About

Hee Jung Chung is a Professor in the Departments of Molecular and Integrative Physiology and Neuroscience Program, as well as at the Beckman Institute for Advanced Science and Technology at the University of Illinois at Urbana-Champaign. She earned her B.S. from Cornell University in 1995 and her Ph.D. from Johns Hopkins University School of Medicine in 2002, followed by postdoctoral training at the University of California, San Francisco from 2002 to 2009. Her research program focuses on understanding the mechanisms underlying homeostatic plasticity and epilepsy, with a particular emphasis on how ion channel function and localization contribute to neuronal excitability and disease. Her lab investigates the role of KCNQ/Kv7 potassium channels, which are critical in preventing repetitive and burst firing of action potentials and are implicated in various forms of epilepsy, intellectual disability, and autism. Chung's research aims to elucidate how mutations in these channels disrupt their function and neuronal distribution, leading to hyperexcitability and epilepsy. Additionally, her group studies the molecular mechanisms that establish and regulate the polarized localization of Kv7 channels in axons, which is essential for normal neuronal function. These studies have provided significant insights into epilepsy mutations and axonal targeting of Kv7 channels, contributing to the development of potential therapeutic strategies. Another major focus of her research is homeostatic plasticity, the ability of neurons to adapt their electrical activity in response to changes in neuronal activity or sensory experience. Chung's laboratory has identified signaling pathways and molecular players involved in homeostatic control of intrinsic excitability, distinct from synaptic scaling, through studies in cultured hippocampal neurons. Her work has revealed genes and proteins, such as potassium channels and striatal-enriched protein tyrosine phosphatase (STEP61), that regulate excitability and synaptic strength during homeostatic plasticity. Current research interests include the function and regulation of axonal Kv7 channels in hippocampal circuits, the role of STEP61 in epilepsy and Alzheimer's disease pathogenesis, and the development of novel transgenic mouse models to study homeostatic plasticity in vivo.

Research topics

• Computer Science
• Biology
• Materials science
• Neuroscience
• Chemistry
• Nanotechnology
• Internal medicine
• Medicine
• Endocrinology
• Biophysics
• Cell biology
• Artificial Intelligence
• Physics
• Biochemistry
• Embedded system
• Computer hardware
• Optics
• Distributed computing
• Computer architecture
• Genetics

Selected publications

• APOE4 reduces hippocampal expression of phosphoglycerate kinase 1 and sodium potassium pump to enhance seizure susceptibility in mice

  Neurobiology of Disease · 2025-12-24 · 1 citations

  articleOpen accessSenior authorCorresponding

  Alzheimer's disease (AD) is the leading cause of dementia, characterized by the deposition of amyloid-β plaques and neurofibrillary tangles composed of hyperphosphorylated tau. Seizures have also emerged as a prevalent clinical feature of AD and are associated with APOE4 , the major genetic risk factor of AD. However, the mechanism by which APOE4 induces seizures and neuronal hyperexcitability is incompletely understood. We discovered that human APOE4 targeted replacement mice showed increased seizure severity and seizure-induced death at 5.5–7 but not 2–3 months of age compared to APOE3 mice using the kainic acid model of status epilepticus which preferentially arises from the hippocampus. While Tau burden alone did not alter seizure susceptibility in mice, APOE4 together with Tau burden enhanced seizure severity in female mice. Notably, APOE4 was associated with decreased hippocampal levels of sodium/potassium-ATPase, ATP-generating glycolytic enzymes, including phosphoglycerate kinase 1 (PGK1) and pyruvate kinase M, and ATP. While inhibition of Na + /K + - ATPase increased hippocampal neuronal activity, pharmacologically stimulating PGK1 with terazosin increased hippocampal ATP levels and decreased seizure severity in APOE4 but not APOE3 mice. Lastly, co-application of lactate dehydrogenase inhibitor sodium oxamate to prevent the conversion of pyruvate to lactate further enhanced hippocampal ATP levels and suppressed seizure severity in APOE4 mice. Together, these findings suggest that reductions in hippocampal expression of sodium/potassium-ATPase and glycolytic enzymes may underlie APOE4 -associated hippocampal hyperexcitability, revealing a novel mechanistic insight. Our results also demonstrate potent anti-seizure effects of terazosin, supporting the possibility of repurposing this anti-hypertension drug to mitigate seizure comorbidity in AD. • APOE4 increases seizure propensity in mice by 5.5 months of age compared to APOE3. • APOE4 enhances seizure severity in female mice in the presence of tau burden. • APOE4 decreases expression of Na + /K + -ATPase essential for electrochemical gradient. • APOE4 reduces hippocampal levels of ATP and glycolytic enzymes (PGK1 and PKM). • PGK1 activator terazosin increases ATP level and reduces APOE4-associated seizures.

