Hee Jung Chung


427A Burrill Hall
Office: (217) 244-6839
Lab: (217) 244-6839
Fax: (217) 333-1133

Mail to: Department of Molecular and Integrative Physiology
524 Burrill Hall
407 South Goodwin Avenue,
Urbana, IL 61801
Lab Page

Hee Jung Chung

Assistant Professor of Molecular and Integrative Physiology


B.S. 1995 Cornell University, Ithaca, NY
Ph.D. 2002 Johns Hopkins University School of Medicine, Baltimore, MD
Postdoc 2002-2009 University of California, San Francisco, CA

Teaching Interests

Activity-dependent regulation of ion channels in Neural Plasticity

Activity-dependent persistent changes in synaptic transmission (synaptic plasticity) as well as action potential/intrinsic excitability (intrinsic plasticity) are thought to provide the cellular basis for information processing and storage in the brain. Abnormal synaptic and intrinsic plasticity have been implicated in many neurological disorders and diseases.

Given that ion channels are essential for neuronal function in generating and modulating synaptic transmission and action potential, the main research goal of my laboratory is to understand how persistent functional changes in ion channels contribute to synaptic and intrinsic plasticity under physiologic and pathologic conditions, and ultimately animal behavior.

Specifically, research in our laboratory centers on dissecting mechanisms for neuronal plasticity and pathogenic mechanisms underlying epilepsy. Current interests include (1) the mechanisms of polarized KCNQ potassium channel trafficking to the axons, and (2) the function and regulation of axonal potassium channels and STEP (STriatal-Enriched tyrosine Phosphatase) in homeostatic plasticity of hippocampal circuits.

To investigate these two areas, my lab uses interdisciplinary approaches including primary neuronal culture, live and fixed microscopy, biochemistry, electrophysiology, and mouse genetics.

(1) What are the mechanisms underlying polarized localization of KCNQ channels?

Highly concentrated in the axons, voltage-gated sodium and potassium channels generate and terminate action potentials, respectively. Neuronal KCNQ potassium channels (also called M-channels) composed of KCNQ2 and KCNQ3 subunits give rise to slowly activating and non-inactivating voltage-dependent outward K+ current that potently inhibits repetitive firing of action potentials.

Neuronal KCNQ channels have emerged as critical players of epilepsy for two main reasons. First, their specific agonist (ezogabine/retigabine) is an approved anti-epileptic drug. Second, benign familial neonatal convulsions (BFNC) and severe symptomatic drug-resistant epileptic encephalopathy are associated with mutations in KCNQ channel subunits, KCNQ2 and KCNQ3. These epilepsy mutations cause 20-25% reduction in current expression in heterologous systems. In hippocampal neurons, we have shown that BFNC mutations disrupt enrichment of KCNQ channels at the axonal surface, including axonal initial segment, the critical site for action potential initiation and modulation (Chung et al., 2006; Cavaretta et al., 2014).

We are actively investigating how mutations of KCNQ channels associated with epileptic encephalopathy disrupt their functions and neuronal distribution, ultimately leading to neuronal hyperexcitability and epilepsy. Since the fundamental function of a neuron depends critically on precise localization and density of these channels, we also study the mechanisms by which polarized distribution of KCNQ channels in axons or dendrites is established, maintained, and regulated. Understanding these fundamental physiologic and pathologic mechanisms involving KCNQ channel trafficking will help us develop therapeutic strategy to reverse the effects of epilepsy mutations.

(2) What are the molecular mechanisms underlying homeostatic plasticity?

Homeostatic plasticity encompasses dynamic regulatory mechanisms by which neurons maintain their action potential firing rates and synaptic strength within physiological limits. While the failure of this plasticity likely contributes to the pathogenesis of hyperexcitability-associated disorders including epilepsy, the molecular basis of this important plasticity has yet to be elucidated.

