Faculty, Graduate Program
All our work is directed at a basic understanding of genetic and epigenetic mechanisms that induce oncogenic transformation of cells. With this information, we conduct screens for small molecules that intervene with the activity of newly identified cancer targets. Our current research focuses on three families of cancer targets: protein and lipid kinases, transcriptional regulators and non-coding, antisense RNA.
Among the kinases, phosphatidylinositol 3-kinase (PI3K) has emerged as an important cancer target, because it is frequently mutated in cancer and because most cancers show increased PI3K activity (1). We have characterized the cancer-specific mutations in PI3K (2-5) and continue to explore basic signaling mechanisms that involve this kinase. We are also engaged in the identification and testing of novel specific inhibitors that interfere with oncogenic PI3K.
In the past, we have conducted extensive studies on the oncogenic activity of transcriptional regulators, including Myc, Jun, β-catenin/LEF, and FKHR. Most of our current activity centers on Myc. We have identified small molecules that interfere with the dimerization of Myc and Max (6-9), and these interfere with Myc-induced oncogenic transformation. We have also successfully restricted Myc activity by stabilizing the Max homodimer, making this essential partner less available for Myc. Work on Myc inhibitors continues in collaboration with industry partners.
Many genes generate long, antisense non-coding transcripts. There is evidence that non-coding RNA is critical in the epigenetic regulation of gene activity (10-12). In collaboration with the lab of Kevin Morris at TSRI, we are studying the role of noncoding RNAs in the activation of oncogenes and the silencing of tumor suppressors (13).
1. Rommel C, et al., editors. Phosphoinositide 3-kinase in Health and Disease. Current Topics in Microbiology and Immunology, Vol.: 346 & 347, 1st ed. Heidelberg: Springer; 2011.
2. Kang S, et al. Cell Cycle 2005; 4: 578-81.
3. Zhao L, et al. Proc Natl Acad Sci U S A 2008; 105: 2652-7.
4. Sun M, et al. Proc Natl Acad Sci U S A 2010; 107: 15547-52.
5. Zhao L, et al. Cell Cycle 2010; 9: 596-600.
6. Berg T, et al. Proc Natl Acad Sci U S A 2002; 99: 3830-5.
7. Xu Y, et al. Bioorg Med Chem 2006; 14: 2660-73.
8. Shi J, et al. Bioorg Med Chem Lett 2009; 19: 6038-41.
9. Prochownik E, et al. Genes & Cancer 2010; 1: 650-9.
10. Morris KV, et al. PLoS Genet 2008; 4: e1000258.
11. Weinberg MS, et al. RNA 2006; 12: 256-62.
12. Morris KV, et al. Science 2004; 305: 1289-92.
13. Morris KV, et al. Cell Cycle 2010; 9: 2542 - 5.
Ph.D., Biology, University of Tübingen, Germany, 1959
B.S., University of Würzburg, Germany, 1955
Ph.D. student, Max Planck Institute, Tübingen, Germany, 1955 - 1959
Ph.D. degree from University of Tübingen, Germany, 1959
Postdoctoral associate, University of California, Berkeley, Virus Laboratory, 1959 – 1962
Assistant and Associate Professor of Pathology, University of Colorado School of Medicine, Denver, 1962 – 1967
Associate Professor and Professor of Microbiology, University of Washington School of Medicine, Seattle, 1967 – 1971
Hastings Distinguished Professor of Microbiology and Chairman, Dept. of Microbiology, USC School of Medicine, Los Angeles, 1971 – 1993
Professor, The Scripps Research Institute, La Jolla, since 1993
Alexander von Humboldt Award, Federal Republic of Germany (1984)
