Hyunglok Chung

Hyunglok Chung, PhD

Assistant Professor of Neurology, Academic Institute
Houston Methodist
Weill Cornell Medical College


Biography

Dr. Chung is an accomplished scientist and academic specializing in genetics and neurology. Currently serving as an Assistant Professor of Genetics at the Department of Neurology at Houston Methodist Research Institute, he also holds the position of Director of the Drosophila functional core at Houston Methodist.

During his Ph.D. studies at KAIST (Korea Advanced Institute of Science and Technology), Dr. Chung focused on investigating the mechanisms of action of the tumor suppressor gene Schip1 within the context of the Hippo signaling pathway. This research likely involved examining the role of Schip1 in regulating cell growth, proliferation, and apoptosis, as the Hippo pathway is known to play a crucial role in these processes.

Following his PhD, Dr. Chung pursued postdoctoral training at Baylor College of Medicine. During this time, he shifted his research focus to using the fruit fly (Drosophila) as a model organism to study both rare and common neurological diseases affecting humans. The fruit fly model offers several advantages, including its well-characterized genetic toolkit, short lifespan, and conserved biological pathways, making it a valuable system for studying human diseases.

In recognition of his outstanding contributions to the field of genetics and neurology, Dr. Chung was honored as a Warren Alpert Foundation Distinguished Scholar in 2022. This prestigious award highlights his significant achievements and potential for further groundbreaking research.

Furthermore, Dr. Chung serves as a scientific advisor for the Mitchell & Friends Foundation, a role in which he provides expertise and guidance on scientific matters related to Mitchell Syndrome research.

Dr. Chung's ultimate goal is to advance therapeutic approaches for both rare and common neurodegenerative diseases by leveraging the fruit fly model. By studying the underlying genetic and molecular mechanisms of these diseases in flies, he aims to identify potential therapeutic targets and develop novel treatment strategies. This work has the potential to open new avenues for understanding and treating neurodegeneration, ultimately benefiting patients with these debilitating conditions.

Description of Research

Dr. Chung's long-term career focus is to explore the role of lipids in non-neuronal cells and their contribution to neurodegeneration, with a particular emphasis on neuroinflammation. Currently, he is investigating the importance of preserving sphingolipids balance within the nervous system, a key element in preventing neurodegeneration and synaptic dysfunction.

His recent studies on Drosophila have revealed the combined effect of increased levels of Ceramides and sphingosine-1-phosphate (S1P) in glia and hemocytes (fly immune cells). These increased levels trigger the activation of the NF-?B pathway within the nervous system, an event that precedes cell death. Dr. Chung is keen to further explore these lipids within glia and hemocytes, hoping to uncover the molecular mechanisms behind various neurodegenerative diseases.

Additionally, Dr. Chung plans to identify other genes involved in lipid metabolism that play a role in human neurological diseases. Using flies for initial variant assessments, he aims to uncover lipid metabolic genes not yet associated with human disease. His strategy includes collaborations within the Houton Methodist and networking platforms such as GeneMatcher and ModelMatcher. His methods encompass several fly-based strategies to evaluate variant function and gain a deeper understanding of these genes, including humanization strategies facilitated by CRISPR-Cas9.

High-priority genes without existing mouse models will be targeted for mouse knockout generation and phenotyping, and human cells will be used to confirm findings when possible and appropriate.

Areas Of Expertise

Neurodegenerative diseases Lipid metabolism Multiple Sclerosis Parkinson's disease Rare diseases Neuroinflammation Alzheimer's disease Functional genomics Drosophila genetics Glia biology Mitchell Syndrome peroxisomal diseases
Publications

Cdk8/CDK19 promotes mitochondrial fission through Drp1 phosphorylation and can phenotypically suppress pink1 deficiency in Drosophila
Liao, JZ, Chung, HL, Shih, C, Wong, KKL, Dutta, D, Nil, Z, Burns, CG, Kanca, O, Park, YJ, Zuo, Z, Marcogliese, PC, Sew, K, Bellen, HJ & Verheyen, EM 2024, , Nature Communications, vol. 15, no. 1, 3326. https://doi.org/10.1038/s41467-024-47623-8

Very-long-chain fatty acids induce glial-derived sphingosine-1-phosphate synthesis, secretion, and neuroinflammation
Chung, HL, Ye, Q, Park, YJ, Zuo, Z, Mok, JW, Kanca, O, Tattikota, SG, Lu, S, Perrimon, N, Lee, HK & Bellen, HJ 2023, , Cell Metabolism, vol. 35, no. 5, pp. 855-874.e5. https://doi.org/10.1016/j.cmet.2023.03.022

