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.
RECENT PUBLICATIONS
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
Zubovych, I., T. Doundoulakis, P. G. Harran and M. G. Roth, "A missense mutation in Caenorhabditis elegans prohibitin 2 confers an atypical multidrug resistance" Proc. Natl. Acad. Sci. USA, 103:15523-15528, 2006
Padron, D., R. Tall, M. G. Roth, "Phospholipase D2 is required for efficient endocytic recycling of transferrin receptors" Mol. Biol. Cell, 17:598-606, 2006
Baldwin, J., C. H. Michnoff, N. A. Malmquist, J. White, M. G. Roth, P. K. Rathod and M. A. Phillips, "High-throughput screening for potent and selective inhibitors of Plasmodiumn falciparum dihydroorotate dehydrogenase" J. Biol. Chem., 280:21847-21853, 2005
SIGNIFICANT PUBLICATIONS
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
Ktistakis, N. T., H.A. Brown, M. G. Waters, P. A. Sternweis and M. G. Roth, "Evidence that phospholipase D mediates ARF-dependent formation of Golgi coated vesicles." J. Cell Biol., 134:295-305, 1996
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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