- Lauren E. Ball, Ph.D.
- Joe B. Blumer, Ph.D.
- Warren Davis Jr., Ph.D.
- Scott Eblen, Ph.D.
- Perry V. Halushka, M.D., Ph.D.
- John D. Hildebrandt, Ph.D.
- Jennifer S. Isaacs, Ph.D.
- Daniel R. Knapp, Ph.D.
- David T. Kurtz, Ph.D.
- Stephen M. Lanier, Ph.D.
- Carola A. Neumann, M.D.
- John E. Oatis, Ph.D.
- Steven A. Rosenzweig, Ph.D.
- Kevin L. Schey, Ph.D.
- Kenneth D. Tew, Ph.D., D.Sc.
- Thomas Walle, Ph.D.
- Michael J. Wargovich, Ph.D.
- Jerry G. Webb, Ph.D.
Thomas Walle, Ph.D.
Professor
Cell and Molecular PharmacologyPh.D.(Farmacie Licentiat), Royal Institute of Pharmacy, Sweden, 1968
wallet@musc.edu
Tel: 843-792-2507
Fax: 843-792-2475
Walle Lab
Cancer Prevention
The research in this laboratory is focused on understanding the initiation as well as promotion stages of chemically-induced carcinogenesis in epithelial cells, e.g. oral, esophageal and lung, and the development of strategies for prevention of these cancers by dietary flavonoids. One area of interest is the extent and mode of binding of major carcinogens, such as the polyaromatic hydrocarbons to cellular DNA. This is determined by the balance between bioactivating enzymes, e.g. cytochrome P4501B1 and 1A1, and bioinactivating enzymes, e.g. UDP-glucuronosyltransferases. We have found that flavonoids inhibit and/or induce these enzymes by varying mechanisms, including the aryl hydrocarbon receptor (AhR).
Another area of interest is the uncontrolled growth of the preneoplastic cells following carcinogen initiation. We are determining the ability of flavonoids to inhibit the preneoplastic cell proliferation as well as to induce cell cycle changes and apoptosis. This appears to happen through interaction with a variety of signal transduction pathways, such as amphiregulin, EGFR and various kinases. Limited bioavailability of the flavonoids is of great concern when extending this research to animal models as well as to humans. Studies of cell membrane transport and cellular metabolism of the flavonoids together with microscopic techniques, using well-established cell culture models are therefore of key importance. Several novel compounds, in particular methylated flavones, which are resistant to metabolism, are pursued as potential new drugs.
Selected Publications | Additional Publications
Wen X. and T. Walle: Methylation protects dietary flavonoids from rapid hepatic metabolism. Xenobiotica 36:387-397, 2006.
Walle T., U. K. Walle, D. Sedmera and M. Klausner: Benzo[α]pyrene-induced oral carcinogenesis and chemoprevention - studies in bioengineered human tissue. Drug Metab. Dispos. 34:346-350, 2006.
Haghiac M. and T. Walle: Quercetin induces necrosis and apoptosis in SCC-9 oral cancer cells. Nutr. Cancer 53:220-231, 2005.
Wen X. and T. Walle: Preferential induction of CYP1B1 by benzo[α]pyrene in human oral epithelial cells: Impact on DNA adduct formation and prevention by polyphenols. Carcinogenesis 26:1774-1781, 2005.
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