The fly homolog of SUPT16H, a gene associated with neurodevelopmental disorders, is required in a cell-autonomous fashion for cell survival
Ma, M, Zhang, X, Zheng, Y, Lu, S, Pan, X, Mao, X, Pan, H, Chung, HL, Wang, H, Guo, H & Bellen, HJ 2023, , Human Molecular Genetics, vol. 32, no. 6, pp. 984-997. https://doi.org/10.1093/hmg/ddac259

De novo variants in EMC1 lead to neurodevelopmental delay and cerebellar degeneration and affect glial function in Drosophila
Chung, HL, Rump, P, Lu, D, Glassford, MR, Mok, JW, Fatih, J, Basal, A, Marcogliese, PC, Kanca, O, Rapp, M, Fock, JM, Kamsteeg, EJ, Lupski, JR, Larson, A, Haninbal, MC, Bellen, H & Harel, T 2022, , Human Molecular Genetics, vol. 31, no. 19, pp. 3231-3244. https://doi.org/10.1093/hmg/ddac053

De novo FZR1 loss-of-function variants cause developmental and epileptic encephalopathies
Manivannan, SN, Roovers, J, Smal, N, Myers, CT, Turkdogan, D, Roelens, F, Kanca, O, Chung, HL, Scholz, T, Hermann, K, Bierhals, T, Caglayan, HS, Stamberger, H, Craiu, D, Davila, C, Helbig, I, Guerrini, R, Lehesjoki, AE, Marini, C, Muhle, H, Møller, RS, Neubauer, B, Pal, D, Sterbova, K, Striano, P, Talvik, T, Von Spiczak, S, Weber, Y, Hoffman-Zacharska, D, Mefford, H, De Jonghe, P, Yamamoto, S, Weckhuysen, S & Bellen, HJ 2022, , Brain, vol. 145, no. 5, pp. 1684-1697. https://doi.org/10.1093/brain/awab409

Loss-of-function variants in TIAM1 are associated with developmental delay, intellectual disability, and seizures
Lu, S, Hernan, R, Marcogliese, PC, Huang, Y, Gertler, TS, Akcaboy, M, Liu, S, Chung, HL, Pan, X, Sun, X, Oguz, MM, Oztoprak, U, de Baaij, JHF, Ivanisevic, J, McGinnis, E, Guillen Sacoto, MJ, Chung, WK & Bellen, HJ 2022, , American Journal of Human Genetics, vol. 109, no. 4, pp. 571-586. https://doi.org/10.1016/j.ajhg.2022.01.020

Drosophila functional screening of de novo variants in autism uncovers damaging variants and facilitates discovery of rare neurodevelopmental diseases
Marcogliese, PC, Deal, SL, Andrews, J, Harnish, JM, Bhavana, VH, Graves, HK, Jangam, S, Luo, X, Liu, N, Bei, D, Chao, YH, Hull, B, Lee, PT, Pan, H, Bhadane, P, Huang, MC, Longley, CM, Chao, HT, Chung, HL, Haelterman, NA, Kanca, O, Manivannan, SN, Rossetti, LZ, German, RJ, Gerard, A, Schwaibold, EMC, Fehr, S, Guerrini, R, Vetro, A, England, E, Murali, CN, Barakat, TS, van Dooren, MF, Wilke, M, van Slegtenhorst, M, Lesca, G, Sabatier, I, Chatron, N, Brownstein, CA, Madden, JA, Agrawal, PB, Keren, B, Courtin, T, Perrin, L, Brugger, M, Roser, T, Leiz, S, Mau-Them, FT, Delanne, J, Sukarova-Angelovska, E, Trajkova, S, Rosenhahn, E, Strehlow, V, Platzer, K, Keller, R, Pavinato, L, Brusco, A, Rosenfeld, JA, Marom, R, Wangler, MF & Yamamoto, S 2022, , Cell Reports, vol. 38, no. 11, 110517. https://doi.org/10.1016/j.celrep.2022.110517

Loss of IRF2BPL impairs neuronal maintenance through excess Wnt signaling
Undiagnosed Diseases Network 2022, , Science advances, vol. 8, no. 3, eabl5613. https://doi.org/10.1126/sciadv.abl5613

ABCD1 and X-linked adrenoleukodystrophy: A disease with a markedly variable phenotype showing conserved neurobiology in animal models
Manor, J, Chung, H, Bhagwat, PK & Wangler, MF 2021, , Journal of Neuroscience Research, vol. 99, no. 12, pp. 3170-3181. https://doi.org/10.1002/jnr.24953

Phosphatidylserine synthase plays an essential role in glia and affects development, as well as the maintenance of neuronal function
Park, YJ, Kim, S, Shim, HP, Park, JH, Lee, G, Kim, TY, Jo, MC, Kwon, AY, Lee, M, Lee, S, Yeo, J, Chung, HL, Bellen, HJ, Kwon, SH & Jeon, SH 2021, , iScience, vol. 24, no. 8, 102899. https://doi.org/10.1016/j.isci.2021.102899

