Publications
* Co-first authors
** Co-corresponding authors
As a corresponding author of Korea University College of Medicine
2024
65. Oh SJ, Kim YY, Ma R, Choi ST, Han K, Park H, Yun J**, Shin OS** (2024) in preparation.
64. Jang DC*, Kim SY*, Kim WS*, Jung H, Chung C, Bang S, Kim HN, Choi HW, Han K, Cho Y**, Kwon SK** (2024) submitted.
63. Ko TH*, Kim Y*, Jin C*, Yu B, Lee M, Luong PK, Trinh TN, Yang Y, Kang H, Zhang Y, Ma R, Yoo K, Choi J, Kim JY, Woo SH, Han K**, Choi JI** (2024) Shank3 overexpression leads to cardiac dysfunction in mice by disrupting calcium homeostasis in cardiomyocytes. Korean Circ J in revision.
62. Ma R, Han K (2024) Concerns regarding the interpretation of Shank3 protein isoforms expressed in Shank3B-/- mice: potential off-target effects by a neomycin resistance cassette. Mol Psychiatry under review.
61. Zhang Y*, Kang HR*, Jun Y*, Kang H*, Bang G, Ma R, Ju S, Yoon DE, Kim Y, Kim K, Kim JY**, Han K** (2024) Neurodevelopmental disorder-associated CYFIP2 regulates membraneless organelles and eIF2α phosphorylation via protein interactors and actin cytoskeleton. Hum Mol Genet http://10.1093/hmg/ddae107.
60. Okuzono S, Fujii F, Setoyama D, Taira R, Shinmyo Y, Kato H, Masuda K, Yonemoto K, Akamine S, Matsushita Y, Motomura Y, Sakurai T, Kawasaki H, Han K, Kato TA, Torisu H, Kang D, Nakabeppu Y, Ohga S, Sakai Y (2024) An N-terminal and ankyrin repeat domain interactome of Shank3 identifies the protein complex with the splicing regulator Nono in mice. Genes Cells http://doi.org/10.1111/gtc.13142.
59. Kim Y*, Ma R*, Zhang Y, Kang HR, Kim US, Han K (2024) Cell-autonomous reduction of CYFIP2 changes dendrite length, dendritic protrusion morphology, and inhibitory synapse density in the hippocampal CA1 pyramidal neurons of 17-month-old mice. Animal Cells Syst 28:294–302.
58. Cui M, Lee S, Ban SH, Ryu JR, Shen M, Yang SH, Kim JY, Choi SK, Han J, Kim Y, Han K, Lee D, Sun W, Kwon HB, Lee D (2024) A single-component, light-assisted uncaging switch for endoproteolytic release. Nat Chem Biol 20, 353-364.
2023
57. Yoon J, Moon JH, Chung J, Kim YJ, Kim K, Kang HS, Jeon YS, Oh E, Lee SH, Han K, Lee D, Lee CH, Kim YK, Lee D (2023) Exploring the Magnetic Properties of Individual Barcode Nanowires using Wide-Field Diamond Microscopy. Small 19:e2304129.
56. Okuzono S, Fujii F, Matsushita Y, Setoyama D, Shinmyo Y, Taira R, Yonemoto K, Akamine S, Motomura Y, Sanefuji M, Sakurai T, Kawasaki H, Han K, Kato TA, Torisu H, Kang D, Nakabeppu Y, Sakai Y, Ohga S (2023) Shank3a/b isoforms regulate the susceptibility to seizures and thalamocortical development in the early postnatal period of mice. Neurosci Res 193:13-19.
55. Kim Y*, Ko TH*, Jin C, Zhang Y, Kang HR, Ma R, Li H, Choi J-I**, Han K** (2023) The emerging roles of Shank3 in cardiac function and dysfunction. Front Cell Dev Biol 11:1191369.
54. Ma R, Zhang Y, Li H, Kang HR, Kim Y, Han K (2023) Cell-autonomous reduction of CYFIP2 is insufficient to induce Alzheimer’s disease-like pathologies in the hippocampal CA1 pyramidal neurons of aged mice. Animal Cells Syst 27:93–101.
