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Ki Taek Nam
Severance Biomedical Science Institute, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea

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Stomach
Published: 13 August 2021 in Gut
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Objective Gastric cancer (GC) is a leading cause of cancer-related mortality. Although microbes besides Helicobacter pylori may also contribute to gastric carcinogenesis, wild-type germ-free (GF) mouse models investigating the role of human gastric microbiota in the process are not yet available. We aimed to evaluate the histopathological features of GF mouse stomachs transplanted with gastric microbiota from patients with different gastric disease states and their relationships with the microbiota. Design Microbiota profiles in corpus and antrum tissues and gastric fluid from 12 patients with gastric dysplasia or GC were analysed. Thereafter, biopsied corpus and antrum tissues and gastric fluid from patients (n=15 and n=12, respectively) with chronic superficial gastritis, intestinal metaplasia or GC were inoculated into 42 GF C57BL/6 mice. The gastric microbiota was analysed by amplicon sequencing. Histopathological features of mouse stomachs were analysed immunohistochemically at 1 month after inoculation. An independent set of an additional 15 GF mice was also analysed at 1 year. Results The microbial community structures of patients with dysplasia or GC in the corpus and antrum were similar. The gastric microbiota from patients with intestinal metaplasia or GC selectively colonised the mouse stomachs and induced premalignant lesions: loss of parietal cells and increases in inflammation foci, in F4/80 and Ki-67 expression, and in CD44v9/GSII lectin expression. Marked dysplastic changes were noted at 1 year post inoculation. Conclusion Major histopathological features of premalignant changes are reproducible in GF mice transplanted with gastric microbiota from patients with intestinal metaplasia or GC. Our results suggest that GF mice are useful for analysing the causality of associations reported in human gastric microbiome studies.

ACS Style

Soon-Kyeong Kwon; Jun Chul Park; Kwang H Kim; Jaekyung Yoon; Yejin Cho; Buhyun Lee; Jin-Jae Lee; Haengdueng Jeong; Yeseul Oh; Sung-Hee Kim; So Dam Lee; Bo Ram Hwang; Yusook Chung; Jihyun F Kim; Ki Taek Nam; Yong Chan Lee. Human gastric microbiota transplantation recapitulates premalignant lesions in germ-free mice. Gut 2021, 1 .

AMA Style

Soon-Kyeong Kwon, Jun Chul Park, Kwang H Kim, Jaekyung Yoon, Yejin Cho, Buhyun Lee, Jin-Jae Lee, Haengdueng Jeong, Yeseul Oh, Sung-Hee Kim, So Dam Lee, Bo Ram Hwang, Yusook Chung, Jihyun F Kim, Ki Taek Nam, Yong Chan Lee. Human gastric microbiota transplantation recapitulates premalignant lesions in germ-free mice. Gut. 2021; ():1.

Chicago/Turabian Style

Soon-Kyeong Kwon; Jun Chul Park; Kwang H Kim; Jaekyung Yoon; Yejin Cho; Buhyun Lee; Jin-Jae Lee; Haengdueng Jeong; Yeseul Oh; Sung-Hee Kim; So Dam Lee; Bo Ram Hwang; Yusook Chung; Jihyun F Kim; Ki Taek Nam; Yong Chan Lee. 2021. "Human gastric microbiota transplantation recapitulates premalignant lesions in germ-free mice." Gut , no. : 1.

Research article
Published: 28 May 2021 in Science Advances
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Since the emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), various vaccines are being developed, with most vaccine candidates focusing on the viral spike protein. Here, we developed a previously unknown subunit vaccine comprising the receptor binding domain (RBD) of the spike protein fused with the tetanus toxoid epitope P2 (RBD-P2) and tested its efficacy in rodents and nonhuman primates (NHPs). We also investigated whether the SARS-CoV-2 nucleocapsid protein (N) could increase vaccine efficacy. Immunization with N and RBD-P2 (RBDP2/N) + alum increased T cell responses in mice and neutralizing antibody levels in rats compared with those obtained using RBD-P2 + alum. Furthermore, in NHPs, RBD-P2/N + alum induced slightly faster SARS-CoV-2 clearance than that induced by RBD-P2 + alum, albeit without statistical significance. Our study supports further development of RBD-P2 as a vaccine candidate against SARS-CoV-2. Also, it provides insights regarding the use of N in protein-based vaccines against SARS-CoV-2.

ACS Style

So-Hee Hong; Hanseul Oh; Yong Wook Park; Hye Won Kwak; Eun Young Oh; Hyo-Jung Park; Kyung Won Kang; Green Kim; Bon-Sang Koo; Eun-Ha Hwang; Seung Ho Baek; Hyeong-Jun Park; Yu-Sun Lee; Yoo-Jin Bang; Jae-Yong Kim; Seo-Hyeon Bae; Su Jeen Lee; Ki-Weon Seo; Hak Kim; Taewoo Kwon; Ji-Hwan Kim; SeongHwan Lee; Eunsom Kim; Yeonhwa Kim; Jae-Hak Park; Sang-In Park; Marta Gonçalves; Byung Mook Weon; Haengdueng Jeong; Ki Taek Nam; Kyung-Ah Hwang; Jihye Kim; Hun Kim; Sang-Myeong Lee; Jung Joo Hong; Jae-Hwan Nam. Immunization with RBD-P2 and N protects against SARS-CoV-2 in nonhuman primates. Science Advances 2021, 7, eabg7156 .

