The broad goal of our research is to contribute to uncovering the molecular nature of cell autonomous regulatory mechanisms permitting appropriate responses of human cells to their environment. These mechanisms are ultimately responsible for initiating correct developmental and adaptive changes in cell behavior. Aberrant regulation of these mechanisms results in pathological changes that are responsible for initiating a wide variety of human diseases including cancer. Our focus has been on the contribution of Ras-family small GTPases to the regulation of proliferation, differentiation, and oncogenic transformation. Our work has shown that these proteins act as key nodes in signal transduction networks, integrating extracellular and intracellular cues to the activation of appropriate machinery driving the response of cells to those cues. We are defining the composition, organization, and regulation of the Ras GTPase signaling network. We are using this information to establish paradigms describing the nature of signal-mediated information flow and connectivity to cell biological responses. With respect to human disease, we are translating our observations into a molecular understanding of the establishment of a minimal tumorigenic platform in general, and into defining the critical contribution of Ras oncogenes to initiation and maintenance of human cancer in particular.
RESEARCH INTERESTS
Molecular architecture of growth regulatory signal transduction cascades
Cancer
Signal transduction
Oncogenes
Tumor Suppressors
RECENT PUBLICATIONS
Bumeister, R., Rosse, C., Anselmo, A., Camonis, C., and White, M. A., "CNK2 Couples NGF Signal Propagation to Multiple Regulatory Cascades Driving Cell Differentiation" Current Biology, 14:439-445, 2004
Matheny, S., Chen, C., Kortum, R., Razidlo, G., Lewis, R., and White, M. A., "Ras regulates assembly of mitogenic signaling complexes through the novel effector protein IMP." Nature, 427:256-260, 2004
Whitehurst, A., Cobb, M., and White, M. A., "Stimulus-coupled spatial restriction of ERK1/2 activity contributes to the specificity of signal/response pathways." Mol. Cell. Biol., 24:10145-10150, 2004
Chien Y, Kim S, Bumeister R, Loo YM, Kwon SW, Johnson CL, Balakireva MG, Romeo Y, Kopelovich L, Gale M Jr, Yeaman C, Camonis JH, Zhao Y, White MA, "RalB GTPase-mediated activation of the IkappaB family kinase TBK1 couples innate immune signaling to tumor cell survival" Cell, 6:157-170, October 2006
Whitehurst, A. W., Bodemann, B. O., Cardenas, J., Ferguson, D., Girard, L., Payton, M., Minna, J. D., Michnoff, C., Hao, W., Roth, M. G., Xie X.-J., and White, M. A., "Functional genomics of chemosensitivity exposes deviant cancer cell regulatory systems." Nature, 446:815-820, 2007
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