Highlighting Illinois researchers in clinical and translational neuroscience with unique approaches to improving neurological function and brain health
The vibrant, diverse neuroscience community at Illinois is working to find solutions to some of today’s most pressing societal health challenges in fields including aging; learning, memory and plasticity; nutrition and cognition; neuroengineering; neuro-and socio-genomics; bioinformatics; and more. More than 300 faculty and staff on the Urbana-Champaign campus identify as researchers in the neuroscience space—regardless of their home department affiliation. These researchers are using leading-edge imaging tools, pioneering studies that progress from the lab to clinical applications with the goal of improving the health and lives of people everywhere.
Hee Jung Chung, PhD
Associate Professor, Molecular and Integrative Physiology
Professor Chung's research interests focus on epilepsy, a brain disorder that affects millions of people worldwide. She is specifically interested in how neurons change to effect an epileptic brain.
Q: Explain your research in neuroscience; what are you investigating?
Epilepsy is a common chronic brain disorder that affects 50 million people of all ages around the world. It is caused by excessive neuronal activity leading to abnormal, uncontrolled, and hypersynchronous discharges of action potentials (AP), which manifest clinically as recurrent unprovoked seizures. About 40% of epilepsy is associated with genetic mutations and occurs as early as infancy. The cause for the rest of epilepsy, including adult onset epilepsy, is unclear. Further, one-third of patients with epilepsy have drug-refractory seizures that have severe consequences including cognitive decline, high mortality rate, and brain damage caused by surgical resection of seizure foci. Therefore, there is a critical need to understand the pathogenesis of epilepsy and develop novel therapeutic interventions with different modes of mechanistic actions.
A fundamental question is, “how does a neuron change itself to produce excessive electrical signals in an epileptic brain compared to a normal brain?”
To address this important question, my laboratory investigates molecular and cellular mechanisms underlying epilepsy with specific focuses on ion channels that are critical regulators of neuronal activity.
Q: How are you currently conducting your research?
The major long-term goals of my research have been to (1) understand how pathogenic variants affect ion channel function and lead to inherited or de novo epilepsy which accompanies neurodevelopmental delay and autism, and (2) identify how neurons persistently alter ion channel function and expression to cause network hyperexcitability in the brain during the development of acquired epilepsy.
To investigate these two areas, my laboratory uses interdisciplinary approaches including mutagenesis, primary hippocampal culture, live and fixed microscopy, biochemistry, electrophysiology, and conditional knock-out and knock-in mouse models.
We focus on the role of neuronal KCNQ/Kv7 potassium channels composed of KCNQ2/Kv7.2 and KCNQ3/Kv7.3 in these two research areas because their voltage-dependent potassium currents potently suppress neuronal excitability. Importantly, dominant mutations in these subunits cause epilepsy including mild symptomatic Benign Familial Neonatal Epilepsy (BFNE) and severe symptomatic Epileptic Encephalopathy (EE). Our rigorous functional analyses of selected Kv7 variants offer fundamental insights into pathogenetic mechanisms underlying Kv7 epilepsy variants (Cavaretta et al, 2014; Kim et al., 2018; Zhang J et al., in preparation). Such genotype-phenotype correlation may prove useful for predicting the nature of channel disruption by novel mutations, and developing personalized treatments for Kv7-associated epilepsy based on patient genotype.
Q: How does being part of the broader Illinois research community support and enhance your work?
It is truly wonderful to be part of the broader Illinois research community. My home department, Molecular and Integrative Physiology (MIP), is part of the School of Molecular and Cellular Biology (MCB). The research environment in MIP and MCB is excellent and stimulating. In addition, I am an affiliate faculty member to Beckman Institute and Carle Hospital. Such a collegial environment supports intellectual and scientific exchange and collaboration. For example, we have been actively collaborating with other investigators in MCB, Beckman, and Carle Hospital. Through our fruitful collaboration with Dr. Eric Bolton (Dept of MIP) and Erik Procko (Dept of Biochemistry), we were able to use novel statistical algorithms and modeling of Kv7.2 structure and identified epilepsy mutation hotspots in key functional protein domains of Kv7.2 and Kv7.3 subunits (Zhang J et al., in preparation).
My collaboration with Dr. Graham Huesmann, a neurologist in Carle Hospital, has also been valuable. Together with Dr. Huesmann, I have received the Carle Illinois Collaborative Research Seed Grant to investigate the pathogenesis of temporal lobe epilepsy, specifically focusing on hippocampal hyperexcitability and sclerosis. We are excited about our future collaboration to study the epileptogenesis in brain tissues resected from human patients that have drug-refractory seizures.
Q: What led to your interest in this particular area of research?
I have always been fascinated by how neurons produce electrical signals and communicate with each other to execute brain functions, including learning and memory. Importantly, these intrinsic neuronal excitability and communications are altered in multiple neurologic and neuropsychiatric diseases for which we have no cure. My laboratory investigates pathogenic mechanisms underlying de novo variants in potassium channels which lead to early onset epileptic encephalopathy characterized by intractable seizures, severe psychomotor and speech delay, and high risk of mortality. In addition, we investigate the basic mechanisms by which neuronal excitability and communication becomes stronger in health and disease (such as epilepsy). My laboratory’s research on ion channel regulation will not only provide the fundamental insights into how neuronal excitability and communication is regulated under physiologic and pathologic conditions. This is exciting and important. The possibility of our research in helping epilepsy patients with a vast array of comorbidity is a huge motivation for all of us in my laboratory.
Q: In what ways to you envision your work improving society or reaching people?
Epilepsy is the second most prominent neurological disease. Seizures occur in patients with different severity and frequency and without warning. Coping with chronic and unpredictable occurrence of seizures as well as variable therapeutic efficacy and side effects of anti-epileptic drugs can all have detrimental effects on patients’ quality of life and their independence in physical activity. In addition to progressive cognitive deficits and increased risk of mortality, patients experience social isolation, reduced self-esteem, and depression.
We envision that any discovery in our research will provide better understanding of the pathogenesis of epilepsy and help develop better therapeutic interventions and early diagnostics for this devastating disease. Importantly, such outcomes will improve epilepsy patients’ quality of life as well as social and behavioral deficits associated with this disease.