AMA Style

So-Hee Hong, Hanseul Oh, Yong Wook Park, Hye Won Kwak, Eun Young Oh, Hyo-Jung Park, Kyung Won Kang, Green Kim, Bon-Sang Koo, Eun-Ha Hwang, Seung Ho Baek, Hyeong-Jun Park, Yu-Sun Lee, Yoo-Jin Bang, Jae-Yong Kim, Seo-Hyeon Bae, Su Jeen Lee, Ki-Weon Seo, Hak Kim, Taewoo Kwon, Ji-Hwan Kim, SeongHwan Lee, Eunsom Kim, Yeonhwa Kim, Jae-Hak Park, Sang-In Park, Marta Gonçalves, Byung Mook Weon, Haengdueng Jeong, Ki Taek Nam, Kyung-Ah Hwang, Jihye Kim, Hun Kim, Sang-Myeong Lee, Jung Joo Hong, Jae-Hwan Nam. Immunization with RBD-P2 and N protects against SARS-CoV-2 in nonhuman primates. Science Advances. 2021; 7 (22):eabg7156.

Chicago/Turabian Style

So-Hee Hong; Hanseul Oh; Yong Wook Park; Hye Won Kwak; Eun Young Oh; Hyo-Jung Park; Kyung Won Kang; Green Kim; Bon-Sang Koo; Eun-Ha Hwang; Seung Ho Baek; Hyeong-Jun Park; Yu-Sun Lee; Yoo-Jin Bang; Jae-Yong Kim; Seo-Hyeon Bae; Su Jeen Lee; Ki-Weon Seo; Hak Kim; Taewoo Kwon; Ji-Hwan Kim; SeongHwan Lee; Eunsom Kim; Yeonhwa Kim; Jae-Hak Park; Sang-In Park; Marta Gonçalves; Byung Mook Weon; Haengdueng Jeong; Ki Taek Nam; Kyung-Ah Hwang; Jihye Kim; Hun Kim; Sang-Myeong Lee; Jung Joo Hong; Jae-Hwan Nam. 2021. "Immunization with RBD-P2 and N protects against SARS-CoV-2 in nonhuman primates." Science Advances 7, no. 22: eabg7156.

Research article
Published: 26 February 2021 in Science Advances
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Ionizable lipid nanoparticles (LNPs) have been widely used for in vivo delivery of RNA therapeutics into the liver. However, a main challenge remains to develop LNP formulations for selective delivery of RNA into certain types of liver cells, such as hepatocytes and liver sinusoidal endothelial cells (LSECs). Here, we report the engineered LNPs for the targeted delivery of RNA into hepatocytes and LSECs. The effects of particle size and polyethylene glycol–lipid content in the LNPs were evaluated for the hepatocyte-specific delivery of mRNA by ApoE-mediated cellular uptake through low-density lipoprotein receptors. Targeted delivery of RNA to LSECs was further investigated using active ligands. Incorporation of mannose allowed the selective delivery of RNA to LSECs, while minimizing the unwanted cellular uptake by hepatocytes. These results demonstrate that engineered LNPs have great potential for the cell type–specific delivery of RNA into the liver and other tissues.

ACS Style

M. Kim; M. Jeong; S. Hur; Y. Cho; J. Park; H. Jung; Y. Seo; H. A. Woo; K. T. Nam; K. Lee; H. Lee. Engineered ionizable lipid nanoparticles for targeted delivery of RNA therapeutics into different types of cells in the liver. Science Advances 2021, 7, eabf4398 .

AMA Style

M. Kim, M. Jeong, S. Hur, Y. Cho, J. Park, H. Jung, Y. Seo, H. A. Woo, K. T. Nam, K. Lee, H. Lee. Engineered ionizable lipid nanoparticles for targeted delivery of RNA therapeutics into different types of cells in the liver. Science Advances. 2021; 7 (9):eabf4398.

Chicago/Turabian Style

M. Kim; M. Jeong; S. Hur; Y. Cho; J. Park; H. Jung; Y. Seo; H. A. Woo; K. T. Nam; K. Lee; H. Lee. 2021. "Engineered ionizable lipid nanoparticles for targeted delivery of RNA therapeutics into different types of cells in the liver." Science Advances 7, no. 9: eabf4398.