We have shown that hippocampal neurons employ NMDA receptors as activity sensor to mediate homeostatic intrinsic plasticity in response to chronic activity blockade (Lee KY and Chung HJ, 2014). Recently, homeostatic synaptic plasticity has been shown to require transcription, suggesting that regulation of gene expression mediates its induction. From our unbiased gene expression profiling in hippocampal neuronal culture, we identified a number of potassium channels and their modulators that exhibit activity-dependent changes in their mRNA and protein expression, which may likely contribute to the expression of homeostatic plasticity (Lee KY et al., 2015).

One of the potassium channels we have identified is KCNQ channel. We are currently investigating how activity-dependent regulation of KCNQ channels and their modulating proteins is achieved and how such regulation contributes to homeostatic intrinsic plasticity. Given that mutations in KCNQ channels cause benign to severe forms of epilepsy, these studies may lay a firm foundation for exploring regulation of KCNQ gene expression as novel therapeutic strategies for epilepsy.

We have also identified STEP whose expression is altered during homeostatic plasticity. Highly concentrated at the postsynaptic density, STEP is shown to oppose synaptic strength by dephosphorylating AMPA and NMDA receptors and promoting their internalization. We are currently investigating the extent to which activity-regulated STEP contributes to homeostatic synaptic plasticity. These studies will provide novel mechanistic and functional insights into how neurons fine-tune their synaptic homeostasis. Since dysregulation of STEP is implicated in epilepsy as well as multiple neurologic diseases that cause lasting cognitive and psychiatric impairments, these studies may lay a firm foundation for exploring STEP as novel therapeutic targets for multiple neurologic diseases.


The Cornell University-HHMI Undergraduate Research Fellowship. 1994
Paul Ehrlich Young Investigator Award, Johns Hopkins University School of Medicine, 2002
Ruth L. Kirschstein National Research Service Award, 2004-2007
Basil O'Connor Starter Scholar Research Award, March of Dimes Foundation, 2/2011 - 1/2013
Young Investigator Award, Roy J. Carver Charitable Trust, 4/2011 - 3/2014
Targeted Research Initiative for Severe Symptomatic Epilepsies Grant Award, Epilepsy Foundation, 7/2013 - 6/2014
James E. Heath Award for excellence in teaching in Physiology from the School of MCB, University of Illinois, 2014

Representative Publications

Jang S*, Royston SE*, Xu J, Vest MO, Lee S,Lee KY, Cavaretta JP, Lombroso P , and Chung HJ (2015). Chronic enhancement of network activity upregulates STEP61 and downregulates tyrosine-phosphorylation and levels of NMDA and AMPA receptors in hippocampal neurons. In preparation.

Lee K*, Royston SE*, Vest MO, Ley DJ, Lee S, Bolton EC, and Chung H (2015). (*These authors contributed equally). N-methyl-D-aspartate Receptors mediate Activity-dependent Down-Regulation of Potassium Channel Genes during the Expression of Homeostatic Intrinsic Plasticity. Molecular Brain. 8(1):4.

Wang Y, Cai E, Rosenkranz T, Ge P, Teng KW, Lim SJ, Smith A, Chung HJ, Sachs F, Sachs F, Green W, Gottlieb P, and Selvin PR (2014). Small Quantum Dots Conjugated to Nanobodies as Immunofluorescence Probes for Nanometric Microscopy. Bioconjugate Chemistry. 25(12):2205-11.

Wang Y, Cai E, Rosenkranz T, Ge P, Teng KW, Chung HJ, Sachs F, Gottlieb P, and Selvin PR (2014). Stable small quantum dots for synaptic receptor tracking on live neurons. Angewandte Chemie, 53(46):12484-8.

Lee KY and Chung HJ (2014). NMDA receptors and L-type voltage-gated Ca2+ channels mediate the expression of bidirectional homeostatic intrinsic plasticity in cultured hippocampal neurons. Neuroscience, (277):610-23.