Ernst Jung Prize for Medicine (1985)
Robert J. and Claire Pasarow Award (1987)
Paul-Ehrlich and Ludwig-Darmstaedter Prize (1988)
ICN International Prize in Virology (1989)
Bristol Myers Award (1989)
Charles S. Mott Prize, General Motors Cancer Research Foundation (1991)
Gregor Johann Mendel Medal, National Academy of Sciences of the Czech Republic (2008)
Loeffler-Frosch Medal, German Society of Virology (2010)
Albert Szent-Györgyi Prize for Progress in Cancer Research (2010)
Einstein Professorship, Chinese Academy of Sciences (2013)
Pezcoller Foundation-AACR International Award for Cancer Research (2013)
National Academy of Sciences USA (since 1980)
American Philosophical Society (since 1991)
American Academy of Microbiology (since 1992)
Leopoldina - German National Academy of Sciences (since 1998)
Institute of Medicine (since 2003)American Academy of Arts and Sciences (since 2004)
Current Topics in Microbiology and Immunology (since 1967)
Blood Cells, Molecules & Diseases (since 1995)
Proceedings of the National Academy of Sciences USA (since 2000)
Cell Cycle (since 2005)
Genes and Cancer (since 2009)
OncoTarget (since 2010)
Frontiers in Molecular and Cellular Oncology (since 2010)
Dannemann N, Hart JR, Ueno L, Vogt PK. Phosphatidylinositol 4,5-bisphosphate (PIP(2))-specific AKT1 is oncogenic. Int J Cancer. 2010;127(1):239-44. PMCID: PMC2862841. PMID: 19876913.
Morris KV, Vogt PK. Long antisense non-coding RNAs and their role in transcription and oncogenesis. Cell Cycle. 2010;9(13):2544-2547. PMID: 20581457.
Murphy EA, Shields DJ, Stoletov K, Dneprovskaia E, McElroy M, Greenberg JI, Lindquist J, Acevedo LM, Anand S, Majeti BK, Tsigelny I, Saldanha A, Walsh B, Hoffman RM, Bouvet M, Klemke RL, Vogt PK, Arnold L, Wrasidlo W, Cheresh DA. Disruption of angiogenesis and tumor growth with an orally active drug that stabilizes the inactive state of PDGFRbeta/B-RAF. Proc Natl Acad Sci U S A. 2010;107(9):4299-304. PMCID: 2840076. PMID: 20154271.
Prochownik E, Vogt PK. Therapeutic Targeting of Myc. Genes & Cancer. 2010;1 (6): 650-659. NIHMS: 214858
Shi J, Sun M, Vogt PK. Smooth muscle α-actin is a direct target of PLZF: effects on the cytoskeleton and on susceptibility to oncogenic transformation. OncoTarget. 2010;1(1):9-21. PMCID: 2903758. PMID: 20634973.
Sun M, Hillmann P, Hofmann BT, Hart JR, Vogt PK. Cancer-derived mutations in the regulatory subunit p85a of phosphoinositide 3-kinase function through the catalytic subunit p110a. Proc Natl Acad Sci U S A. 2010;107(35):15547-52. PMCID: 2932613. PMID: 20713702.
Vanhaesebroeck B, Vogt PK, Rommel C. PI3K – From the Bench to the Clinic and Back. Curr Top Microbiol Immunol. 2010 Jun 12. [Epub ahead of print] PMCID: 2954281. PMID: 20549473.
Vogt PK. Oncogenes and the Revolution in Cancer Research - Homage to Hidesaburo Hanafusa (1929 - 2009). Genes & Cancer. 2010;1(1):6-11.
Vogt PK, Hart JR, Gymnopoulos M, Jiang H, Kang S, Bader AG, Zhao L, Denley A. Phosphatidylinositol 3-Kinase: The Oncoprotein. In: Rommel C, Vanhaesebroeck B, Vogt PK, editors. Curr Top Microbiol Immunol. 2010 Jun 26. [Epub ahead of print] PMCID: 2955792. PMID: 20582532.
Zhao L, Vogt PK. Hot-spot mutations in p110alpha of phosphatidylinositol 3-kinase (PI3K): Differential interactions with the regulatory subunit p85 and with RAS. Cell Cycle. 2010;9(3):596-600. PMCID: 2835815. PMID: 20009532.
For a complete list of publications, please visit our laboratory website.