Journal article
Published: 15 February 2021 in Food and Chemical Toxicology
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Biocides are widely used in household products. Humans are exposed to biocides through dermal, inhalational, and oral routes. However, information on the dermal and inhalational toxicity of biocides is limited. We evaluated the effects of biocides on the skin and airways using the reconstructed human epidermis model KeraSkin™ and the airway model SoluAirway™. We determined the irritancy of 11 commonly used biocides (1,2-benzisothiazol-3(2H)-one [BIT], 2-phenoxyethanol [PE], zinc pyrithione, 2-bromo-2-nitropropane-1,3-diol, 3-iodoprop-2-ynyl N-butylcarbamate [IPBC], 2-octyl-1,2-thiazol-3-one, 2,2-dibromo-2-cyanoacetamide, 4-chloro-3-methylphenol [CC], 2-phenylphenol, deltamethrin, and 4,5-dichloro-2-octyl-1,2-thiazol-3-one) in the KeraSkin™ and SoluAirway™ by viability and histological examinations. BIT and CC were found to cause skin irritation at the approved concentrations or at the concentration close to approved limit while the others were non-irritants within the approved concentration. These results were confirmed via histology, wherein skin irritants induced erosion, vacuolation, and necrosis of the tissue. In the SoluAirway™, most of the biocides decreased cell viability even within the approved limits, except for PE, IPBC, and deltamethrin, suggesting that the airway may be more vulnerable to biocides than the skin. Taken together, our result indicates that some biocides can induce toxicity in skin and airway. Further studies on the dermal and inhalational toxicity of biocides are warranted.

ACS Style

Jee-Hyun Hwang; Haengdueng Jeong; Ye-On Jung; Ki Taek Nam; Kyung-Min Lim. Skin irritation and inhalation toxicity of biocides evaluated with reconstructed human epidermis and airway models. Food and Chemical Toxicology 2021, 150, 112064 .

AMA Style

Jee-Hyun Hwang, Haengdueng Jeong, Ye-On Jung, Ki Taek Nam, Kyung-Min Lim. Skin irritation and inhalation toxicity of biocides evaluated with reconstructed human epidermis and airway models. Food and Chemical Toxicology. 2021; 150 ():112064.

Chicago/Turabian Style

Jee-Hyun Hwang; Haengdueng Jeong; Ye-On Jung; Ki Taek Nam; Kyung-Min Lim. 2021. "Skin irritation and inhalation toxicity of biocides evaluated with reconstructed human epidermis and airway models." Food and Chemical Toxicology 150, no. : 112064.

Journal article
Published: 03 February 2021 in Toxics
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Biocides are commonly used as spray- or trigger-type formulations, thus dermal and respiratory exposure to biocide aerosol is unavoidable. However, little is known about the impact of aerosolization on the local toxicity of biocides on the skin or the airway. We compared the local toxicity of biocides after direct or aerosol exposure on reconstructed human skin epidermis and upper airway models. Three biocides, 1,2-benzisothiazol-3(2H)-one (BIT), 2-phenoxyethanol (PE), and 2-phenylphenol (OPP), most widely used in the market were selected. When the biocide was treated in aerosols, toxicity to the skin epidermis and upper airway tissue became significantly attenuated compared with the direct application as determined by the higher tissue viabilities. This was further confirmed in histological examination, wherein the tissue damages were less pronounced. LC-MS/MS and GC/MS analysis revealed that concentrations of biocides decreased during aerosolization. Importantly, the toxicity of biocides treated in 3 μm (median mass aerodynamic diameter (MMAD)) aerosols was stronger than that of 5 μm aerosol, suggesting that the aerosol particle size may affect biocide toxicity. Collectively, we demonstrated that aerosolization could affect the local toxicity of biocides on the skin epidermis and the upper airway.

ACS Style

Nahyun Lee; Dae Jang; Do Lee; Haengdueng Jeong; Ki Nam; Dal-Woong Choi; Kyung-Min Lim. Local Toxicity of Biocides after Direct and Aerosol Exposure on the Human Skin Epidermis and Airway Tissue Models. Toxics 2021, 9, 29 .

AMA Style

Nahyun Lee, Dae Jang, Do Lee, Haengdueng Jeong, Ki Nam, Dal-Woong Choi, Kyung-Min Lim. Local Toxicity of Biocides after Direct and Aerosol Exposure on the Human Skin Epidermis and Airway Tissue Models. Toxics. 2021; 9 (2):29.

Chicago/Turabian Style

Nahyun Lee; Dae Jang; Do Lee; Haengdueng Jeong; Ki Nam; Dal-Woong Choi; Kyung-Min Lim. 2021. "Local Toxicity of Biocides after Direct and Aerosol Exposure on the Human Skin Epidermis and Airway Tissue Models." Toxics 9, no. 2: 29.

Journal article
Published: 11 January 2021 in International Journal of Molecular Sciences
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Since the European Union (EU) announced their animal testing ban in 2013, all animal experiments related to cosmetics have been prohibited, creating a demand for alternatives to animal experiments for skin studies. Here, we investigated whether an ex vivo live porcine skin model can be employed to study the safety and skin barrier-improving effects of hydroxyacids widely used in cosmetics for keratolytic peels. Glycolic acid (1–10%), salicylic acid (0.2–2%), and lactobionic acid (1.2–12%) were used as representative substances for α-hydroxyacid (AHA), β-hydroxyacid (BHA), and polyhydroxyacid (PHA), respectively. When hydroxyacids were applied at high concentrations on the porcine skin every other day for 6 days, tissue viability was reduced to 50–80%, suggesting that the toxicity of cosmetic ingredients can be evaluated with this model. Based on tissue viability, the treatment scheme was changed to a single exposure for 20 min. The protective effects of a single exposure of hydroxyacids on skin barrier function were evaluated by examining rhodamine permeability and epidermal structural components of barrier function using immunohistochemistry (IHC) and immunofluorescence (IF) staining. Lactobionic acid (PHAs) improved skin barrier function most compared to other AHAs and BHAs. Most importantly, trans-epidermal water loss (TEWL), an important functional marker of skin barrier function, could be measured with this model, which confirmed the significant skin barrier-protective effects of PHAs. Collectively, we demonstrated that the ex vivo live full-thickness porcine skin model can be an excellent alternative to animal experiments for skin studies on the safety and efficacy of cosmetic ingredients.