Cavaretta JP*, Sherer KS*, Lee KY, Issema RS, Kim EH, and Chung HJ (2014). (*These authors contributed equally). Polarized Axonal Surface Expression of Neuronal KCNQ Potassium Channels is Regulated by Calmodulin Interaction with KCNQ2 Subunit. PLos One, 9(7):e103655. DOI:10.1371/journal.pone.0103655.

Chung HJ (2014). Role of calmodulin in neuronal Kv7/KCNQ potassium channels and epilepsy. Frontiers in Biology. 9(3):205-15.

Vega L JC, Lee MK, Jeong JH, Smith CE, Lee KY, Chung HJ, Leckband DE, Kong H. (2014). Recapitulating cell-cell adhesion using N-Cadherin biologically tethered to substrates. Biomacromolecules 15(6):2172-9.

Hearing M, Kotecki L, Marron Fernandez de Velasco E, Fajardo-Serrano A, Chung HJ, Luján R, Wickman K. (2013). Repeated Cocaine Weakens GABAB-Girk Signaling in Layer 5/6 Pyramidal Neurons in the Prelimbic Cortex. Neuron 80(1):159-70

Chung HJ*, Lee HK* (2009). Constructing a road map from synapses to behaviour. Meeting on Synapses: From Molecules to Circuits & Behavior. (*These authors contributed equally to this work). EMBO Rep.,10(9):958-62. PubMed Central [PMCID2750071]

Chung HJ*, Woo-ping Ge*, Xiang Qian, Ofer Wiser, Jan YN, and Jan LY (2009). G-protein activated inwardly rectifying potassium channels mediate depotentiation of long-term potentitation. (*These authors contributed equally to this work). Proc Natl Acad Sci U S A, 106(2): 635-40.

Chung HJ, Xiang Qian, Melissa Ehlers, Jan YN, and Jan LY (2009). Neuronal activity regulates phosphorylation-dependent surface delivery of G-protein activated inwardly rectifying potassium channels. Proc Natl Acad Sci U S A, 106(2): 629-34.

Chung HJ, Jan YN, and Jan LY (2006). Impaired polarized surface expression of neuronal KCNQ channels as a mechanism for benign familial neonatal convulsion. Proc Natl Acad Sci U S A, 103 (23): 8870-5

Chung HJ, Lau LF, Huang YH and Huganir RL (2004). Regulation of NMDA Receptor complex and trafficking by activity-dependent phosphorylation of NR2B subunit PDZ ligand. J Neurosci, 24(45):10248-59.

Heynen AJ, Yoon BJ, Liu CH, Chung HJ, Huganir RL and Bear MF (2003). Molecular mechanism for loss of visual cortical responsiveness following brief monocular deprivation. Nat Neurosci. 6(8):854-62.

Chung HJ*, Steinberg JP*, Huganir RL, Linden DJ (2003). Requirement of AMPA receptor GluR2 phosphorylation for cerebellar long-term depression. (*These authors contributed equally to this work). Science, 300(5626):1751-5.

McDonald BJ, Chung HJ, and Huganir RL (2001). Identification of Protein Kinase C phosphorylation sites within the AMPA receptor GluR2 subunit. Neuropharmacology, 41(6):672-679

Kim CH*, Chung HJ*, Lee H-K-, and Huganir RL (2001). Interaction of the AMPA receptor subunit GluR2/3 with PDZ domains regulates hippocampal long term-depression. (*These authors contributed equally to this work). Proc Natl Acad Sci U S A, 98(20):11725-30

Xia J, Chung HJ, Wihler C, Huganir RL, and Linden DJ (2000). Cerebellar long-term depression requires PKC-regulated interactions between GluR2/3 and PDZ domain-containing proteins. Neuron, 28(2):499-510.

Chung HJ, Xia J, Scannevin RH, Zhang X, and Huganir RL (2000). Phosphorylation of the AMPA receptor subunit GluR2 differentially regulates its interaction with PDZ domain-containing proteins. J Neurosci, 20(19):7258-67.