Bellen Lab

Hyunglok Chung

Hyunglok Chung

BS, KAIST, Republic of Korea
PhD, KAIST, Republic of Korea (Kwang-Wook Choi)

Research Interests

My ultimate career goal is to elucidate the function of Very long-chain fatty acids (VLCFA, ?22 carbons in length) during development and how they contribute to neuroinflammation and disease. Lipids are critical for neuronal development, synaptic plasticity, and function. Abnormal lipid metabolism contributes to the pathogenesis of several diseases associated with glial dysfunction, such as Alzheimer's disease and Parkinson's disease. Using a genetic model system and collaboration with clinicians, I discovered variants in ACOX1 (Acyl-CoA Oxidase1) in a patient with ataxia, progressive motor loss, and myeloneuropathy. Loss-of-function mutations in Drosophila ACOX1 lead to VLCFA accumulation, reduced lifespan, impaired synaptic transmission, and glial and axonal loss, while gain-of-function causes increased levels of ACOX1 protein and function, resulting in elevated levels of reactive oxygen species in glia in flies and murine Schwann cells. These findings indicate conserved functions of ACOX1, provide compelling evidence that variants in ACOX1 cause glial loss, and establish proof of principle that we can study the pathogenesis of disease with this humanized fly system. Using functional analysis in Drosophila, I discovered the mechanisms underlying ACOX1 deficiency and gain and identified therapeutic avenues for both loss and gain in patients (Chung et al., 2020). My recent data show that glia and immune cells with elevated levels of VLCFA may act synergistically to cause a neuroinflammatory response and that this may serve as a model for Multiple Sclerosis (MS). Therefore, I aim to study VLCFA in glia and immune cells to elucidate the molecular underpinnings of neuroinflammatory diseases.