ACS Style

Jee-Hyun Hwang; Haengdueng Jeong; Nahyun Lee; Sumin Hur; Nakyum Lee; Jeong Jun Han; Hye Won Jang; Wang Keun Choi; Ki Taek Nam; Kyung-Min Lim. Ex Vivo Live Full-Thickness Porcine Skin Model as a Versatile In Vitro Testing Method for Skin Barrier Research. International Journal of Molecular Sciences 2021, 22, 657 .

AMA Style

Jee-Hyun Hwang, Haengdueng Jeong, Nahyun Lee, Sumin Hur, Nakyum Lee, Jeong Jun Han, Hye Won Jang, Wang Keun Choi, Ki Taek Nam, Kyung-Min Lim. Ex Vivo Live Full-Thickness Porcine Skin Model as a Versatile In Vitro Testing Method for Skin Barrier Research. International Journal of Molecular Sciences. 2021; 22 (2):657.

Chicago/Turabian Style

Jee-Hyun Hwang; Haengdueng Jeong; Nahyun Lee; Sumin Hur; Nakyum Lee; Jeong Jun Han; Hye Won Jang; Wang Keun Choi; Ki Taek Nam; Kyung-Min Lim. 2021. "Ex Vivo Live Full-Thickness Porcine Skin Model as a Versatile In Vitro Testing Method for Skin Barrier Research." International Journal of Molecular Sciences 22, no. 2: 657.

Journal article
Published: 25 September 2020 in Cancer Letters
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Approximately 70% of breast cancers are estrogen receptor (ER)-positive and treated with endocrine therapy. A commonly used treatment agent, tamoxifen, shows high efficacy for improving prognosis. However, approximately one-third of patients treated with tamoxifen develop resistance to this drug. Here, we investigated the function of general control non-derepressible 5 (GCN5) and its downstream effectors in tamoxifen-resistant (TamR) breast cancer. TamR-MCF7 breast cancer cells maintained high GCN5 levels due to its attenuated proteasomal degradation. GCN5 overexpression upregulated amplified in breast cancer 1 (AIB1) expression, resulting in decreased p53 stability and tamoxifen resistance. Conversely, the sensitivity of GCN5-AIB1-overexpressing MCF7 cells to tamoxifen was restored by forced p53 expression. An in vivo study demonstrated a positive correlation between GCN5 and AIB1 and their contribution to tamoxifen resistance. We concluded that GCN5 promotes AIB1 expression and tamoxifen resistance in breast cancer by reducing p53 levels, suggesting the utility of GCN5 and its downstream effectors as therapeutic targets to either prevent or overcome tamoxifen resistance in breast cancer.

ACS Style

Ji Hoon Oh; Ji-Yeon Lee; Kwang H. Kim; Clara Yuri Kim; Da Som Jeong; Yejin Cho; Ki Taek Nam; Myoung Hee Kim. Elevated GCN5 expression confers tamoxifen resistance by upregulating AIB1 expression in ER-positive breast cancer. Cancer Letters 2020, 495, 145 -155.

AMA Style

Ji Hoon Oh, Ji-Yeon Lee, Kwang H. Kim, Clara Yuri Kim, Da Som Jeong, Yejin Cho, Ki Taek Nam, Myoung Hee Kim. Elevated GCN5 expression confers tamoxifen resistance by upregulating AIB1 expression in ER-positive breast cancer. Cancer Letters. 2020; 495 ():145-155.

Chicago/Turabian Style

Ji Hoon Oh; Ji-Yeon Lee; Kwang H. Kim; Clara Yuri Kim; Da Som Jeong; Yejin Cho; Ki Taek Nam; Myoung Hee Kim. 2020. "Elevated GCN5 expression confers tamoxifen resistance by upregulating AIB1 expression in ER-positive breast cancer." Cancer Letters 495, no. : 145-155.

