Stem cells in normal and cancerous growth; gene control pathways relevant to normal development and cancer; development of new cancer therapies
Dr. Wahl obtained a B.A. in Bacteriology from the University of California, Los Angeles, his PhD in Biological Chemistry from Harvard University, and was a a postdoctoral fellow at Stanford University. He joined The Salk Institute and became Professor in the Gene Expression Laboratory in 1989.
His research focuses on two important problems related to cancer biology. The first concerns the p53 signal transduction pathway that ensures the control of genetic stability in normal cells and is invariably disrupted during cancer progression. An important objective of this work involves development of therapeutic strategies based on selective killing of cancers encoding wild type p53. A second project involves determining relationships between the “state of stemness” and cancer. This project has identified, isolated, and characterized the stem cells generated in the embryonic mammary rudiment to determine whether such cells share properties with stem-like cells in breast cancer. This type of approach also has significant therapeutic potential. Dr. Wahl has published more than 150 articles and reviews related to genetic instability, p53 functions, the control of DNA replication, and the stem cell state and cancer. His lab has developed many technologies in wide use in molecular and cellular biology. He is a Fellow of the AAAS, was appointed as a Susan G. Komen Scholar, and served as President of the American Association for Cancer Research.
Toledo, F., Krummel, K.A., Lee, C.J., Liu, C.W., Rodewald, L.W., Tang, M. and Wahl, G.M. (2006) A Mouse p53 Mutant Lacking The Proline-Rich Domain Rescues Mdm4 Deficiency and Provides Insight Into The Mdm2-Mdm4-P53 Regulatory Network. Cancer Cell 9:273-285.
Toledo, F. and Wahl, G.M. (2006) Regulating The p53 Pathway: in vitro Hypotheses, in vivo Veritas. Nat. Rev. Canc. 6:909-923.
Wang, Y.V., Wade, M., Wong, E.T., Li, Y-C., Rodewald, L.W., and Wahl, G.M. (2007) Quantitative Analyses Reveal the Importance Of Regulated Hdmx Degradation for p53 Activation. Proc. Natl. Acad. Sci. Published Online Before Print July 17, 2007. 104(30):12365-12370.
Wang, Y.V., Leblanc, M., Wade, M., Jochemsen, A.G., and Wahl, G.M. (2009) Increased radio-resistance and accelerated B-cell lymphomas in mice with Mdmx mutations that prevent modifications by DNA damage-activated kinases. Cancer Cell 16:33-43.
Kawamura, T., Suzuki, J., Wang, Y.V., Menendez, S., Morera, L.B., Wahl, G.M, and Belmonte, J.C. (2009) Linking the p53 pathway to somatic cell reprogramming. Nature 460:1140-1144.
Mizuno, M., Benjamin T. Spike, Wahl, G.M., and Levine, A.J. (2010) p53 Inactivation in Breast Cancers Correlates with Stem Cell Transcriptional Signatures. PNAS: 107(52):22745–22750.
Bernal F, Wade M, Godes M, Davis TN, Whitehead DG, Kung AL, Wahl GM, Walensky LD. A Stapled p53 Helix Overcomes HDMX-Mediated Suppression of p53. Cancer Cell. 2010 18:411-422.
Wang, Y.V., Fox, N., Leblanc, M., Mao, J., Balmain, A., Kaushansky, K., and Wahl, G.M. (2011) Fine tuning p53 activity is a critical determinant of stem cell homeostasis and radiosensitivity in the hematopoietic system. Genes Dev Jul 1;25(13):1426-1438.
Benjamin T. Spike and Wahl, G.M. (2011) p53, Stem Cells, and Reprogramming: Tumor Suppression beyond Guarding the Genome. Genes Cancer. 2011 April; 2(4): 404–419.
Lin, J., Engle, D.*, Spike, B.T.*, La, J., Cheung, S., and Wahl, G.M. (2011) Identification, isolation, and characterization of fetal mammary stem cells: late emergence in embryogenesis and relationship to human breast cancer *equal contribution (in revision).