David A. Foster

Professor of Biology and Biochemistry

E-mail - Foster@genectr.hunter.cuny.edu
Office - Room 906a,   (212) 772-4075
Lab - Rooms 905/906/908/910,   (212) 772-5226/4594

Education:

A.B.                 1976                            University of California, Berkeley
Ph.D.               1982                              Columbia University
Postdoc           1982-86                          The Rockefeller University

Research Interests:

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.

The lab is also investigating the role of another enzyme – protein kinase Cd (PKCd), which suppresses survival signaling and has been proposed to be a tumor suppressor gene. PKCd is also activated in response to apoptotic signals. Interestingly, the PKCd gene is localized to a region of chromosome 3p that is frequently deleted in a variety of human cancers.   Strategies for activating PKCd to induce apoptosis and suppress tumor growth are being investigated.

Selected Publications :

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

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.

Joseph, T., Bryant, A., Wooden, R., Kerkhoff, E., Rapp, U.R. and Foster, D.A. (2002). Phospholipase D overcomes cell cycle arrest induced by high-intensity Raf signaling. Oncogene 21, 3651-3658.

Xu, L., Frankel, P., Jackson, D., Rotunda, T., DSouza-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.  

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.

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.

Abbas, T., White, D., Hui, L., Foster, D.A. and Jill Bargonetti, J. (2004). Inhibition of p53 transcription by down-regulation of protein kinase C d. J. Biol. Chem. 279, 9970-9977.

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.

Foster, D.A. (2004). Targeting mTOR-mediated survival signals in anticancer therapeutic strategies.  Exp. Rev. Anticancer Ther. 4, 691-701.

Chen, Y., Rodrik, V. and Foster, D.A. (2005). Alternative phospholipase D / mTOR survival signal in human breast cancer cells. Oncogene 24, 672-679.

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.

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.

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.

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.

Foster, D.A. (2006). Phospholipase D survival signals as a therapeutic target in cancer. Current Signal Transduction Ther. 1, 295-303.

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. (2007). Regulation of mTOR by phosphatidic acid? Cancer Res. 67, 1-4.