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Associate Professor of Pharmacology and Cancer Biology
Duke University School of Medicine
Duke-NUS Graduate Medical School
8 College Road #05-13
Singapore 169857, Singapore
We study the mechanisms underlying the processes of learning and memory, at the molecular, cellular and systems level. Current projects focus on the NMDA receptor and the immediate-early gene Arc, which play essential roles in learning and memory consolidation, respectively. We have shown that efficient Arc translation requires coincident activation of the NMDA receptor and receptors associated with fear/reward pathways, suggesting that Arc mediates a role for emotion in memory consolidation. Our localization of Arc protein to the nucleus, and its association PML bodies, suggests that Arc mediates formation of long term memories through epigenetic regulation of gene expression. A second project investigates how information is processed, encoded and stored in networks formed by neurons growing in vitro, using a combination of optogenetics and multi-electrode array recording techniques. These experiments have demonstrated that cultured neuronal networks have fading and hidden memory processes that are similar to those observed in vivo, and thereforeprovide a novel platform for investigating the molecular and physiological basis of disorders in memory, cognition, and perception. These projects are supported by an in silico drug design program which identifies small molecules with efficacy at therapeutic targets identified by our research program.
Van de Ven TJ, VanDongen HMA and VanDongen AMJ, 2005, The non-kinase phorbol ester receptor alpha1-chimaerin binds the NMDA receptor NR2A subunit and regulates dendritic spine density, J. Neurosci. 25:9488-9496.
Bloomer WAC, VanDongen HMA and VanDongen AMJ, 2007, Activity-regulated cytoskeleton-associated protein Arc/Arg3.1 binds to spectrin and associates with nuclear promyelocytic leukemia (PML) bodies, Brain Res. 1153:20-33.
Bloomer WAC, VanDongen HMA and VanDongen AMJ, 2008, Arc/Arg3.1 translation is controlled by convergent N-methyl-D-aspartate and GS-coupled receptor signaling pathways, J. Biol. Chem. 283:582-592.
Fu Y, Chin LK, Bourouina T, Liu AQ and VanDongen AMJ, 2012, Nuclear deformation during breast cancer cell transmigration, Lab-on-a-Chip 12:3778-90.
Ju H, Xu J-X, Chong E, and VanDongen AMJ, 2013, Effects of synaptic connectivity on Liquid State Machine performance, Neural Networks 38:39-51.
Dranias MR, Ju H, Rajaram E, and VanDongen AMJ, 2013, Short-term memory in networks of dissociated cortical neurons, J. Neurosci. 33:1940-55.
Wee CL, Teo S, Oey NE, Wright GD, VanDongen HMA and VanDongen AMJ, 2014, Nuclear Arc interacts with the histone acetyltransferase Tip60 to modify H4K12 acetylation, eNeuro 0019-14.2014.
Oey NE, Leung, H-W, Ezhilarasan E, Zhou L, Beuerman RW, VanDongen HMA, and VanDongen AMJ, 2015, A neuronal activity-dependent dual function chromatin-modifying complex regulates Arc expression, eNeuro 0020-14.2015.
Dranias MR, Westover MB, Cash S, VanDongen AMJ, 2015, Stimulus information stored in lasting active and hidden network states is destroyed by network bursts, Front. Intergr. Neurosci. 9:14.
Ju H, Dranias MR, Banumurthy G, and VanDongen AMJ, 2015, Spatio-temporal memory is an intrinsic property of networks of dissociated cortical neurons, J. Neurosci. 35:4040-51.