Geoffrey M. Wahl, PhD

2009-2010 BCRF Project:
The goals of this project are to identify and characterize mammary stem cells (MSCs), and to determine whether they contribute to mammary cancer. Dr. Wahl's laboratory made substantial progress over the past year in their overall objective of identifying, isolating, and characterizing the stem cells that generate the mammary gland. They narrowed down the time during development when these heretofore elusive cells are actually generated, and showed they are more easily identified in the embryo than in the adult. They then used special properties of the cell surface of mammary stem cells to isolate them in higher purity than achieved previously, and made significant progress in determining the genes they express that contribute to their ability to serve as stem cells.

Bio:
Dr. Wahl is a Professor in the Gene Expression Laboratory at the Salk Institute. His research concerns the cellular and genetic bases of the origin and progression of cancer and the development by tumors of resistance to drugs.

Dr. Wahl graduated Magna Cum Laude from the University of California, Los Angeles in 1970 with a B.A. in Bacteriology. In 1975 he received a PhD in Biological Chemistry from Harvard University, where he studied with Dr. Mario Capecchi. He was a Research Assistant Professor at the University of Utah from 1975 to 1976 and was a postdoctoral fellow at Stanford University from 1976 to 1979 in the laboratory of Dr. George Stark. He then joined The Salk Institute as an Assistant Professor in the Molecular Biology and Virology Laboratory. Dr. Wahl received his present appointment as Professor in the Gene Expression Laboratory in 1989. He is also an Adjunct Professor at the University of California, San Diego.

Dr. Wahl's overarching interests concern the mechanisms that initiate tumor formation, and that mediate progression of cells to malignancy. His early research at the Salk Institute involved analyses of the molecular mechanisms of gene amplification, a form of genetic instability that is unique to cancer cells. His laboratory provided the first direct evidence that the process is initiated by DNA breakage that can be stimulated by inappropriate entry of cells into DNA replication. His work then broadened to elucidate the molecular mechanisms that prevent unscheduled cell cycle progression in normal cells as well as to identify and characterize the DNA replication origins at which replication initiates. This work led to the finding that the p53 tumor suppressor plays a key role in linking cell cycle progression to genetic instability. His group showed that p53 is activated under growth challenging conditions to induce either senescence or cell death to prevent variants with genetic instability from arising. These studies led to the concept that p53 is "The Guardian of the Genome". His group also developed molecular genetic strategies to identify, isolate, and characterize mammalian replication origins.

Dr. Wahl has published more than 130 articles, reviews and book chapters related to genetic instability, p53 functions and control, and the control of DNA replication. He has contributed to the development of numerous technologies in wide use in molecular and cellular biology, is the author of a citation classic concerning methods of DNA detection, and is the holder of a number of patents. He serves as a reviewer for major biomedical journals, is on several editorial Boards, has been the co-chair and Program Chair of three Annual meetings of the American Association for Cancer Research (AACR), and was elected as President of AACR for 2006-2007.