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Cancer Therapeutics Branch
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Phillip A. Dennis, M.D., Ph.D.
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| Principal Investigator |
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Building 8, Room 5101
National Naval Medical Center
8901 Wisconsin Ave.
Bethesda, AL 20889 |
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Phone:
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301-496-0929 |
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Fax:
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301-496-0047 |
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E-Mail:
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pdennis@nih.gov |
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| Dr. Dennis received his B.A. in 1984 from the University of Virginia and his Ph.D. and M.D. degrees in 1991 and 1992, respectively, from the New York University School of Medicine as part of the Medical Scientist Training Program. He completed his internal medicine training on the Osler Medical Service at Johns Hopkins Hospital. Following his residency, he completed a fellowship in medical oncology at the Johns Hopkins Oncology Center and then joined the laboratory of Michael Kastan where he developed an interest in molecular control of apoptosis. Dr. Dennis joined the NCI in October 1998. |
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Research
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Activation of the PI3K/Akt pathway and the biology of lung cancer
The objective of our laboratory is to understand the molecular determinants of cellular survival that allow normal lung epithelial cells to escape programmed cell death (apoptosis) during tobacco-induced carcinogenesis and allow lung cancer cells to evade apoptosis when they are exposed to chemotherapy or irradiation. Identifying specific molecules that promote survival will provide new, attractive targets for the development of compounds that abrogate survival signals, halt tumorigenesis, and enhance therapeutic effectiveness.
Our laboratory has completed a systematic analysis of lung cancer cells that identified signaling pathways that are utilized by these cells to promote cellular survival and resistance to chemotherapy and radiation. We used pharmacologic and genetic approaches to identify three signaling cascades- the PI3K/Akt pathway, the MEK/ERK pathway, and the PKC pathway- that contribute to lung cancer cell survival and therapeutic resistance. More recently, we have shown that tobacco components activate the PI3K/Akt pathway, increase cell survival, and partially induce a transformed phenotype in primary human lung epithelial cells. Activation of Akt and downstream components increases with the phenotype progression of human and murine lung lesions induced by a tobacco carcinogen. Together, these studies are consistent with hypothesis that Akt serves as a biochemical gatekeeper for lung carcinogenesis.
Current studies in the laboratory are focused on: (1) mechanism of activation of the PI3K/Akt pathway by tobacco components; (2) the development of relevant murine model systems; (3) the assessment of active components in the PI3K/Akt pathway in human and animal tissues; and (4) the development of novel therapeutic approaches to inhibit Akt.
Our collaborators in this work are Stephen Hewitt, Curtis C. Harris, NCI; Abdel Elkahloun, NHGRI; and Alan Kozikowski, University of Illinois at Chicago. |
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| This page was last updated on 5/20/2004. |