  PublisherDOI

• BPS2025 - Unique spatial dependence of AMPAR subunit clusters revealed through qPAINT

  Biophysical Journal · 2025-02-01

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  PublisherDOI

• BPS2025 - Phosphorylation of Kv7.2 helix B differentially affects calmodulin and PIP2 binding and axonal surface expression and function

  Biophysical Journal · 2025-02-01

  articleSenior author
  PublisherDOI

• BPS2025 - Impact of calmodulin and phosphorylation on Kv7 voltage-gated potassium channels

  Biophysical Journal · 2025-02-01

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  PublisherDOI

• Comparing absolute numbers of Glua1 and Glua2 in hippocampal neurons through qPAINT

  Biophysical Journal · 2024-02-01

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  PublisherDOI

• An emerging role of STriatal-Enriched protein tyrosine Phosphatase in hyperexcitability-associated brain disorders

  Neurobiology of Disease · 2024-08-17 · 4 citations

  reviewOpen accessSenior authorCorresponding

  STriatal-Enriched protein tyrosine Phosphatase (STEP) is a brain-specific tyrosine phosphatase that is associated with numerous neurological and neuropsychiatric disorders. STEP dephosphorylates and inactivates various kinases and phosphatases critical for neuronal function and health including Fyn, Pyk2, ERK1/2, p38, and PTPα. Importantly, STEP dephosphorylates NMDA and AMPA receptors, two major glutamate receptors that mediate fast excitatory synaptic transmission. This STEP-mediated dephosphorylation leads to their internalization and inhibits both Hebbian synaptic potentiation and homeostatic synaptic scaling. Hence, STEP has been widely accepted to weaken excitatory synaptic strength. However, emerging evidence implicates a novel role of STEP in neuronal hyperexcitability and seizure disorders. Genetic deletion and pharmacological blockade of STEP reduces seizure susceptibility in acute seizure mouse models and audiogenic seizures in a mouse model of Fragile X syndrome. Pharmacologic inhibition of STEP also decreases hippocampal activity and neuronal intrinsic excitability. Here, we will highlight the divergent roles of STEP in excitatory synaptic transmission and neuronal intrinsic excitability, present the potential underlying mechanisms, and discuss their impact on STEP-associated neurologic and neuropsychiatric disorders.

  PublisherDOI

• Neuronal innervation regulates the secretion of neurotrophic myokines and exosomes from skeletal muscle

  Proceedings of the National Academy of Sciences · 2024 · 36 citations

  • Biology
  • Internal medicine
  • Neuroscience

  Myokines and exosomes, originating from skeletal muscle, are shown to play a significant role in maintaining brain homeostasis. While exercise has been reported to promote muscle secretion, little is known about the effects of neuronal innervation and activity on the yield and molecular composition of biologically active molecules from muscle. As neuromuscular diseases and disabilities associated with denervation impact muscle metabolism, we hypothesize that neuronal innervation and firing may play a pivotal role in regulating secretion activities of skeletal muscles. We examined this hypothesis using an engineered neuromuscular tissue model consisting of skeletal muscles innervated by motor neurons. The innervated muscles displayed elevated expression of mRNAs encoding neurotrophic myokines, such as interleukin-6, brain-derived neurotrophic factor, and FDNC5, as well as the mRNA of peroxisome-proliferator-activated receptor γ coactivator 1α, a key regulator of muscle metabolism. Upon glutamate stimulation, the innervated muscles secreted higher levels of irisin and exosomes containing more diverse neurotrophic microRNAs than neuron-free muscles. Consequently, biological factors secreted by innervated muscles enhanced branching, axonal transport, and, ultimately, spontaneous network activities of primary hippocampal neurons in vitro. Overall, these results reveal the importance of neuronal innervation in modulating muscle-derived factors that promote neuronal function and suggest that the engineered neuromuscular tissue model holds significant promise as a platform for producing neurotrophic molecules.

