Professor
Ph.D., Catholic University of Leuven, 1991

Signal transduction; Ras and Rho proteins; tumorigenesis; neuronal development and disorders

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My research is focused on signal transduction pathways involving members of the Ras and Rho GTPases and the physiological processes they regulate. These proteins play key roles in cellular activities controlling cellgrowth control, differentiation and morphogenesis. Alterations that affect normal Ras and Rho function result inthe development of several diseases including cancer and neuropathologies. Our efforts are centered on defining therole and mechanisms by which Ras and Rho family members exert their effectson tumorigenesis and on neuronal development and associated disorders, including mental retardation and autism.

We have utilized several model systems to gain insights into the roles of these GTPases and their regulators and effectors. For example, using Drosophila, wedemonstrated a role for Rap1 and its effector Canoe/AF-6 in the regulation of epithelial cell shape changes and cell adhesion, pivotal events governing tumor progression and wound healing processes. Using knockout mice we provided evidence for a role of the Ras-GAP associated protein, Dok-1, in the negative regulation of mitogenic and p210bcr-abl signaling and leukemogenesis. Our studies have also provided insights into how perturbations in Ras and hosignaling canimpact neuronal development and function.  For instance, we found that Ras and Rap GTPases play indispensable roles in activity dependent synaptic plasticity. Furthermore, we demonstrated key roles for Rho regulators in the genesis and polarization of neurons.  Finally, my lab showed that oligophrenin-1, a Rho-GAP involved in X-linked mental retardation, is required for activity-dependent maturation and plasticity of synapses.

 

Selected Publications

Nadif Kasri, N., Nakano-Kobayashi, A., Malinow, R., Li, B., and Van Aelst. L. 2009. The Rho-linked mental retardationprotein oligophrenin-1 controls synapse maturation and plasticity by stabilizing AMPA receptors.Genes Dev. 23: 1289­–1302.

Watabe-Uchida, M., John, K., Janas, J.A., Newey, S.E., and Van Aelst L. 2006. The Rac activator DOCK7 regulates neuronal polarity through local phosphorylation of stathmin/Op18. Neuron 51: 727–739.

Zhao, M., Janas, J.A., Niki, M., Pandolfi, P.P., and Van Aelst, L. 2006. Dok-1 independently attenuates Ras/mitogen-activated protein kinase and Src/c-myc pathways to inhibit platelet-derived growth factor-induced mitogenesis. Mol. Cell. Biol. 26: 2479–2489.

Govek, E.-E., Newey, S.E., and Van Aelst, L. 2005. The role of the Rho GTPases in neuronal development. Genes Dev. 19: 1–49.

Govek, E.-E., Newey, S.E., Akerman, C.J., Cross, J.R., Van der Veken, L., and Van Aelst, L. 2004. The X-linked mental retardation protein oligophrenin-1 is required for dendritic spine morphogenesis. Nat. Neurosci. 7: 364–372.