53. Lee S, Cui M, Lee D, Han K, Sun W, Lee D (2023) A rationally designed optochemogenetic switch for activating canonical Wnt signaling. iScience 106233.
52. Kang M*, Zhang Y*, Kang HR*, Kim S, Ma R, Kim Y, Li H, Jin C, Lee D, Kim E**, Han K** (2023) CYFIP2 p.Arg87Cys causes neurological defects and degradation of CYFIP2. Ann Neurol 93:155–163.
2022
51. Kim SY, Strucinska K, Osei B, Han K, Kwon SK**, Lewis TL Jr** (2022) Neuronal mitochondrial morphology is significantly affected by both fixative and oxygen level during perfusion. Front Mol Neurosci 15:1042616.
50. Cui J, Ju X, Lee Y, Hong B, Kang H, Han K, Shin WH, Park J, Lee MJ, Kim YH, Ko Y, Heo JY**, Chung W** (2022) Repeated ketamine anesthesia during neurodevelopment upregulates hippocampal activity and enhances drug reward in male mice. Commun Biol 5:709.
49. Ma R*, Pang K*, Kang H*, Zhang Y*, Bang G, Park S, Hwang E, Ryu JR, Kwon Y, Kang HR, Jin C, Kim Y, Kim SY, Kwon SK, Kim D, Sun W, Kim JY**, Han K** (2022) Protein interactome and cell-type expression analyses reveal that cytoplasmic FMR1-interacting protein 1 (CYFIP1), but not CYFIP2, associates with astrocytic focal adhesion. J Neurochem 162:190–206.
(Issue cover)
The two members of the cytoplasmic FMR1-interacting protein family, CYFIP1 and CYFIP2, are evolutionarily conserved multifunctional proteins whose defects are associated with numerous brain disorders including schizophrenia, intellectual disability, and epilepsy. Although several lines of evidence indicate different roles of CYFIP1 and CYFIP2 in vivo, cell type-specific expression and function of CYFIP1 and CYFIP2 in the brain remain largely unknown. In this study, we combined protein interactome, cell-type expression, and gene coexpression analyses to reveal the predominant expression of CYFIP1, but not CYFIP2, in astrocytes where it associates with focal adhesion proteins. These results provide further insights into the mechanisms of different brain functions and dysfunctions of CYFIP1 and CYFIP2.
2021
48. Holder JL, Pang K, Weiwer M, Han K, Wang W, Estiphan T, Vuocolo B, Jaunarajs K, Holson E, Lewis M, Xu Q, Gale J, Pedersen S, Pautler R, Standaert D, Wagner F, Liu Z, Zoghbi HY (2021) Dysfunction of D2 dopamine receptor expressing neurons underlies manic-like behaviors in mice modeling SHANK3 duplication disorder. Research Square (preprint) DOI: https://doi.org/10.21203/rs.3.rs-646721/v1.
47. Jin C*, Lee Y*, Kang H*, Jeong K, Park J, Zhang Y, Kang HR, Ma R, Seong H, Kim Y, Jung H, Kim JY, Kim YK, Han K (2021) Increased ribosomal protein levels and protein synthesis in the striatal synaptosome of Shank3-overexpressing transgenic mice. Mol Brain 14:39.
46. Jin C*, Kang H*, Yoo T*, Ryu JR, Yoo YE, Ma R, Zhang Y, Kang HR, Kim Y, Seong H, Bang G, Park S, Kwon SK, Sun W, Kim H, Kim JY, Kim E, Han K (2021) The neomycin resistance cassette in the targeted allele of Shank3B knock-out mice has potential off-target effects to produce an unusual Shank3 isoform. Front Mol Neurosci 13:614435.
2020
45. Zhang Y*, Kang HR*, Lee SH*, Kim Y, Ma R, Jin C, Lim JE, Kim S, Kang Y, Kang H, Kim SY, Kwon SK, Choi SY**, Han K** (2020) Enhanced prefrontal neuronal activity and social dominance behavior in postnatal forebrain excitatory neuron-specific Cyfip2 knock-out mice. Front Mol Neurosci 13:574947.
