My laboratory is interested in the general problem of identifying small molecules that activate or inhibit specific biological functions and of identifying the molecular targets of such compounds. In particular we are interested in compounds that have more potent activity in cancer cells than normal cells and using them to identify the underlying molecular difference between these cellular states. A focus of the laboratory is to specifically control the membrane traffic pathways that regulate the expression of growth factor receptors on the cell surface, as many cancer cells are particularly dependent upon elevated signaling through these receptors. We employ a number of techniques, including high-throughput screening of chemical compound libraries, to identify compounds of interest, as well as forward and reverse genetic approaches to identify the targets of compounds.
RESEARCH INTERESTS
Intracellular traffic in membrane proteins and lipids.
High-throughput screening of chemical compound libraries.
High-throughput screening of RNAi libraries.
Drug discovery
RECENT PUBLICATIONS
Chen, B., M. Dodge, W. Tang, J. Lu, Z. Ma, C-W. Fan, S. Wei, W. Hao, J. Kilgore, N. Williams, M. G. Roth, J. Amatruda, C. Chen and L. Lum, "Small molecule-mediated disruption of Wnt-dependent signal transduction in tissue regeneration and cancer." Nature Chem. Biol., 5:100-107, 2009
Rasko, D. A. C. G. Moreira, D. Li, J. M. Ritchie, M. K. Waldor, N. Williams, R. Taussig, C. Mischnoff2, S. Wei, M. G. Roth, D. T. Hughes, J. Huntley, J. R. Falck, and V. Sperandio, "Targetting QseC Signaling and Virulence for Antibiotic Development" Science, 321:1078-1080, 2008
Tang, W., M. Dodge, D. Gundapaneni, C. Michnoff, M. G. Roth and L. Lum., "A genome-wide RNAi screen for mammalian Wnt/beta-catenin pathway components identifies novel roles for TCF transcription factors in tumorigenesis." Proc. Natl. Acad. Sci. USA., 105:9709-9714, 2008
Padron, D., M. Sato, J. W. Shay, A. F. Gazdar, J. D. Minna, and M. G. Roth., "Mutations in Lung Cancer Inhibit Receptor Downregulation by Disruption of Cbl-mediated Ubiquitylation." Can. Res., 16:7695-7702., 2007
Whitehurst, A. W., B. O. Bodemann, J. Cardenas, D. Ferguson, L. Girard, M. Payton, J. D. Minna, C. Michnoff, W. Hao, M. G. Roth, X.-J. Xie, and M. A. White., "Synthetic Lethal Screen Identification of Chemosensitizer Loci in Cancer Cells." Nature, 446:815-819, 2007
SIGNIFICANT PUBLICATIONS
Chen, B., M. Dodge, W. Tang, J. Lu, Z. Ma, C-W. Fan, S. Wei, W. Hao, J. Kilgore, N. Williams, M. G. Roth, J. Amatruda, C. Chen and L. Lum, "Small molecule-mediated disruption of Wnt-dependent signal transduction in tissue regeneration and cancer." Nature Chem. Biol., 5:100-107, 2009
Whitehurst, A. W., B. O. Bodemann, J. Cardenas, D. Ferguson, L. Girard, M. Payton, J. D. Minna, C. Michnoff, W. Hao, M. G. Roth, X.-J. Xie, and M. A. White, "Synthetic Lethal Screen Identification of Chemosensitizer Loci in Cancer Cells." Nature, 446:815-819, 2007
Melkonian, K. A., A. G. Ostermeyer, J. Z. Chen, M. G. Roth, D. A. Brown., "Role of lipid modifications in targeting proteins to detergent-resistant membrane domains: acylation can target proteins to the membranes, while prenylated proteins are excluded." J. Biol. Chem., 274:3910-3917, 1999
Brewer, C. B. and M. G. Roth, "A single amino acid change in the cytoplasmic domain alters the polarized delivery of the influenza virus hemagglutinin." J. Cell Biol., 114:413-421, 1991
Lazarovits, J., and M. G. Roth, "A single amino acid change in the cytoplasmic domain allows the influenza virus hemagglutinin to be endocytosed through coated pits." Cell., 53:743-752, 1988
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