Linda Van Aelst
Ph.D., Catholic University of Leuven, 1991
Signal transduction; Ras and Rho proteins; tumorigenesis; neuronal development and disorders
Research in my laboratory 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 cell growth control, differentiation and morphogenesis. Alterations in Ras and Rho functions have been causally linked to cancer and cognitive disorders, such as mental retardation, autism and schizophrenia. Our interests lie in understanding how defects in particular Ras- and Rho-linked proteins contribute to these conditions and disorders. Towards this end, efforts in my laboratory are centered on defining their physiological roles in models of cancer (including lung and brain) and neurodevelopmental disorders.
Over recent years we have concentrated in particular on the characterization of distinctive Rho regulators in neurodevelopment and disease. These regulators were identified by us in biochemical and/or genetic screens and, significantly, were subsequently linked to neurological and/or mental disorders. To address their cellular and molecular functions, we use a combination of approaches, including gene transfer into the developing rodent embryo nervous system in situ, electrophysiology, two-photon/confocal imaging, biochemical, and molecular genetic techniques. Our studies have already established vital roles for several Rho regulators in fundamental aspects of neuronal development and function.
Yang, Y.T., Wang, C.L., and Van Aelst, L. 2012. DOCK7 interacts with TACC3 to regulate interkinetic nuclear migration and genesis of neurons from cortical neural progenitors. Nat. Neurosci. 15: 1201–1210.
Nadif Kasri, N., Nakano-Kobayashi, A., and Van Aelst L. 2011. Rapid synthesis of X-linked mental retardation protein OPHN-1 mediates mGluR-dependent LTD through interaction with the endocytic machinery. Neuron 72: 300–315.
Janas, J.A., and Van Aelst, L. 2011. Oncogenic tyrosine kinases target Dok-1 for ubiquitin-mediated proteasomal degradation to promote cell transformation. Mol. Cell Biol. 31: 2552–2565.
Nadif Kasri, N., Nakano-Kobayashi, A., Malinow, R., Li, B., and Van Aelst, L. 2009. The Rho-linked mental retardation protein 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.