Geoffrey M. Wahl, PhD
La Jolla, California
Daniel and Martina Lewis Chair, Gene Expression Laboratory
Salk Institute for Biological Studies
La Jolla, California
Advancing the understanding of how obesity contributes to breast cancer.
Breast cancers start with mutations in key genes that turn normal cells into cells that divide uncontrollably. However, cells can have cancer-causing mutations, yet not turn cancerous. Other factors must come into play to cause cells to become cancerous. Dr. Wahl is studying how obesity, a major breast cancer risk factor, and menopause alter mammary cells and those that surround them to initiate cancer. Insights gained from his work may lead to new strategies to stop cancer progression.
Progress Thus Far
Dr. Wahl and his team discovered that obesity and changes associated with menopause alter some types of breast cells and cause them to become more plastic, or able to shift to a cancer stem cell-like state. They speculate that this plasticity, in combination with the right genetic mutations, might increase the chances of the altered cells turning cancerous.
During the coming year, Dr. Wahl and his team will use new breast cancer models and powerful molecular technologies and information technology to determine how obesity, combined with the post-menopausal environment, lead to cancer initiation and progression. They will use cells with a well-known BRCA1 mutation and a mutation in p53—tumor suppressor genes frequently mutated in the most aggressive breast cancers—for their studies. Dr. Wahl anticipates that this work will reveal how these factors change the breast cells and the cells they interact with to initiate aggressive breast cancers.
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.
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