Je, H. Shawn

Research Interests:

Synapse structure and function is continuously remodeled during development and throughout life by experience, such as learning new skills or forming new memories. This process, known as synaptic plasticity, is thus critical for normal brain function. In addition, several neurological and neurodegenerative diseases such as schizophrenia and Alzheimer's disease have been correlated with deficits in synaptic plasticity. The Shawn laboratory aims to investigate the molecular and cellular mechanisms for synaptic plasticity using a wide variety of optical, electrophysiological, and molecular techniques.

Developing new molecular techniques and probes for neuroscience research

Recently, we have developed a chemically inducible system that allows rapid and reversible inhibition of protein synthesis in specific cells. In addition, we are currently working on several viral probes that allow us to control neuronal excitability rapidly and reversibly.

Developing a circuit-based mouse model of schizophrenia

Schizophrenia is a devastating disorder. Risk genes and complex neurotransmitter interactions may synergistically act to produce schizophrenia. We hypothesize that interneuron dysfunction in the hippocampal and cortical microcircuit contributes to schizophrenia pathophysiology. In collaboration with Dr. Henry Yin at Duke, we are currently developing and testing our mouse models using novel behavioral paradigms and in vivo multi-electrode recording technique.

Investigating the molecular mechanisms of dendritic spine plasticity

Dendritic spines, micron sized protrusions emanating from the dendritic surface, are major sites of postsynaptic excitation in the mammalian brain. Dendritic spines show rapid motility and plastic morphology during neuronal activity. In addition, spine abnormality and dysfunction have been associated with cognitive disorders including Alzheimer's disease and schizophrenia. We seek to understand the molecular mechanisms of spine plasticity using two-photon-based imaging in combination with electrophysiology.

Selected Publications:

Synaptic dysfunction and abnormal behaviors in mice lacking major isoforms of Shank3. Wang X, McCoy PA, Rodriguiz RM, Pan Y, Je HS, Roberts AC, Kim CJ, Berrios J, Colvin JS, Bousquet-Moore D, Lorenzo I, Wu G, Weinberg RJ, Ehlers MD, Philpot BD, Beaudet AL, Wetsel WC, Jiang YH. Hum Mol Genet. 2011 May 27. In Press

Je, H.S. *, Ji. Y. *, Wang, Y., Yang, F., Wu, W., and Lu, B. (2011) Presynaptic protein synthesis required for NT-3-induced long-term synaptic modulation. Molecular Brain, 4:1. *: co-first authors.

Jiang, Z., Belforte, J., Lu, Y., Yabe, Y., Pickel, J., Smith, C., Je, H.S., Lu, B., and Nakazawa, K. (2010) eIF2a phosphorylation-dependent translation in CA1 pyramidal cells impairs hippocampal memory consolidation without affecting general translation. J. Neurosci.30, 2582-94.

Je, H.S.*, Lu, Y.*, Yang, F., Nagappan, G., Zhou, J., Jiang, Z., Nakazawa, K., and Lu, B. (2009) Chemically Inducible Inactivation of Protein Synthesis in Genetically Targeted Neurons. J. Neurosci. 29, 6761-16. *: co-first authors.

Yang, F.*, Je, H.S.*, Ji, Y., Nagappan, G., Hempstead, B., and Lu, B. (2009) ProBDNF-induced Synaptic Depression and Retraction at Developing Neuromuscular Synapses. J. Cell Biol. 185, 727-41. *: co-first authors.

Highlighted in:

1. BDNF sends mixed signals, J. Cell Biol. (2009) 185:566>
2. Faculty of 1000, 23 Jun 2009. F1000.com/1162040

Lu, Z., Je, H.S., Young, P., Gross, J., Lu, B., and Feng, G. (2007) Regulation of synaptic growth and maturation by a synapse-associated E3 ubiquitin ligase at the neuromuscular junction. J. Cell Biol.18, 1077-89.

Highlighted in: Faculty of 1000 Biology, 9 Aug 2007. F1000.com/1088748

Je, H.S., Yang, F., Zhou, J., and Lu, B. (2006) Neurotrophin 3 induces structural and functional modification of synapses through distinct molecular mechanisms. J Cell Biol. 18, 1029-42.

Je, H.S., Zhou, J., Yang, F., and Lu, B. (2005) Distinct mechanisms for neurotrophin-3-induced acute and long-term synaptic potentiation. J. Neurosci. 14, 11719-29.