Geoffrey M. Wahl, PhD
2012-2013 BCRF Project:
(made possible by generous support from Michael Reese Enterprises)
Professor, Gene Expression Laboratory
The Salk Institute
La Jolla, CA
Read more about Dr. Wahl's work in Science Daily
Dr. Wahl's team recently obtained and characterized, for the first time, a population of cells highly enriched for the breast tissue stem cells that form during development. These cells are the antecedents of all the adult breast tissue in the organism. Dr. Wahl's team found that the growth regulatory networks in laboratory models are also present in some of the most lethal forms of human breast cancer, including those designated "triple negative." They used sophisticated, novel, and state-of-the-art techniques to decipher these gene regulatory networks and are now refining their computational analyses and their cellular, molecular and genetic strategies to pinpoint the pathways upon which normal breast stem cells rely for their growth and survival. Dr. Wahl expects that elucidating the growth and survival pathways that govern normal breast stem cell function will lead to new therapeutic targets for their mutant counterparts in lethal breast cancers that currently lack effective treatment strategies.
Mid-year Progress: In their recent published work, Dr. Wahl's laboratory reported the interesting finding that the genetic pathways regulating many aspects of the growth, survival, and ability of breast cancer stem cells to communicate to other cells and to their surrounding environment are present in diverse human breast cancers, including those designated "triple negative." Triple negative breast cancer is so named because it lacks estrogen and progesterone receptors and does not have HER2 overexpression, which are molecular features used to define the other classifications of breast cancer. As triple negative breast cancers lack molecularly targeted therapeutics, and often develop resistance to standard chemotherapy, one of Dr. Wahl's goals is to learn which growth and death pathways are most critical to the developing mammary stem cells. Dr. Wahl's team will then exploit these pathways to develop new molecularly targeted therapies to use on these cancers.
Dr. Wahl's team has proposed two specific aims to achieve this important goal. First, they proposed to improve the isolation and growth conditions for developing mammary stem cells to provide the researchers with enough cells of sufficient purity to enable detailed molecular and physiological studies. Second, they wanted to develop methods enabling them to determine every gene these stem cells express, and to use this knowledge to identify markers enabling them to purify and localize these stem cells during normal and tumor growth, and to deduce critical growth and survival pathways amenable to therapeutic intervention. Dr. Wahlâ€™s team has made significant progress in both aims over the past six months. They also developed new approaches to both accelerate attainment of their objectives and to open up new research directions.
Dr. Wahl is a Professor in the Gene Expression Laboratory at the Salk Institute. His research concerns the cellular and genetic basis 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.