Geoffrey Wahl

Research

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 postdoctoral fellow at Stanford University. He joined The Salk Institute and became Professor in the Gene Expression Laboratory in 1989.

His research focuses on three important problems related to cancer biology. The first project involves determining relationships between the “state of stemness” and cancer. This project identified, isolated, and characterized the stem cells generated in the embryonic mammary rudiment and showed that the transcriptomes of these cells share properties with stem-like cells in breast cancer. Recent work has deciphered the epigenomes of normal and cancerous breast cells, showed how they are related, and demonstrated a new mechanism of metastasis involving cell state reprogramming. The second project involves studying protein-protein interactions and their impact on signal transduction. These studies have used a powerful platform for identifying protein interactions in living cells in real time, and have impacted our understanding of the p53, Myc, and Ras pathways. The third project deals with pancreatic cancer. Here, we are studying how changes in the cancerous epithelium affect the non-cancerous cells in the stroma to affect growth of the pancreatic cancer as an aberrant organ. These studies are revealing previously unexpected patterns of cell state reprogramming, and the impact of tuft cells on the immune microenvironment and cancer progression. All of this research 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.

Publications

  • Saison-Ridinger, M., DelGiorno, K.E., Zhang, T., Kraus, A., French, R., Jaquish, D., Tsui, C., Erikson, G., Spike, B.T., Shokhirev, M.N., Liddle, C., Yu, R.T., Downes, M., Evans, R.M., Saghatelian, A., Lowy, A.M., Wahl, G.M. Reprogramming pancreatic stellate cells via p53 activation: A putative target for pancreatic cancer therapy. PLos One 12(12):e0189051. doi: 10.1371/journal.pone.0189051. PMCID:PMC5718507
  • Wahl, G.M. and Spike, B.T. (2017) Cell state plasticity, stem cells, EMT, and the generation of intra-tumoral heterogeneity. NPJ Breast Cancer, 3:14. PMCID: PMC5460241. doi:10.1038/s41523-017-0012-z
  • Turner, K.M., Deshpande, V., Beyter, D., Koga, T., Rusert, J., Lee, C., Li, B., Arden, K., Ren, B., Nathanson. D.A., Kornblum, H.I., Taylor, M.D., Kaushal, S., Cavenee. W.K., Wechsler-Reya, R., Furnari, F.B., Vandenberg, S.R., Rao, P.N., Wahl, G.M., Bafna, V., Mischel, P.S. (2017) Extrachromosomal oncogene amplification drives tumour evolution and genetic heterogeneity. Nature. 543(7643):122-125. PMCID: PMC5334176
  • Sancho-Martinez, I., Nivet, E., Xia, Y., Hishida, T., Aguirre, A., Ocampo, A., Ma, L., Morey, R., Krause, M.N., Zembrzycki, A., Ansorge, O., Vazquez-Ferrer, E., Dubova, I., Reddy, P., Lam, D., Hishida, Y., Wu, M.-Z., Rodriguez Esteban, C., O’Leary, D., Wahl, G.M., Verma, I. M., Laurent, L. C. and Izpisua Belmonte, J.C. (2016) Establishment of human iPSC-based models for the study and targeting of glioma initiating cells. Nature Communications. 7:10743. PMCID: PMC4764898
  • Dravis, C., Spike, B.T., Harrell, C.J., Johns, C., Trejo, C., Southard-Smith, M.E., Perou, C.M. and Wahl, G.M. (2015) Sox10 regulates stem cell and mesenchymal states in mammary epithelial cells. Cell reports, pii: S2211-1247(15)00925-0. PMCID: PMC4591253
  • Pfefferle, A.D., Spike, B.T., Wahl, G.M. and Perou, C.M. (2015) Luminal progenitor and fetal mammary stem cell expression features predict breast tumor response to neoadjuvant chemotherapy. Breast Cancer Res Treat., 149: 425–437. PMCID: PMC4308649
  • Li, Y-C., Rodewald, L.W., Hoppmann, C., Wong, E.T., Lebreton, S., Safar, P., Patek, M., Wang, L., Wertman, K.F., and Wahl, G.M. (2014) A versatile platform to analyze low-affinity and transient protein-protein interactions in living cells in real time. Cell Reports, 9(5):1946-58. doi: 10.1016/j.celrep.2014.10.058. Epub 2014 Nov 20. PMCID: PMC4269221
  • 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:PMC4161372
  • 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:PMC3637696
  • 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