Journal article
Published: 08 August 2020 in Toxics
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The compound 6:2 chlorinated polyfluorinated ether sulfonate (F-53B), a replacement for perfluorooctanesulfonate (PFOS) in the electroplating industry, has been widely detected in numerous environmental matrices, human sera, and organisms. Due to regulations that limit PFOS use, F-53B use is expected to increase. Therefore, in this study, we performed a subchronic oral toxicity study of F-53B in Sprague Dawley (SD) rats. F-53B was administered orally once daily to male and female rats for 28 days at doses of 5, 20, and 100 mg/kg/day. There were no toxicologically significant changes in F-53B-treated rats, except in the thyroid gland. However, F-53B slightly reduced the serum concentrations of thyroid hormones, including triiodothyronine and thyroxine, compared with their concentrations in the vehicle group. F-53B also induced follicular hyperplasia and was associated with increased thyroid hormone biosynthesis-associated protein expression. These results demonstrate that F-53B is a strong regulator of thyroid hormones in SD rats as it disrupts thyroid function. Thus, caution should be exercised in the industrial application of F-53B as an alternative for PFOS.

ACS Style

So-Hye Hong; Seung Hee Lee; Jun-Young Yang; Jin Hee Lee; Ki Kyung Jung; Ji Hyun Seok; Sung-Hee Kim; Ki Taek Nam; Jayoung Jeong; Jong Kwon Lee; Jae-Ho Oh. Orally Administered 6:2 Chlorinated Polyfluorinated Ether Sulfonate (F-53B) Causes Thyroid Dysfunction in Rats. Toxics 2020, 8, 54 .

AMA Style

So-Hye Hong, Seung Hee Lee, Jun-Young Yang, Jin Hee Lee, Ki Kyung Jung, Ji Hyun Seok, Sung-Hee Kim, Ki Taek Nam, Jayoung Jeong, Jong Kwon Lee, Jae-Ho Oh. Orally Administered 6:2 Chlorinated Polyfluorinated Ether Sulfonate (F-53B) Causes Thyroid Dysfunction in Rats. Toxics. 2020; 8 (3):54.

Chicago/Turabian Style

So-Hye Hong; Seung Hee Lee; Jun-Young Yang; Jin Hee Lee; Ki Kyung Jung; Ji Hyun Seok; Sung-Hee Kim; Ki Taek Nam; Jayoung Jeong; Jong Kwon Lee; Jae-Ho Oh. 2020. "Orally Administered 6:2 Chlorinated Polyfluorinated Ether Sulfonate (F-53B) Causes Thyroid Dysfunction in Rats." Toxics 8, no. 3: 54.

Journal article
Published: 06 March 2020 in Scientific Reports
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Engineered nucleases are widely used for creating frameshift or nonsense mutations in the target genes to eliminate gene functions. The resulting mRNAs carrying premature termination codons can be eliminated by nonsense-mediated mRNA decay. However, it is unclear how effective this process would be in vivo. Here, we found that the nonsense-mediated decay was unable to remove the mutant mRNAs in twelve out of sixteen homozygous mutant mice with frameshift mutations generated using engineered nucleases, which is far beyond what we expected. The frameshift mutant proteins translated by a single nucleotide deletion within the coding region were also detected in the p53 mutant mice. Furthermore, we showed that targeting the exons present downstream of the exons with a start codon or distant from ATG is relatively effective for eliminating mutant mRNAs in vivo, whereas the exons with a start codon are targeted to express the mutant mRNAs. Of the sixteen mutant mice generated, only four mutant mice targeting the downstream exons exhibited over 80% clearance of mutant mRNAs. Since the abnormal products, either mutant RNAs or mutant proteins, expressed by the target alleles might obscure the outcome of genome editing, these findings will provide insights in the improved performance of engineered nucleases when they are applied in vivo.

ACS Style

Jae Hoon Lee; Sungsook Yu; Tae Wook Nam; Jae-Il Roh; Young Jin; Jeong Pil Han; Ji-Young Cha; Yoon Ki Kim; Su-Cheong Yeom; Ki Taek Nam; Han-Woong Lee. The position of the target site for engineered nucleases improves the aberrant mRNA clearance in in vivo genome editing. Scientific Reports 2020, 10, 4173 -9.

AMA Style

Jae Hoon Lee, Sungsook Yu, Tae Wook Nam, Jae-Il Roh, Young Jin, Jeong Pil Han, Ji-Young Cha, Yoon Ki Kim, Su-Cheong Yeom, Ki Taek Nam, Han-Woong Lee. The position of the target site for engineered nucleases improves the aberrant mRNA clearance in in vivo genome editing. Scientific Reports. 2020; 10 (1):4173-9.

Chicago/Turabian Style

Jae Hoon Lee; Sungsook Yu; Tae Wook Nam; Jae-Il Roh; Young Jin; Jeong Pil Han; Ji-Young Cha; Yoon Ki Kim; Su-Cheong Yeom; Ki Taek Nam; Han-Woong Lee. 2020. "The position of the target site for engineered nucleases improves the aberrant mRNA clearance in in vivo genome editing." Scientific Reports 10, no. 1: 4173-9.

