Geoffrey M. Wahl, PhD
La Jolla, California
Daniel and Martina Lewis Chair, Gene Expression Laboratory
Advancing the understanding of how the environment surrounding breast cells 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.
Dr. Wahl and his team discovered that obesity and changes associated with menopause alter some types of breast cells and cause them to adapt and become more plastic, or cancer stem cell-like. Using breast cancer models and powerful computational techniques, they found genetic drivers of plasticity that, when combined with the right genetic mutations, can increase the chances of the altered cells turning cancerous.
During the coming year, Dr. Wahl and his team aim to determine when such changes occur by comparing clinical samples of non-invasive ductal carcinoma in situ (stage 0 breast cancer) and invasive breast cancer. Dr. Wahl’s goal is to understand enough about the molecular mechanisms underlying cellular adaptability to develop therapies that can disrupt the process.
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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