44. Kim GH*, Zhang Y*, Kang HR*, Lee SH*, Shin J, Lee CH, Kang H, Ma R, Jin C, Kim Y, Kim SY, Kwon SK, Choi SY**, Lee KJ**, Han K** (2020) Altered presynaptic function and number of mitochondria in the medial prefrontal cortex of adult Cyfip2 heterozygous mice. Mol Brain 13:123.
43. Lee SH*, Zhang Y*, Park J, Kim B, Kim Y, Lee SH, Kim GH, Huh YH, Lee B, Kim Y, Lee Y, Kim JY, Kang H, Choi SY, Jang S, Li Y, Kim S, Jin C, Pang K, Kim E, Lee Y, Kim H, Kim E, Choi JH, Kim J, Lee KJ**, Choi SY**, Han K** (2020) Haploinsufficiency of Cyfip2 Causes Lithium-Responsive Prefrontal Dysfunction. Ann Neurol 88:526-543.
(Issue cover)
A pair of reconstructions of serial blockface scanning electron microscopic images showing dendritic spines (blue) on dendrites (gray) of pyramidal cells in the prefrontal cortex, in a wildtype mouse (left) and in a mouse that is heterozygous for a null mutation in the Cyfip2 gene (right). Null mutations of this gene on one copy of chromosome 5 in humans are associated with intellectual disability and seizures. Mice with deletion of one copy of the gene have similar problems and their cortical neurons show enlarged dendritic spines (shown here) with reduced expression of potassium channels, thus predisposing to hyperexcitability which can be normalized with lithium treatment.
42. Pang K*, Wang L*, Wang W, Zhou J, Cheng C, Han K, Zoghbi HY, Liu Z (2020) Coexpression enrichment analysis at the single-cell level reveals convergent defects in neural progenitor cells and their cell-type transitions in neurodevelopmental disorders. Genome Res 30:835-848.
41. Lee Y*, Zhang Y*, Kang H*, Bang G, Kim Y, Kang HR, Ma R, Jin C, Kim JY**, Han K** (2020) Epilepsy- and intellectual disability-associated CYFIP2 interacts with both actin regulators and RNA-binding proteins in the mouse neonatal forebrain. Biochem Biophys Res Commun 529:1-6.
40. Ey E**, Bourgeron T**, Boeckers TM**, Kim E**, Han K** (2020) Editorial: Shankopathies: Shank Protein Deficiency-Induced Synaptic Diseases. Front Mol Neurosci 13:11.
39. Wang L, Adamski C, Bondar V, Craigen E, Collette J, Pang K, Han K, Jain A, Jung SY, Liu Z, Sifers R, Holder JL**, Zoghbi HY** (2020) A kinome-wide RNAi screen identifies ERK2 as a druggable regulator of Shank3 stability. Mol Psychiatry 25:2504-2516.
38. Wang L, Pang K, Han K, Adamski C, Wang W, He L, Lai J, Bondar V, Duman J, Richman R, Tolias K, Barth P, Palzkill T, Liu Z, Holder JL**, Zoghbi HY** (2020) An autism-linked missense mutation in SHANK3 reveals modularity of Shank3 function. Mol Psychiatry 25:2534-2555.
2019
37. Zhang Y*, Kang HR*, Han K (2019) Differential cell-type-expression of CYFIP1 and CYFIP2 in the adult mouse hippocampus. Animal Cells Syst 23:380-383.
36. Lee Y, Zhang Y, Ryu JR, Kang HR, Kim D, Jin C, Kim Y, Sun W, Han K (2019) Reduced CYFIP2 stability by Arg87 variants causing human neurological disorders. Ann Neurol 86:803-805.
35. Jin C*, Kim S*, Kang H*, Yun KN, Lee Y, Zhang Y, Kim Y, Kim JY**, Han K** (2019) Shank3 regulates striatal synaptic abundance of Cyld, a deubiquitinase specific for Lys63-linked polyubiquitin chains. J Neurochem 150:776-786.
34. Jin C*, Kang HR*, Kang H*, Zhang Y, Lee Y, Kim Y, Han K (2019) Unexpected compensatory increase in Shank3 transcripts in Shank3 knock-out mice having partial deletions of exons. Front Mol Neurosci 12:228.