Journal article
Published: 05 December 2019 in International Journal of Molecular Sciences
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Peroxidasin (PXDN) is a unique peroxidase containing extracellular matrix motifs and stabilizes collagen IV networks by forming sulfilimine crosslinks. PXDN gene knockout in Caenorhabditis elegans (C. elegans) and Drosophila results in the demise at the embryonic and larval stages. PXDN mutations lead to severe eye disorders, including microphthalmia, cataract, glaucoma, and anterior segment dysgenesis in humans and mice. To investigate how PXDN loss of function affects organ development, we generated Pxdn knockout mice by deletion of exon 1 and its 5′ upstream sequences of the Pxdn gene using the CRISPR/Cas9 system. Loss of both PXDN expression and collagen IV sulfilimine cross-links was detected only in the homozygous mice, which showed completely or almost closed eyelids with small eyes, having no apparent external morphological defects in other organs. In histological analysis of eye tissues, the homozygous mice had extreme defects in eye development, including no eyeballs or drastically disorganized eye structures, whereas the heterozygous mice showed normal eye structure. Visual function tests also revealed no obvious functional abnormalities in the eyes between heterozygous mice and wild-type mice. Thus, these results suggest that PXDN activity is essential in eye development, and also indicate that a single allele of Pxdn gene is sufficient for eye-structure formation and normal visual function.

ACS Style

Hyun-Kyung Kim; Kyung A Ham; Seung-Woo Lee; Hong Seok Choi; Hong-Sug Kim; Hong Kyung Kim; Hae-Sol Shin; Kyoung Yul Seo; Yejin Cho; Ki Taek Nam; In-Beom Kim; Young Ae Joe. Biallelic Deletion of Pxdn in Mice Leads to Anophthalmia and Severe Eye Malformation. International Journal of Molecular Sciences 2019, 20, 6144 .

AMA Style

Hyun-Kyung Kim, Kyung A Ham, Seung-Woo Lee, Hong Seok Choi, Hong-Sug Kim, Hong Kyung Kim, Hae-Sol Shin, Kyoung Yul Seo, Yejin Cho, Ki Taek Nam, In-Beom Kim, Young Ae Joe. Biallelic Deletion of Pxdn in Mice Leads to Anophthalmia and Severe Eye Malformation. International Journal of Molecular Sciences. 2019; 20 (24):6144.

Chicago/Turabian Style

Hyun-Kyung Kim; Kyung A Ham; Seung-Woo Lee; Hong Seok Choi; Hong-Sug Kim; Hong Kyung Kim; Hae-Sol Shin; Kyoung Yul Seo; Yejin Cho; Ki Taek Nam; In-Beom Kim; Young Ae Joe. 2019. "Biallelic Deletion of Pxdn in Mice Leads to Anophthalmia and Severe Eye Malformation." International Journal of Molecular Sciences 20, no. 24: 6144.

Journal article
Published: 10 November 2019 in International Journal of Molecular Sciences
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Emerging evidence indicates that the activity of pyruvate kinase M2 (PKM2) isoform is crucial for the survival of tumor cells. However, the molecular mechanism underlying the function of PKM2 in renal cancer is undetermined. Here, we reveal the overexpression of PKM2 in the proximal tubule of renal tumor tissues from 70 cases of patients with renal carcinoma. The functional role of PKM2 in human renal cancer cells following small-interfering RNA-mediated PKM2 knockdown, which retarded 786-O cell growth was examined. Targeting PKM2 affected the protein kinase B (AKT)/mechanistic target of the rapamycin 1 (mTOR) pathway, and downregulated the expression of glycolytic enzymes, including lactate dehydrogenase A and glucose transporter-1, and other downstream signaling key proteins. PKM2 knockdown changed glycolytic metabolism, mitochondrial function, adenosine triphosphate (ATP) level, and intracellular metabolite formation and significantly reduced 786-O cell migration and invasion. Acridine orange and monodansylcadaverine staining, immunocytochemistry, and immunoblotting analyses revealed the induction of autophagy in renal cancer cells following PKM2 knockdown. This is the first study to indicate PKM2/AKT/mTOR as an important regulatory axis mediating the changes in the metabolism of renal cancer cells.

ACS Style

Prasanta Dey; Ji Yeon Son; Amit Kundu; Kyeong Seok Kim; Byung Mu Lee; Kyungsil Yoon; Ki Taek Nam. Knockdown of Pyruvate Kinase M2 Inhibits Cell Proliferation, Metabolism, and Migration in Renal Cell Carcinoma. International Journal of Molecular Sciences 2019, 20, 5622 .

AMA Style

Prasanta Dey, Ji Yeon Son, Amit Kundu, Kyeong Seok Kim, Byung Mu Lee, Kyungsil Yoon, Ki Taek Nam. Knockdown of Pyruvate Kinase M2 Inhibits Cell Proliferation, Metabolism, and Migration in Renal Cell Carcinoma. International Journal of Molecular Sciences. 2019; 20 (22):5622.

Chicago/Turabian Style

Prasanta Dey; Ji Yeon Son; Amit Kundu; Kyeong Seok Kim; Byung Mu Lee; Kyungsil Yoon; Ki Taek Nam. 2019. "Knockdown of Pyruvate Kinase M2 Inhibits Cell Proliferation, Metabolism, and Migration in Renal Cell Carcinoma." International Journal of Molecular Sciences 20, no. 22: 5622.

