email vanaelst@cshl.edu, phone (516) 367-6829, fax (516) 367-8815

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 cell growth control, differentiation and morphogenesis. Alterations that affect normal Ras and Rho function result in the development of several diseases including cancer and neuropathologies. Our efforts are centered on defining the role and mechanisms by which Ras and Rho family members exert their effects on tumorigenesis and on neuronal development.

We have utilized several model systems to gain insights into the roles of these GTPases and their regulators and effectors. For example, using Drosophila, we demonstrated 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 p210^bcr-abl signaling and leukemogenesis. Our studies have also provided insights into how perturbations in Ras and Rho signaling can impact neuronal development and function. In collaboration with Dr. Malinow’s lab we found that Ras and Rap GTPases play indispensable roles in activity-dependent synaptic plasticity. Furthermore, we demonstrated that different Rho GTPases serve distinct roles in dendritic arbor and spine development of CA1 neurons in rat hippocampal slices. Finally, my lab recently showed that oligophrenin-1, a Rho-GAP involved in nonsyndromic X-linked mental retardation, is required for normal dendritic spine morphology.

Selected Publications