33. Pahk K, Noh H, Joung C, Jang M, Song HY, Kim KW, Han K, Hwang JI, Kim S, Kim W (2019) A novel CD147 inhibitor, SP-8356, reduces neointimal hyperplasia and arterial stiffness in a rat model of partial carotid artery ligation. J Transl Med 17:274.
32. Lee Y*, Kang H*, Jin C*, Zhang Y, Kim Y, Han K (2019) Transcriptome analyses suggest minimal effects of Shank3 dosage on directional gene expression changes in the mouse striatum. Animal Cells Syst 23:270-274.
31. Zhang Y, Lee Y, Han K (2019) Neuronal function and dysfunction of CYFIP2: from actin dynamics to early infantile epileptic encephalopathy. BMB Rep 52:304-311.
30. Kim S*, Zhang Y*, Jin C*, Lee Y, Kim Y, Han K (2019) Emerging roles of Lys63-linked polyubiquitination in neuronal excitatory postsynapses. Arch Pharm Res 42:285-292.
(Issue cover)
In the mammalian brain, neuronal excitatory synaptic development, function, and plasticity largely rely on dynamic, activity-dependent changes in the macromolecular protein complex called the postsynaptic density (PSD). Activity-dependent Lys48-linked polyubiquitination and subsequent proteasomal degradation of key proteins in the PSD have been reported. However, investigations into the functions and regulatory mechanisms of Lys63-linked polyubiquitination, the second most abundant polyubiquitin form in synapses, have recently begun. Recent studies showed that a Lys63 linkage-specific deubiquitinase (DUB), cylindromatosis-associated DUB (CYLD) localizes to the PSD where its DUB activity is regulated by different kinases. In addition, Lys63-linked polyubiquitination of postsynaptic density 95 (PSD-95), a core scaffolding protein of the PSD, was identified and its functional significance in synaptic plasticity was characterized. In this review, we summarize these recent findings on Lys63-linked polyubiquitination in excitatory postsynapses, and also propose key questions and prospects about this emerging type of posttranslational modification of the PSD proteome.
29. Zhang Y*, Kang H*, Lee Y, Kim Y, Lee B, Kim JY, Jin C, Kim S, Kim H, Han K (2019) Smaller body size, early postnatal lethality, and cortical extracellular matrix-related gene expression changes of Cyfip2-null embryonic mice. Front Mol Neurosci 11:482.
2018
28. Jin C*, Kang H*, Kim S, Zhang Y, Lee Y, Kim Y, Han K (2018) Transcriptome analysis of Shank3-overexpressing mice reveals unique molecular changes in the hypothalamus. Mol Brain 11:71.
27. Jin C*, Zhang Y*, Kim S, Kim Y, Lee Y, Han K (2018) Spontaneous seizure and partial lethality of juvenile Shank3-overexpressing mice in C57BL/6J background. Mol Brain 11:57.
26. Jin C*, Kang H*, Ryu JR, Kim S, Zhang Y, Lee Y, Kim Y, Han K (2018) Integrative brain transcriptome analysis reveals region-specific and broad molecular changes in Shank3-overexpressing mice. Front Mol Neurosci 11:250.
25. Lee Y, Zhang Y, Kim S, Han K (2018) Excitatory and inhibitory synaptic dysfunction in mania: an emerging hypothesis from animal model studies. Exp Mol Med 50:12.
2017
24. Lee Y, Ryu JR, Kang H, Kim Y, Kim S, Zhang Y, Jin C, Cho HM, Kim WK, Sun W, Han K (2017) Characterization of the zinc-induced Shank3 interactome of mouse synaptosome. Biochem Biophys Res Commun 494:581-586.
23. Lee Y*, Kim D*, Ryu JR, Zhang Y, Kim S, Kim Y, Lee B, Sun W, Han K (2017) Phosphorylation of CYFIP2, a component of WAVE regulatory complex, regulates dendritic spine density and neurite outgrowth in cultured hippocampal neurons potentially by affecting the complex assembly. NeuroReport 28:749-754.