Journal article
Published: 02 September 2019 in International Journal of Molecular Sciences
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The main function of the skin is to protect the body from the external environment. The barrier function of the skin is mainly provided by the stratum corneum, which consists of corneocytes bound with the corneodesmosomes and lamellar lipids. Skin barrier proteins like loricrin and filaggrin also contribute to the skin barrier function. In various skin diseases, skin barrier dysfunction is a common symptom, and skin irritants like detergents or surfactants could also perturb skin barrier function. Many efforts have been made to develop strategies to improve skin barrier function. Here, we investigated whether the microfluidized lysates of Lactobacillus rhamnosus (LR), one of the most widely used probiotic species for various health benefits, may improve the skin barrier function in a reconstructed human epidermis, Keraskin™. Application of LR lysate on Keraskin™ increased the expression of tight junction proteins; claudin 1 and occludin as determined by immunofluorescence analysis, and skin barrier proteins; loricrin and filaggrin as determined by immunohistochemistry and immunofluorescence analysis and qPCR. Also, the cytotoxicity of a skin irritant, sodium lauryl sulfate (SLS), was alleviated by the pretreatment of LR lysate. The skin barrier protective effects of LR lysate could be further demonstrated by the attenuation of SLS-enhanced dye-penetration. LR lysate also attenuated the destruction of desmosomes after SLS treatment. Collectively, we demonstrated that LR lysate has protective effects on the skin barrier, which could expand the utility of probiotics to skin-moisturization ingredients.

ACS Style

Ye-On Jung; Haengdueng Jeong; Yejin Cho; Eun-Ok Lee; Hye-Won Jang; Jinwook Kim; Ki Taek Nam; Kyung-Min Lim. Lysates of a Probiotic, Lactobacillus rhamnosus, Can Improve Skin Barrier Function in a Reconstructed Human Epidermis Model. International Journal of Molecular Sciences 2019, 20, 4289 .

AMA Style

Ye-On Jung, Haengdueng Jeong, Yejin Cho, Eun-Ok Lee, Hye-Won Jang, Jinwook Kim, Ki Taek Nam, Kyung-Min Lim. Lysates of a Probiotic, Lactobacillus rhamnosus, Can Improve Skin Barrier Function in a Reconstructed Human Epidermis Model. International Journal of Molecular Sciences. 2019; 20 (17):4289.

Chicago/Turabian Style

Ye-On Jung; Haengdueng Jeong; Yejin Cho; Eun-Ok Lee; Hye-Won Jang; Jinwook Kim; Ki Taek Nam; Kyung-Min Lim. 2019. "Lysates of a Probiotic, Lactobacillus rhamnosus, Can Improve Skin Barrier Function in a Reconstructed Human Epidermis Model." International Journal of Molecular Sciences 20, no. 17: 4289.

Journal article
Published: 01 August 2019 in Scientific Reports
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P16Ink4a/CDKN2A is a tumor suppressor that critically regulates the cell cycle. Indeed, p16Ink4a deficiency promotes tumor formation in various tissues. We now report that p16Ink4a deficiency in female mice, but not male mice, induces leanness especially in old age, as indicated by lower body weight and smaller white adipose tissue, although other major organs are unaffected. Unexpectedly, the integrity, number, and sizes of adipocytes in white adipose tissue were unaffected, as was macrophage infiltration. Hence, hypermobility appeared to be accountable for the phenotype, since food consumption was not altered. Histological analysis of the cerebellum and deep cerebellar nuclei, a vital sensorimotor control center, revealed increased proliferation of neuronal cells and improved cerebellum integrity. Expression of estrogen receptor β (ERβ) and PCNA also increased in deep cerebellar nuclei, implying crosstalk between p16Ink4a and ERβ. Furthermore, p16Ink4a deficiency expands LC3B+ cells and GFAP+ astrocytes in response to estrogen. Collectively, the data suggest that loss of p16INK4a induces sexually dimorphic leanness in female mice, which appears to be due to protection against cerebellar senescence by promoting neuronal proliferation and homeostasis via ERβ.

ACS Style

Kwang H. Kim; Yejin Cho; Jaehoon Lee; Haengdueng Jeong; Yura Lee; Soo In Kim; Chang-Hoon Kim; Han-Woong Lee; Ki Taek Nam. Sexually dimorphic leanness and hypermobility in p16Ink4a/CDKN2A-deficient mice coincides with phenotypic changes in the cerebellum. Scientific Reports 2019, 9, 1 -10.

AMA Style

Kwang H. Kim, Yejin Cho, Jaehoon Lee, Haengdueng Jeong, Yura Lee, Soo In Kim, Chang-Hoon Kim, Han-Woong Lee, Ki Taek Nam. Sexually dimorphic leanness and hypermobility in p16Ink4a/CDKN2A-deficient mice coincides with phenotypic changes in the cerebellum. Scientific Reports. 2019; 9 (1):1-10.

Chicago/Turabian Style

Kwang H. Kim; Yejin Cho; Jaehoon Lee; Haengdueng Jeong; Yura Lee; Soo In Kim; Chang-Hoon Kim; Han-Woong Lee; Ki Taek Nam. 2019. "Sexually dimorphic leanness and hypermobility in p16Ink4a/CDKN2A-deficient mice coincides with phenotypic changes in the cerebellum." Scientific Reports 9, no. 1: 1-10.