Publications

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 HJ*, Harel T*  (2022) De novo variants in EMC1 lead to neurodevelopmental delay and cerebellar degeneration and affect glial function in DrosophilaHuman Molecular Genetics : in press. (*equal contribution)  
Lu S, Herman R, Marcogliese, Huang Y, Gertler TS, Akcaboy M, Liu S, Chung HL, Pan X, Sun X, Oguz M, Oztoprak U, deBaaij JHF, Ivanisevic J, McGinnis E, Guillen Sacoto MJ, Chung WK, Bellen HJ (2022) Loss of function variants in TIAM1 are associated with developmental delay, intellectual disability and seizures. AJHG :DOI: 10.1016/j.ajhg.2022.01.020. (*equal contribution) [Abstract]
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, Longley CM, Chao HT, Chung HL, Haelterman NA, Kanca O, Manivannan SN, Rossetti LZ, Gerard A, Schwaibold EMC, 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, Keller R, Pavinato L, Brusco A, Rosenfeld JA, Marom R, Wangler MF, Yamamoto S (2021) Drosophila functional screening of de novo variants in autism uncovers deleterious variants and facilitates discovery of rare neurodevelopmental diseases. bioRxiv 424813: *Contributed equally. Download PDF.   
Marcogliese PC*#, Dutta D*, Sinha-Ray S, Dang NDP, Zuo Z, Wang Y, Lu D, Fazal F, Ravenscroft TA, Chung HL, Kanca O, Wan J, Douine ED, Pena LDM, Yamamoto S, Nelson SF, Might M, Meyer KC, Yeo NC, Bellen HJ# (2021)  Loss of IRF2BPL impairs neuronal maintenance through excess Wnt signaling. Science Advances : in press (*co-first authors and #co-corresponding authors).   
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, MAE working group of EuroEPINOMICS RES Consortium, Mefford H, de Jonghe P, Yamamoto S, Weckhuysen S, Bellen HJ (2021) De novo FZR1 loss-of-function variants cause developmental and epileptic encephalopathy. Brain :doi: 10.1093/brain/awab409.  [Abstract]
Manor J, Chung HL, Bhagwat P, Wangle MF (2021) ABCD1 and X-linked adrenoleukodystrophy: A disease with a markedly variable phenotype showing conserved neurobiology in animal models.. Journal of Neuroscience Research 36:doi: 10.1002/jnr.24953.  [Abstract]
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)  Phosphatidylserine synthase plays an essential role in glia and affects development, as well as the maintenance of neuronal function. iScience :DOI: 10.1016/j.isci.2021.102899.  [Abstract]
Mok JW, Chung HL , Choi KW (2020) Calx, a sodium/calcium exchanger, may affect lifespan in Drosophila melanogastermicroPublication Biology 10:17912.  [Abstract]
Chung HL, Mao X, Wang H, Park YJ, Marcogliese PC, Rosenfels JA, Burrage LC, Liu P, Murdock DR, Yamamoto S, Wangler MF, Undiagnosed Diseases Network, Chao HT, Long H, Feng L, Bacino CA, Bellen HJ, Xiao B (2020) De novo variants in CDK19 are associated with a new syndrome with intellectual disability and epileptic encephalopathy. American Journal of Human Genetics 106:717-725.  [Abstract]
Chung HL, Wangler MF, Marcogliese PC, Jo J, Ravenscroft TA, Zuo Z, Duraine L, Sadeghzadeh S, Li-Kroeger D, Schmidt RE, Pestronk A, Rosenfeld JA, Burrage L, Herndon MJ, Chen S, Undiagnosed Diseases Network, Shillington A, Vawter-Lee M, Hopkin R, Rodriguez-Smith J, Henrickson M, Lee B, Moser AB, Jones RO, Watkins P, Yoo T, Mar S, Choi M, Bucelli RC, Yamamoto S, Lee HK, Prada CE, Chae JH, Vogel TP, Bellen HJ (2020) Loss or gain of function mutations in ACOX1 cause axonal loss via different mechanisms. Neuron 106:589-606.  [Abstract]
Link N, Chung HL, 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) Mutations in ANKLE2, a ZIKA virus target, disrupt an asymmetric cell division pathway in Drosophila neuroblasts to cause microcephaly. Developmental Cell 51:713-729.  [Abstract]
Kanca O, Zirin J, Garcia-Marques J, Knight SM, Yang-Zhou D, Amador G, Chung HL, 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) An efficient CRISPR-based strategy to insert small and large fragments of DNA using short homology arms. eLife 8:e51539.  [Abstract]
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) Bi-allelic variants in IQSEC1 cause intellectual disability, developmental delay and short stature. American Journal of Human Genetics 105:907-920. (*equal contribution) [Abstract]
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 GC, Bellen HJ, Antonarakis SE (2018) Bi-allelic loss-of-function variants in DNMBP cause infantile cataracts. American Journal of Human Genetics 103:568-578. (*equal contribution) [Abstract]
Marcogliese PC, Shashi V, Spillmann RC, Stong N, Rosenfeld JA, Koenig MK, Martínez-Agosto JA, Herzog M, Chen AH, Dickson PI, Lin HJ, Vera MU, Salamon N, Graham JM Jr, Ortiz D, Infante E, Steyaert W, Dermaut B, Poppe B, Chung HL, Zuo Z, Lee PT, Kanca O, Xia F, Yang Y, Smith EC, Jasien J, Kansagra S, Spiridigliozzi G, El-Dairi M, Lark R, Riley K, Koeberl DD, Golden-Grant K; Program for Undiagnosed Diseases (UD-PrOZA); Undiagnosed Diseases Network, Yamamoto S, Wangler MF, Mirzaa G, Hemelsoet D, Lee B, Nelson SF, Goldstein DB, Bellen HJ, Pena LDM (2018) IRF2BPL is associated with neurological phenotypes. American Journal of Human Genetics 103:245-260.  [Abstract]
Ansar M*, Chung HL*, 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) Visual impairment and progressive phthisis bulbi caused by recessive pathogenic variant in MARK3Human Molecular Genetics 27:2703-2711. (*equal contribution) [Abstract]
Chung HL, Choi KW (2016) Schip1, a new upstream regulator of Hippo signaling. Cell Cycle 15:2097-2098.  [Abstract]
Chung HL, Augustine GJ, Choi KW (2016) Drosophila Schip1 links Expanded and Tao-1 to regulate Hippo signaling. Developmental Cell 36:511-524.  [Abstract]

Last Modified 07-22-2022 by Zhongyuan Zuo

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