Loss- or Gain-of-Function Mutations in ACOX1 Cause Axonal Loss via Different Mechanisms
Members of Undiagnosed Diseases Network 2020, , Neuron, vol. 106, no. 4, pp. 589-606.e6. https://doi.org/10.1016/j.neuron.2020.02.021

De Novo Variants in CDK19 Are Associated with a Syndrome Involving Intellectual Disability and Epileptic Encephalopathy
Undiagnosed Diseases Network 2020, , American Journal of Human Genetics, vol. 106, no. 5, pp. 717-725. https://doi.org/10.1016/j.ajhg.2020.04.001

Mutations in ANKLE2, a ZIKA Virus Target, Disrupt an Asymmetric Cell Division Pathway in Drosophila Neuroblasts to Cause Microcephaly
Link, N, Chung, H, Jolly, A, Withers, M, Tepe, B, Arenkiel, BR, Shah, PS, Krogan, NJ, Aydin, H, Geckinli, BB, Tos, T, Isikay, S, Tuysuz, B, Mochida, GH, Thomas, AX, Clark, RD, Mirzaa, GM, Lupski, JR & Bellen, HJ 2019, , Developmental Cell, vol. 51, no. 6, pp. 713-729.e6. https://doi.org/10.1016/j.devcel.2019.10.009

Bi-allelic Variants in IQSEC1 Cause Intellectual Disability, Developmental Delay, and Short Stature
Ansar, M, Chung, HL, Al-Otaibi, A, Elagabani, MN, Ravenscroft, TA, Paracha, SA, Scholz, R, Abdel Magid, T, Sarwar, MT, Shah, SF, Qaisar, AA, Makrythanasis, P, Marcogliese, PC, Kamsteeg, EJ, Falconnet, E, Ranza, E, Santoni, FA, Aldhalaan, H, Al-Asmari, A, Faqeih, EA, Ahmed, J, Kornau, HC, Bellen, HJ & Antonarakis, SE 2019, , American Journal of Human Genetics, vol. 105, no. 5, pp. 907-920. https://doi.org/10.1016/j.ajhg.2019.09.013

An efficient CRISPR-based strategy to insert small and large fragments of DNA using short homology arms
Kanca, O, Zirin, J, Garcia-Marques, J, Knight, SM, Yang-Zhou, D, Amador, G, Chung, H, Zuo, Z, Ma, L, He, Y, Lin, WW, Fang, Y, Ge, M, Yamamoto, S, Schulze, KL, Hu, Y, Spradling, AC, Mohr, SE, Perrimon, N & Bellen, HJ 2019, , eLife, vol. 8, e51539. https://doi.org/10.7554/eLife.51539

Bi-allelic Loss-of-Function Variants in DNMBP Cause Infantile Cataracts
Ansar, M, Chung, HL, Taylor, RL, Nazir, A, Imtiaz, S, Sarwar, MT, Manousopoulou, A, Makrythanasis, P, Saeed, S, Falconnet, E, Guipponi, M, Pournaras, CJ, Ansari, MA, Ranza, E, Santoni, FA, Ahmed, J, Shah, I, Gul, K, Black, GCM, Bellen, HJ & Antonarakis, SE 2018, , American Journal of Human Genetics, vol. 103, no. 4, pp. 568-578. https://doi.org/10.1016/j.ajhg.2018.09.004

Erratum: IRF2BPL Is Associated with Neurological Phenotypes (The American Journal of Human Genetics (2018) 103(2) (245–260), (S0002929718302337) (10.1016/j.ajhg.2018.07.006))
Program for Undiagnosed Diseases (UD-PrOZA) & Undiagnosed Diseases Network 2018, , American Journal of Human Genetics, vol. 103, no. 3, pp. 456. https://doi.org/10.1016/j.ajhg.2018.08.010

IRF2BPL Is Associated with Neurological Phenotypes
Program for Undiagnosed Diseases (UD-PrOZA) & Undiagnosed Diseases Network 2018, , American Journal of Human Genetics, vol. 103, no. 2, pp. 245-260. https://doi.org/10.1016/j.ajhg.2018.07.006

Visual impairment and progressive phthisis bulbi caused by recessive pathogenic variant in MARK3
Ansar, M, Chung, H, Waryah, YM, Makrythanasis, P, Falconnet, E, Rao, AR, Guipponi, M, Narsani, AK, Fingerhut, R, Santoni, FA, Ranza, E, Waryah, AM, Bellen, HJ & Antonarakis, SE 2018, , Human Molecular Genetics, vol. 27, no. 15, pp. 2703-2711. https://doi.org/10.1093/hmg/ddy180

Schip1, a new upstream regulator of Hippo signaling
Chung, HL & Choi, KW 2016, , Cell Cycle, vol. 15, no. 16, pp. 2097-2098. https://doi.org/10.1080/15384101.2016.1191252

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