Geoffrey M. Wahl
Gene Expression Laboratory
Daniel and Martina Lewis Chair
Geoffrey M. Wahl, a professor in the Gene Expression Laboratory, is studying the genetic basis of the origin and progression of cancer and why tumors become resistant to drugs.
Wahl has been involved in various aspects of cancer research for his entire 40 year career, first as a graduate student of Dr. Mario Capecchi, then as a post-doctoral fellow with Dr. George Stark. Since that time, Wahl's own lab has focused on identifying the molecules and mechanisms involved in the genetic and phenotypic heterogeneity common to most human cancers. Their work has involved uncovering the mechanisms that lead to the most common forms of genetic instability in human cancers. This led them to investigate the mechanisms that prevent normal cells from acquiring the large-scale chromosomal changes that fuel the progression of many cancers. This work revealed that one function of the p53 tumor suppressor, one of the most commonly mutated genes in human cancer, is to prevent the emergence and proliferation of cells with genome instability. However, Wahl and his colleagues have also recognized that in some cancers, such as pancreatic cancer, there is substantial proliferation of an abnormal stroma that augments the growth of the associated epithelial cancer cells, and that this stroma has normal p53 that can be activated. They are currently working on strategies to activate the p53 in the abnormal stroma to see whether this also impedes growth of co-cultured pancreatic cancer cells or decreases the stromal response in vivo. More recently, they showed that p53 can also limit the ability of normal cells to de-differentiate into pluripotent stem cells, and that its mutation in cancer correlates with the acquisition of a de-differentiated stem-like state associated with some of the most aggressive forms of breast cancer. Most recently, they have become interested in the nature of the stem-like cells in a dangerous form of very aggressive breast cancers referred to as "triple negative" because they lack or have low expression of estrogen and progesterone receptors and the Her2 protein, which encodes an epidermal growth factor related receptor. The Wahl lab has also identified, isolated and characterized the stem cells that are formed in the fetus. The genes expressed in these fetal mammary stem cells show significant similarities to those expressed in the triple negative breast cancers. They are now characterizing these cells further in an attempt to identify molecular targets for which non-genotoxic therapeutics can be developed to provide an alternative, or addition, to the chemotherapy currently used to treat patients whose cancers show an enrichment for the fetal mammary stem cell signature.
- BA, Bacteriology, UCLA
- PhD, Biological Chemistry, Harvard University
- Postdoctoral fellow, Stanford University
Awards and Honors
- National Institutes of Health Postdoctoral Fellowship
- American Cancer Society Senior Fellowship
- American Men and Women of Science
- "Citation Classic" Designation for one of the most highly cited scientific papers, 1961-1982