  PublisherOA PDFDOI

• Automatic analysis of dendritic spines incorporating machine learning on widefield fluorescent images of thick brain slices

  Biophysical Journal · 2024-02-01

  articleOpen access
  PublisherOA PDFDOI

• Reply to Caruso Bavisotto et al.: Toward exploring the potential of muscle-secreting exosomes in the muscle–brain axis

  Proceedings of the National Academy of Sciences · 2024-12-31 · 1 citations

  articleOpen access
  PublisherOA PDFDOI

• Revealing synaptic nanostructure distribution through automatic dendritic spine segmentation and single-molecule localization microscopy

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-07-18 · 3 citations

  preprintOpen access

  Relating dendritic spine morphology to synaptic organization in brain tissue is essential for understanding excitatory synaptic transmission and plasticity. Single-molecule localization microscopy (SMLM) offers the spatial precision needed to study the synaptic protein distribution at the nanoscale. However, the widefield setup required for SMLM produces diffraction-limited images with poor contrast and resolution in thick brain slices (> 30 μm), making accurate segmentation of dendritic spines challenging. To overcome this challenge, we developed an automated 3D segmentation approach tailored to this condition by combining two existing machine-learning models. We integrated this strategy with SMLM-based localization of synaptic proteins to map post-synaptic protein PSD-95 within spines at nanoscale resolution. This framework, named ISEPLA (Integrated Spine Extraction and Protein Localization Analysis), revealed a hierarchical organization of synaptic proteins: spines contain multiple nanomodules, each composed of smaller nanodomains. Larger spines contain more nanomodules, and larger nanomodules comprise more nanodomains. Therefore, our method enables precise morphological and molecular analysis under physiologically relevant imaging conditions, providing new insights into the synaptic organization in spines.

  PublisherDOI

Recent grants

• Super-Resolution Microscopy of Small Quantum Dots to Elucidate the Mechanisms of Alzheimer's Disease

  NIH · $3.3M · 2016–2022

• Tuning neuronal excitability by axonal targeting of Kv7 channels

  NIH · $1.7M · 2015–2021

• Super-Resolution Microscopy of Neuronal Synapses with Advanced Imaging Tools

  NIH · $3.2M · 2017–2026

Frequent coauthors

• Richard L. Huganir

  Johns Hopkins Medicine

  36 shared

• Kwan Young Lee

  University of Illinois Urbana-Champaign

  18 shared

• Nien‐Pei Tsai

  University of Illinois Urbana-Champaign

  17 shared

• David J. Linden

  Discovery Institute

  15 shared

• Hyunjoon Kong

  University of Illinois Urbana-Champaign

  15 shared

• Jun Xia

  Huaiyin Normal University

  13 shared

• Jiaren Zhang

  Beijing Institute of Petrochemical Technology

  12 shared

• Gregory Tracy

  University of Illinois System

  10 shared

Education

• Ph.D., Neuroscience

  Johns Hopkins Medicine

  2002

• B.A., Biochemistry

  Cornell University

  1995

Awards & honors

• Cornell University-HHMI Undergraduate Research Fellowship (1…
• Paul Ehrlich Young Investigator Award, Johns Hopkins Univers…
• Ruth L. Kirschstein National Research Service Award (2004-20…
• Basil O'Connor Starter Scholar Research Award, March of Dime…
• Carver Young Investigator Competition Award, Roy J. Carver C…