to prevent tumors from forming. 50% of breast cancers have mutationally inactivated p53, and the others have normal p53 that has lost its ability to work. An important goal is to activate this “latent p53” in these cancers, which should restore its ability to induce the cell death or arrest programs it normally uses to suppress tumor formation. This would provide a new form of individualized cancer therapy. Second, he is identifying, isolating and characterizing the stem cells that generate the mammary gland to determine whether these cells, or cells that behave like them, contribute to breast cancer.. His group recently found that these developing mammary stem cells share similarities with some types of breast cancer in specific patients.