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.
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.
Spike, B.T., Engle, D., Lin, J., Cheung, S., and Wahl, G.M. (2012) A mammary stem cell population identified and characterized in late embryogenesis reveals similarities to human breast cancer. Cell-Stem-Cell. Volume 10, Issue 2, 183-197. PMCID: PMC3277444
Green, J.L., Bauer, M. Yum, K.W., Li, Y-C., Cox, M.L., Willert, K., and Wahl, G.M. (2013) Use of a Molecular Genetic Platform Technology to Produce Human Wnt Proteins Reveals Distinct Local and Distal Signaling Abilities. PLoS One, 8(3):e58395. PMCID: PMC3596392
Green, J.L., La, J., Yum, K.W., Desai, P., Rodewald, L.W., Zhang, X., Leblanc, M., Nusse, R., Lewis, M.T., and Wahl, G.m. (2013). Paracrine Wnt signaling both promotes and inhibits human breast tumor growth. Proc. Natl. Acad. Sci. U.S.A. 110(17):6991-6 (PMCID: In Process)
Makarem, M., Spike, B.T., Dravis, C., Kannan, N., Wahl, G.M., and Eaves, C.J. (2013) Stem cells and the developing mammary gland. J Mammary Gland Biol Neoplasia, 18(2):209-19. doi: 10.1007/s10911-013-9284-6. Epub 2013 Apr 27. (PMCID in process)