Hee Jung Chung


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

Mail to:
407 South Goodwin Avenue,
524 Burrill Hall,
Urbana, IL 61801
Lab Page

Hee Jung Chung

Assistant Professor, Molecular & Integrative Physiology
B.A. 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

Currently Teaching

NEUR 590 - Indiv Topics Neuroscience
NEUR 599 - Thesis Research

Mechanisms of Homeostatic Plasticity and Epilepsy

My lab is actively investigating pathogenic mechanisms of epilepsy with specific focuses on ion channel regulation and neural plasticity.

Epilepsy is a common neurological disorder that strikes about 1% of the world population. It is caused by excessive neuronal activity characterized by seizures, which are abnormal and uncontrolled discharges of action potentials. There are growing numbers of new cases of pediatric epilepsy, drug-resistant epilepsy, and other neurologic diseases that have epilepsy as comorbid conditions. Hence, better understanding the pathogensis of epilepsy is in critical need for the development of new therapeutic intervention and remediation of psychomotor retardation associated with this disease.

40% of all epilepsy is mostly caused by mutations in ion channels, which generate electrical current by mediating the movement of ions across the plasma membrane. Since ion channels are essential for generation and modulation of action potentials and synaptic transmission, we investigate how novel epilepsy-associated mutations disrupt their biophysical properties and localization, and ultimately contribute to epilepsy by affecting action potentials and synaptic transmission. Specifically, we focus on KCNQ channels (Chung HJ et al., 2006; Chung HJ, 2014; Cavaretta et al., 2014). They potently inhibit repetitive firing of action potentials, whereas mutations in their subunits lead to benign familial neonatal convulsions (BFNC), myokymia, or severe-symptomatic drug-resistant epileptic encephalopathy.

60% of all epilepsy is caused by non-genetic factors and often associated with initial insults into the brain including traumatic brain injuries (which leads to chronic neuronal inactivity) or status epilepticus (extreme neuronal activity). After certain latency period, these insult-induced chronic activity changes ultimately lead to persistent neuronal hyperexcitability. This process is hypothesized to be caused by the failure of “homeostatic plasticity”, dynamic regulatory mechanisms by which neurons maintain their action potential firing and synaptic strength within physiological limit in response to constant destabilizing changes in neuronal activity. However, the molecular basis of this important plasticity has yet to be elucidated. We investigate the cellular and molecular mechanisms underlying homeostatic plasticity (Lee and Chung, 2014; Lee and Royston et al., 2015; Jang and Royston et al., 2015).

We employ interdisciplinary approaches including primary neuronal culture, live and fixed microscopy, biochemistry, and electrophysiology. In particular, we have identified hundreds of interesting genes whose expression levels are altered during induction of homeostatic plasticity (Lee and Royston et al., 2015), and hence they are all candidate molecular players for homeostatic plasticity, which we would like to pursue. We are also developing mouse models in which neuronal activity can be chronically blocked or activated, and hope to use these models with knock-out mice to understand the role of homeostatic plasticity in epilepsy.

For more information, please visit our lab website https://mcb.illinois.edu/chunghj/

Collaborative Projects

1. Collaboration with Dr. Paul Selvin (Dept of Physics, University of Illinois at Urbana Champaign)

My labs has an on-going collaboration with Dr. Selvin, who is the leading expert of super-resolution imaging techniques. Decades of studies have revealed that activity-dependent changes in the synaptic abundance of glutamate receptors mediate postsynaptic expression of synaptic plasticity. However, imaging the receptor trafficking in and out of synapses is very challenging due to the small size of the synapse (10-40 nm) that is below the resolution limit of light microscopy (~200 nm). Dr. Selvin's group and Dr. Smith's group (Dept of Bioengineering, University of Illinois at Urbana Champaign) has generated a new series of quantum dots with highly compact sizes between 7-10 nm and without nonspecific interactions (sQDs). Our collaboration in cultured hippocampal neurons has demonstrated that sQDs can be used to image AMPA receptors inside synapses of cultured neurons at super-resolution with ~10-20 nm accuracy. While conventional QDs have only a ~15% probability of labeling synaptic AMPARs, ours have a ~85% chance (Cai et al., 2014; Wang et al., 2014)

2. Collaboration with Dr. Paul Lombroso (Dept of Neurobiology and of Psychiatry, Yale University School of Medicine)

My lab has an on-going collaboration with Dr. Lombroso, who first discovered striatal-enriched protein tyrosine phosphatase (STEP) and is the leading investigator for the regulation and roles of STEP in neural plasticity and neuropsychiatric diseases. My lab has identified STEP mRNA and protein level to be altered during homeostatic plasticity. Using Dr. Lombroso's STEP activators and inhibitors, we showed that STEP play important roles in mediating homeostatic scaling of excitatory synaptic strength by regulating dephosphorylation of its substrates, AMPA and NMDA receptors (Jang et al, 2015).

Research Areas

Major Grants

Ongoing Research Funding

1. RO1 NS083402 from National Institute of Health, National Institute of Neurological Disorders and Stroke (2015-2020). Chung (PI)

2. The ICR start-up fund from the University of Illinois at Urbana-Champaign. Chung (PI)

Past Research Funding

1. Basil O’Connor Starter Scholar Research Award, March of Dimes Foundation (2011-2013). Chung (PI)

2. Young Investigator Award, Roy J. Carver Charitable Trust (2011-2014). Chung (PI)

3. Targeted Research Initiative for Severe Symptomatic Epilepsies Grant Award, Epilepsy Foundation (2013-2014). Chung (PI)

Representative Publications

Jang S and Chung HJ (2016). Emerging Link between Alzheimer’s Disease and Homeostatic Synaptic Plasticity. Neural Plasticity. Under revision.

Jang S*, Royston SE*, and Chung HJ (2015). Seizure-induced regulations of amyloid-beta, STEP61, and STEP61 substrates involved in hippocampal synaptic plasticity. Neural Plasticity. Submitted

Jang S*, Royston SE*, Xu J, Cavaretta JP, Vest MO, Lee KY, Lee S, Jeong H, Lombroso PJ, and Chung HJ (2015). Regulation of STEP61 and tyrosine-phosphorylation of NMDA and AMPA receptors during homeostatic synaptic plasticity. Molecular Brain. Sep 22;8(1):55.

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.

Cai E, Ge P, Lee SH, Jeyifous O, Wang Y, Liu Y, Wilson KM, Lim SJ, Baird MA, Stone JE, Lee KY, Davidson MW, Chung HJ, Schulten K, Smith AM, Green WN, 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 10.1016/j.neuroscience.2014.07.038.

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.

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.