22. Lee Y, Kim SG, Lee B, Zhang Y, Kim Y, Kim S, Kim E, Kang H**, Han K** (2017) Striatal transcriptome and interactome analysis of Shank3-overexpressing mice reveals the connectivity between Shank3 and mTORC1 signaling. Front Mol Neurosci 10:201.
21. Lee B*, Zhang Y*, Kim Y*, Kim S, Lee Y, Han K (2017) Age-dependent decrease of GAD65/67 mRNAs but normal densities of GABAergic interneurons in the brain regions of Shank3-overexpressing manic mouse model. Neurosci Lett 649:48-54.
20. Lee Y*, Kang H*, Lee B, Zhang Y, Kim Y, Kim S, Kim WK, Han K (2017) Integrative analysis of brain region-specific Shank3 interactomes for understanding the heterogeneity of neuronal pathophysiology related to SHANK3 mutations. Front Mol Neurosci 10:110.
19. Roh JD*, Choi SY*, Cho YS, Choi TY, Park JS, Cutforth T, Chung W, Park H, Lee D, Kim MH, Lee Y, Mo S, Rhee JS, Kim H, Ko J, Choi SY, Bae YC, Shen K**, Kim E**, Han K** (2017) Increased excitatory synaptic transmission of dentate granule neurons in mice lacking PSD-95-interacting adhesion molecule Neph2/Kirrel3 during the early postnatal period. Front Mol Neurosci 10:81.
2016
18. Kim Y*, Zhang Y*, Pang K*, Kang H, Park H, Lee Y, Lee B, Lee HJ, Kim WK, Geum D, Han K (2016) Bipolar disorder associated microRNA, miR-1908-5p, regulates the expression of genes functioning in neuronal glutamatergic synapses. Exp Neurobiol 25:296-306.
2015
17. Choi SY, Pang K, Kim JY, Ryu JR, Kang H, Liu Z, Kim WK, Sun W, Kim H, Han K (2015) Post-transcriptional regulation of SHANK3 expression by microRNAs related to multiple neuropsychiatric disorders. Mol Brain 8:74.
16. Choi SY, Han K (2015) Emerging role of synaptic actin-regulatory pathway in the pathophysiology of mood disorders. Animal Cells Syst 19:283-288.
15. Choi SY, Han K, Cutforth T, Chung W, Park H, Lee D, Kim R, Kim MH, Choi Y, Shen K**, Kim E** (2015) Mice lacking the synaptic adhesion molecule Neph2/Kirrel3 display moderate hyperactivity and defective novel object preference. Front Cell Neurosci 9:283.
Publications prior to joining Korea University
First author papers
14. Han K**, Chen H, Gennarino VA, Richman R, Lu HC, Zoghbi HY** (2015) Fragile X-like behaviors and abnormal cortical dendritic spines in Cytoplasmic FMR1-interacting protein 2-mutant mice. Hum Mol Genet 24:1813-1823.
13. Gennarino VA, Singh RK, White JJ, De Maio A, Han K, Kim JY, Jafar-Nejad P, di Ronza A, Kang H, Sayegh LS, Cooper TA, Orr HT, Sillitoe RV, Zoghbi HY (2015) Pumilio1 Haploinsufficiency Leads to SCA1-like Neurodegeneration by Increasing Wild-Type Ataxin1 Levels. Cell 160:1087-1098.
12. Han K, Holder JL, Jr., Schaaf CP, Lu H, Chen H, Kang H, Tang J, Wu Z, Hao S, Cheung SW, Yu P, Sun H, Breman AM, Patel A, Lu HC, Zoghbi HY (2013) SHANK3 overexpression causes manic-like behaviour with unique pharmacogenetic properties. Nature 503:72-77.
(Issue cover, Journal Article, Highlighted in Nature News, Cell Select, Science Translational Medicine Editor’s choice, F1000Prime, SFARI and NIH director’s blog)
Mutations in SHANK3, the gene encoding the SHANK3 synaptic scaffolding protein, are associated with autism, intellectual disability and schizophrenia, but the effect of SHANK3 overexpression is much less clear. Huda Zoghbi and colleagues now show that mice overexpressing Shank3 exhibit mania-like behaviour, seizures and alterations in excitatory/inhibitory balance of neuronal activity. Consistent with the findings in mouse, they identify two patients with hyperkinetic disorders carrying a genetic duplication of the SHANK3-containing region on chromosome 22. These findings support the hypothesis that incorrect gene dosage in either direction (both over- and under-expression) may be detrimental. The authors suggest that the mice used in this work provide a model for the pharmacogenetic underpinnings of some forms of bipolar disorder.
