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David A. Foster

Rosalyn Yallow Professor
Department :
Membership :
Full Member
Core Research :
Office :
Belfer BB-432
Email :
Office Phone :
Lab Web Site :
Education :
  • A.B., University of California, Berkeley, 1976
  • M.A., Columbia University, 1978
  • Ph.D., Columbia University, 1982
  • Postdoc, The Rockefeller University, 1982-1986
Research Interest :

Cancer Biology
The goal of our research effort is to understand the biology of cancer cells. From an understanding of the defects in a cancer cell, rational strategies for treatment can be developed. The progression from a normal cell that is responsive to its environment, to a tumor cell that proliferates uncontrollably, requires several genetic alterations to overcome built in protections against unwanted cell proliferation and cancer. Perhaps the most important protection against cancer is a program for cell suicide called apoptosis. Apoptosis is a default response to excess DNA damage or inappropriate cell division signals. To overcome the cells ability to commit suicide, cancer cells must acquire mutations that result in the activation of what are known as “survival signals” that suppress default apoptotic programs. Survival signals in cancer cells are ideal targets for therapeutic intervention because – in principle – suppression of survival results in apoptosis. Our lab has been working on survival signals generated by phospholipase D (PLD), an enzyme whose metabolic product phosphatidic acid suppresses apoptosis induced by both DNA damage and partial cell division signals. Importantly, elevated PLD has been observed in several human cancers including breast, gastric, colon, lung, pancreatic and renal cancer. Our recent work has indicated that inhibiting the signals generated by PLD in breast cancer cells leads to apoptosis, suggesting that PLD could be a good therapeutic target in cancers where PLD signals are keeping the cancer cells alive. PLD and phosphatidic acid contribute to the activation of an enzyme known as mTOR (the mammalian target of rapamycin), which has also been implicated in cancer cell survival signaling. Importantly, mTOR can be targeted with rapamycin and rapamycin induces apoptosis in human cancer cells that are surviving because of their PLD activity. The lab is currently trying to evaluate the potential for targeting PLD and mTOR in cancer cells with elevated PLD activity.

