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Dannielle Engle

Research

Having lost close family members to pancreatic cancer, Dannielle Engle has a personal connection to the disease. Engle uses her personal and scientific passion as well as her expertise in modeling to facilitate progress in pancreatic cancer research by creating better representations of what actually happens in patients. The identification of biomarkers and therapeutic targets has been hindered by the limited access to pure sample populations and accurate models. When looking at a patient's blood samples, there can be hidden signals from the incipient tumor, but these are masked and diluted by the multitude of other signals from all over the body. In addition, when looking at the pancreatic tumor tissue itself, most of our time is spent looking at signals from non-cancer cell types in the scar-like tissue that takes up the majority of the tumor in human patients. Traditional approaches have used cell lines that do not accurately represent the early stages of pancreatic cancer. Engle tackles these challenges by creating organoid and genetically engineered mouse models to better recapitulate pancreatic disease. Using these systems, the Engle lab identifies new therapeutic targets in organoids and tests their efficacy in autochthonous, immune competent mouse models. In addition, the need for more effective treatment options goes hand-in-hand with the ability to diagnose pancreatic cancer before it spreads. Accordingly, the Engle lab also focuses on the identification of biomarkers that unambiguously differentiate between pancreatic cancer and other inflammatory conditions.

Select Publications

  • Wang, Y. V., Leblanc, M., Fox, N., Mao, J. H., Tinkum, K. L., Krummel, K., . . . Wahl, G. M. (2011). Fine-tuning p53 activity through C-terminal modification significantly contributes to HSC homeostasis and mouse radiosensitivity. Genes & development, 25(13), 1426-1438. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/21724834. doi:10.1101/gad.2024411
  • Spike, B. T., Engle, D. D., Lin, J. C., Cheung, S. K., La, J., & Wahl, G. M. (2012). A mammary stem cell population identified and characterized in late embryogenesis reveals similarities to human breast cancer. Cell stem cell, 10(2), 183-197. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/22305568. doi:10.1016/j.stem.2011.12.018
  • Sherman, M. H., Yu, R. T., Engle, D. D., Ding, N., Atkins, A. R., Tiriac, H., . . . Evans, R. M. (2014). Vitamin D receptor-mediated stromal reprogramming suppresses pancreatitis and enhances pancreatic cancer therapy. Cell, 159(1), 80-93. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/25259922. doi:10.1016/j.cell.2014.08.007
  • Boj, S. F., Hwang, C. I., Baker, L. A., Chio, II, Engle, D. D., Corbo, V., . . . Tuveson, D. A. (2015). Organoid models of human and mouse ductal pancreatic cancer. Cell, 160(1-2), 324-338. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/25557080. doi:10.1016/j.cell.2014.12.021
  • Naguib, A., Bencze, G., Engle, Dannielle D., Chio, Iok I. C., Herzka, T., Watrud, K., . . . Trotman, Lloyd C. (2015). P53 Mutations Change Phosphatidylinositol Acyl Chain Composition. Cell reports, 10(1), 8-19. Retrieved from http://www.sciencedirect.com/science/article/pii/S2211124714010213. doi:http://dx.doi.org/10.1016/j.celrep.2014.12.010
  • Roy, I., McAllister, D. M., Gorse, E., Dixon, K., Piper, C. T., Zimmerman, N. P., . . . Dwinell, M. B. (2015). Pancreatic Cancer Cell Migration and Metastasis Is Regulated by Chemokine-Biased Agonism and Bioenergetic Signaling. Cancer Res, 75(17), 3529-3542. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/26330165. doi:10.1158/0008-5472.CAN-14-2645
  • Zambirinis, C. P., Levie, E., Nguy, S., Avanzi, A., Barilla, R., Xu, Y., . . . Miller, G. (2015). TLR9 ligation in pancreatic stellate cells promotes tumorigenesis. The Journal of experimental medicine, 212(12), 2077-2094. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/26481685. doi:10.1084/jem.20142162
  • Ireland, L., Santos, A., Ahmed, M. S., Rainer, C., Nielsen, S. R., Quaranta, V., . . . Mielgo, A. (2016). Chemoresistance in Pancreatic Cancer Is Driven by Stroma-Derived Insulin-Like Growth Factors. Cancer Res, 76(23), 6851-6863. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/27742686. doi:10.1158/0008-5472.CAN-16-1201
  • Nielsen, S. R., Quaranta, V., Linford, A., Emeagi, P., Rainer, C., Santos, A., . . . Schmid, M. C. (2016). Macrophage-secreted granulin supports pancreatic cancer metastasis by inducing liver fibrosis. Nature cell biology, 18(5), 549-560. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/27088855. doi:10.1038/ncb3340
  • Seifert, L., Werba, G., Tiwari, S., Giao Ly, N. N., Alothman, S., Alqunaibit, D., . . . Miller, G. (2016). The necrosome promotes pancreatic oncogenesis via CXCL1 and Mincle-induced immune suppression. Nature, 532(7598), 245-249. Retrieved from http://dx.doi.org/10.1038/nature17403. doi:10.1038/nature17403
  • Öhlund, D., Handly-Santana, A., Biffi, G., Elyada, E., Almeida, A. S., Ponz-Sarvise, M., . . . Tuveson, D. A. (2017). Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer. The Journal of experimental medicine. Retrieved from http://jem.rupress.org/content/jem/early/2017/02/23/jem.20162024.full.pdf. doi:10.1084/jem.20162024
  • Quaranta, V., Rainer, C., Nielsen, S. R., Raymant, M. L., Ahmed, M. S., Engle, D. D., . . . Schmid, M. C. (2018). Macrophage-Derived Granulin Drives Resistance to Immune Checkpoint Inhibition in Metastatic Pancreatic Cancer. Cancer Res, 78(15), 4253-4269. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/29789416. doi:10.1158/0008-5472.CAN-17-3876
  • Tiriac, H., Belleau, P., Engle, D. D., Plenker, D., Deschênes, A., Somerville, T., . . . Tuveson, D. A. (2018). Organoid profiling identifies common responders to chemotherapy in pancreatic cancer. Cancer discovery. Retrieved from http://cancerdiscovery.aacrjournals.org/content/candisc/early/2018/05/30/2159-8290.CD-18-0349.full.pdf. doi:10.1158/2159-8290.Cd-18-0349
  • Wolff, R. A., Wang-Gillam, A., Alvarez, H., Tiriac, H., Engle, D., Hou, S., . . . Levine, A. J. (2018). Dynamic changes during the treatment of pancreatic cancer. Oncotarget, 9(19), 14764-14790. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/29599906. doi:10.18632/oncotarget.24483
  • Engle, D. D., Tiriac, H., Rivera, K. D., Pommier, A., Whalen, S., Oni, T. E., . . . Tuveson, D. A. (2019). The glycan CA19-9 promotes pancreatitis and pancreatic cancer in mice. Science, 364(6446), 1156-1162. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/31221853. doi:10.1126/science.aaw3145

Biography

Dannielle Engle finished her Ph.D. in the laboratory of Dr. Geoffrey M. Wahl at the Salk Institute for Biological Studies in the Biological Sciences program of the University of California, San Diego. Engle completed her postdoctoral fellowship in the laboratory of Dr. David. A. Tuveson beginning at the Cambridge Research Institute and finishing at Cold Spring Harbor Laboratory as a Senior Fellow. Engle also organized scientific outreach programs as the Lustgarten Foundation Pancreatic Cancer Research Laboratory Ambassador and is a recipient of the Theodore T. Puck and NCI K99/R00 Pathway to Independence Awards. Engle returned to the Salk Institute in 2019 as an Assistant Professor.