11. Bae YS, Chung W, Han K, Park KY, Kim H, Kim E, Kim MH (2013) Down-regulation of RalBP1 expression reduces seizure threshold and synaptic inhibition in mice. Biochem Biophys Res Commun 433:175-180.
10. Han K*, Gennarino VA*, Lee Y, Pang K, Hashimoto-Torii K, Choufani S, Raju CS, Oldham MC, Weksberg R, Rakic P, Liu Z, Zoghbi HY (2013) Human-specific regulation of MeCP2 levels in fetal brains by microRNA miR-483-5p. Genes Dev 27:485-490.
(Issue cover)
Regulation of the methyl CpG-binding protein 2 (MeCP2) by miR-483-5p in human fetal brains is required for normal neurological function. Shown here is a confocal image of a cultured hippocampal neuron overexpressing human MECP2, with a microRNA structure presented in the middle. miR-483-5p is a fetal-enriched intragenic microRNA of the imprinted gene IGF2, which regulates MeCP2 levels through a human-specific binding site in the MECP2 long 3′ UTR.
9. Sim SE, Lee HR, Kim JI, Choi SL, Bakes J, Jang DJ, Lee K, Han K, Kim E, Kaang BK (2013) Elevated RalA activity in the hippocampus of PI3Kgamma knock-out mice lacking NMDAR-dependent long-term depression. BMB Rep 46:103-106.
8. Yang J*, Seo J*, Nair R, Han S, Jang S, Kim K, Han K, Paik SK, Choi J, Lee S, Bae YC, Topham MK, Prescott SM, Rhee JS, Choi SY, Kim E (2011) DGKiota regulates presynaptic release during mGluR-dependent LTD. Embo J 30:165-180.
7. Han S*, Nam J*, Li Y*, Kim S, Cho SH, Cho YS, Choi SY, Choi J, Han K, Kim Y, Na M, Kim H, Bae YC, Kim E (2010) Regulation of dendritic spines, spatial memory, and embryonic development by the TANC family of PSD-95-interacting proteins. J Neurosci 30:15102-15112.
6. Mah W*, Ko J*, Nam J*, Han K, Chung WS, Kim E (2010) Selected SALM (synaptic adhesion-like molecule) family proteins regulate synapse formation. J Neurosci 30:5559-5568.
5. Lee HW, Kim Y, Han K, Kim H, Kim E (2010) The phosphoinositide 3-phosphatase MTMR2 interacts with PSD-95 and maintains excitatory synapses by modulating endosomal traffic. J Neurosci 30:5508-5518.
4. Han K*, Kim MH*, Seeburg D, Seo J, Verpelli C, Han S, Chung HS, Ko J, Lee HW, Kim K, Heo WD, Meyer T, Kim H, Sala C, Choi SY, Sheng M, Kim E (2009) Regulated RalBP1 binding to RalA and PSD-95 controls AMPA receptor endocytosis and LTD. PLoS Biol 7:e1000187.
(Highlighted in Faculty of 1000 Biology)
3. Kim K, Yang J, Zhong XP, Kim MH, Kim YS, Lee HW, Han S, Choi J, Han K, Seo J, Prescott SM, Topham MK, Bae YC, Koretzky G, Choi SY, Kim E (2009) Synaptic removal of diacylglycerol by DGKzeta and PSD-95 regulates dendritic spine maintenance. Embo J 28:1170-1179.
2. Han K, Kim E (2008) Synaptic adhesion molecules and PSD-95. Prog Neurobiol 84:263-283.
1. Ko J, Kim S, Chung HS, Kim K, Han K, Kim H, Jun H, Kaang BK, Kim E (2006) SALM synaptic cell adhesion-like molecules regulate the differentiation of excitatory synapses. Neuron 50:233-245.