Selected Publications :
  • Lyo, D., Xu, L., and Foster, D.A. (2010). Phospholipase D stabilizes HDM2 through an mTORC2/SGK1 pathway. Biochem. Biophys. Res. Comm. 396, 562-565.
  • Foster, D.A. (2010). Reduced mortality and moderate alcohol consumption: The phospholipase D-mTOR connection. Cell Cycle, 9,1291-4
  • Roberts, A.M., Watson, I.R., Evans, A.G., Foster, D.A., Irwin, M.S., and Ohh, M. (2009). Suppression of HIF2a Restores p53 activity via HDM2 and reverses chemoresistance of renal carcinoma cells. Cancer Res. 69, 9056-9064.
  • Foster, D.A., and Darnell, J.E. Jr. Obituary: Hidesaburo Hanafusa (1929-2009) (2009). Nature. 458, 718.
  • Foster, D.A. (2009). Phosphatidic acid signaling to mTOR: Signals for the survival of human cancer cells. Biochem. Biophys. Acta. 1791, 949-955.
  • Foster, D.A. and Toschi, A. (2009). Targeting mTOR with Rapamycin: One Dose does not Fit All. Cell Cycle. 8, 1026-1029.
  • Toschi, A., Lee, E., Xu, L., Garcia, A., Gadir, N., and Foster, D.A. (2009). Regulation of mTORC1 and mTORC2 complex assembly by phosphatidic acid – a competition with rapamycin. Mol. Cell. Biol. 29, 1411-1420.
  • Toschi, A., Lee, E., Gadir, N., Ohh, M., and Foster, D.A. (2008). Differential dependence of HIF1a and HIF2a on mTORC1 and mTORC2. J. Biol. Chem. 283, 34495 - 34499.
  • Gadir, N., Jackson, D., Lee, E., and Foster, D.A. (2008). Defective TGF-? signaling sensitizes human cancer cells to rapamycin. Oncogene 27, 1055-1062.
  • Toschi, A., Edelstein, J., Rockwell, P., Ohh, M., and Foster, D.A. (2008). HIF? expression in VHL deficient renal cell carcinoma cells is dependent on phospholipase D. Oncogene, 27, 2746-2753.
  • Garcia, A., Zheng, Y., Zhao, C., Toschi, A., Fan, J., Schreibman, N., Brown, H.A., Bar-Sagi, D., Foster, D.A., and Arbiser, J. (2008). Honokiol suppresses survival signals mediated by Ras-dependent phospholipase D activity in human cancer cells. Clinical
  • Foster, D.A., and Gadir, N. (2008). Can defective TGF-? signaling be an Achilles heel in cancer? Chinese Journal of Cancer. 27, 882-884.
  • Mor, A., Campi, G., Du, G., Zheng, Y., Foster, D.A., Dustin, M.L., and Philips, M., (2007). The lymphocyte function associated-1 receptor co-stimulates plasma membrane Ras via phospholipase D2. Nature Cell Biol. 9, 713-719.
  • Shi, M., Zheng, Y., Garcia, A., and Foster, D.A. (2007). Phospholipase D provides a survival signal in human cancer cells with activated H-Ras or K-Ras. Cancer Lett, in press.
  • Gadir, N., Lee, E., Garcia, A., Toschi, A., and Foster, D.A. (2007). Suppression of TGF-? Signaling by phospholipase D. Cell Cycle 6, 2840-2845.
  • Foster, D.A. (2007). Regulation of mTOR by phosphatidic acid? Cancer Res. 67, 1-4.
  • Rodrik, V., Gomes, E., Hui, L., Rockwell, P., and Foster, D.A. (2006). Myc stabilization in response to estrogen and phospholipase D in MCF-7 breast cancer cells. FEBS Lett. 580, 5647-5652.
  • Hui, L., Zheng, Y., Yan, Y., Bargonetti, J., and Foster, D.A. (2006). Mutant p53 in MDA-MB-231 breast cancer cells is stabilized by elevated phospholipase D activity and contributes to survival signals generated by phospholipase D. Oncogene 25, 7305-7310.
  • Foster, D.A. (2006). Phospholipase D survival signals as a therapeutic target in cancer. Current Signal Transduction Ther. 1, 295-303.
  • Zheng, Y., Rodrik, V., Toschi, A., Shi, M., Hui. L., Shen, Y., and Foster, D.A. (2006). Phospholipase D couples survival and migration signals in response to stress in human breast cancer cells. J. Biol. Chem. 281, 15862-15868.
  • Hui, L., Rodrik, V., Pielak, R.M., Zheng, Y., and Foster, D.A. (2005). mTOR-dependent suppression of protein phosphatase 2A is critical for phospholipase D survival signals in human breast cancer cells. J. Biol. Chem. 280, 35829-35835.
  • Rodrik, V., Zheng, Y., Harrow, F., Chen, Y., and Foster, D.A. (2005). Survival signals generated by estrogen and phospholipase D in MCF-7 breast cancer cells are dependent on Myc. Mol. Cell. Biol. 25, 7917-7925.
  • Jackson, D., Zheng, Y., Lyo, D., Shen, Y., Nakayama, K., Nakayama, K.I., Humphries, M., Reyland, M.E., and Foster, D.A. (2005). Suppression of cell migration by protein kinase Cd. Oncogene. 24, 3067-3072.
  • Chen, Y., Rodrik, V. and Foster, D.A. (2005). Alternative phospholipase D / mTOR survival signal in human breast cancer cells. Oncogene 24, 672-679.
  • Foster, D.A. (2004). Targeting mTOR-mediated survival signals in anticancer therapeutic strategies. Exp. Rev. Anticancer Ther. 4, 691-701.
  • Hui, L. Abbas, T., Pielak, R., Bargonetti, J. and Foster, D.A. (2004). Phospholipase D elevates the level of MDM2 and suppresses DNA damage-induced increases in p53. Mol. Cell. Biol. 24, 5677-5686.
  • Jackson, D., and Foster, D.A. (2004). The enigmatic protein kinase C d: Complex roles in cell proliferation and survival. FASEB J. 18, 627-636.
  • Xu, L., Frankel, P., Jackson, D., Rotunda, T., D'Souza-Schorey, C., and Foster, D.A. (2003). Elevated phospholipase D activity in H-Ras-, but not K-Ras-transformed cells by the synergistic action of RalA and Arf6. Mol. Cell. Biol. 23, 645-654.
  • Zhong, M., Shen, Y., Zheng, Y., Joseph, T., Jackson, D., Beychenok, S., and Foster, D.A. (2003) Phospholipase D prevents apoptosis in v-Src-transformed rat fibroblasts and MDA-MB-231 breast cancer cells. Biochem. Biophys. Res. Comm. 302, 615-619.
  • Chen, Y., Zheng, Y., and Foster, D.A. (2003) Phospholipase D confers rapamycin resistance in human breast cancer cells. Oncogene. 22, 3937-3942.
  • Foster, D.A. and Xu, L. (2003). Phospholipase D in cell proliferation and cancer. Mol. Cancer Res. 1, 789-800.
  • Shen, Y., Xu, L., and Foster, D.A. (2001). Role for phospholipase D in receptor-mediated endocytosis. Mol. Cell. Biol. 21, 595-602.
  • Zhong, M., Lu, Z., and Foster, D.A. (2002). Downregulating PKC d provides a PI3K/Akt-independent survival signal that overcomes apoptotic signals generated by c-Src overexpression. Oncogene 21, 1071-1078.
  • Lu, Z., Hornia, A.,Joseph, T., Sukezane, T., Frankel, P., Zhong, M., Bychenok, S., Xu, L. Feig, L.A., and Foster, D.A. (2000). Phospholipase D and RalA Cooperate with the EGF Receptor to Transform 3Y1 Rat Fibroblasts. Mol. Cell. Biol. 20, 462-467.
  • Xu, L., Shen, Y., Joseph, T., Luo, J.-Q., Frankel, P., Rotunda, T., and Foster, D.A. (2000). Elevated phospholipase D activity in transformed cells is restricted to caveolin-enriched membrane microdomains: Biochem. Biophys. Res. Comm. 273, 77-83.