Original paper
Published: 29 May 2019 in The Journal of Pathology
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Rab25 can function as both a tumor suppressor and a tumor promoter across different tissues. This study sought to clarify the role of Rab25 as a tumor suppressor in skin squamous cell carcinoma (SCC). Rab25 loss was closely associated with neoplastic transition in both humans and mice. Rab25 loss was well correlated with increased cell proliferation and poor differentiation in human SCC. While Rab25 knockout (KO) in mice did not induce spontaneous tumor formation, it did significantly accelerate tumor generation and promote malignant transformation in a mouse two‐stage skin carcinogenesis model. Xenografting of a Rab25‐deficient human keratinocyte cell line, HaCaT, also elicited neoplastic transformation. Notably, Rab25 deficiency led to dysregulation of integrins β1, β4, and α6, which matched well with increased epidermal proliferation and impaired desmosome–tight junction formation. Rab25 deficiency induced impairment of integrin recycling, leading to the improper expression of integrins. In line with this, significant attenuation of integrin β1, β4, and α6 expression was identified in human SCCs where Rab25 was deficient. Collectively, these results suggest that loss of Rab25 promotes the development and neoplastic transition of SCC through dysregulation of integrin trafficking. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

ACS Style

Haengdueng Jeong; Kyung‐Min Lim; Kwang H Kim; Yejin Cho; Buhyun Lee; Byron C Knowles; Joseph T Roland; Jeffrey P Zwerner; James R Goldenring; Ki Taek Nam. Loss of Rab25 promotes the development of skin squamous cell carcinoma through the dysregulation of integrin trafficking. The Journal of Pathology 2019, 249, 227 -240.

AMA Style

Haengdueng Jeong, Kyung‐Min Lim, Kwang H Kim, Yejin Cho, Buhyun Lee, Byron C Knowles, Joseph T Roland, Jeffrey P Zwerner, James R Goldenring, Ki Taek Nam. Loss of Rab25 promotes the development of skin squamous cell carcinoma through the dysregulation of integrin trafficking. The Journal of Pathology. 2019; 249 (2):227-240.

Chicago/Turabian Style

Haengdueng Jeong; Kyung‐Min Lim; Kwang H Kim; Yejin Cho; Buhyun Lee; Byron C Knowles; Joseph T Roland; Jeffrey P Zwerner; James R Goldenring; Ki Taek Nam. 2019. "Loss of Rab25 promotes the development of skin squamous cell carcinoma through the dysregulation of integrin trafficking." The Journal of Pathology 249, no. 2: 227-240.

Journal article
Published: 27 February 2019 in Scientific Reports
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Breast cancer metastasis accounts for most of the deaths from breast cancer. Since epithelial-mesenchymal transition (EMT) plays an important role in promoting metastasis of cancer, many mechanisms regarding EMT have been studied. We previously showed that Ribonucleic acid export 1 (RAE1) is dysregulated in breast cancer and its overexpression leads to aggressive breast cancer phenotypes by inducing EMT. Here, we evaluated the functional capacity of RAE1 in breast cancer metastasis by using a three-dimensional (3D) culture system and xenograft models. Furthermore, to investigate the mechanisms of RAE1-driven EMT, in vitro studies were carried out. The induction of EMT with RAE1-overexpression was confirmed under the 3D culture system and in vivo system. Importantly, RAE1 mediates upregulation of an EMT marker ZEB1, by binding to the promoter region of ZEB1. Knockdown of ZEB1 in RAE1-overexpressing cells suppressed invasive and migratory behaviors, accompanied by an increase in epithelial and a decrease in mesenchymal markers. Taken together, these data demonstrate that RAE1 contributes to breast cancer metastasis by regulating a key EMT-inducing factor ZEB1 expression, suggesting its potential as a therapeutic target.

ACS Style

Ji Hoon Oh; Ji-Yeon Lee; Sungsook Yu; Yejin Cho; Sumin Hur; Ki Taek Nam; Myoung Hee Kim. RAE1 mediated ZEB1 expression promotes epithelial–mesenchymal transition in breast cancer. Scientific Reports 2019, 9, 2977 .

AMA Style

Ji Hoon Oh, Ji-Yeon Lee, Sungsook Yu, Yejin Cho, Sumin Hur, Ki Taek Nam, Myoung Hee Kim. RAE1 mediated ZEB1 expression promotes epithelial–mesenchymal transition in breast cancer. Scientific Reports. 2019; 9 (1):2977.

Chicago/Turabian Style

Ji Hoon Oh; Ji-Yeon Lee; Sungsook Yu; Yejin Cho; Sumin Hur; Ki Taek Nam; Myoung Hee Kim. 2019. "RAE1 mediated ZEB1 expression promotes epithelial–mesenchymal transition in breast cancer." Scientific Reports 9, no. 1: 2977.

Journal article
Published: 01 February 2018 in Toxicology in Vitro
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Ionic liquids have gained increasing attention in the chemical industry as potential green substitutes for traditional solvents. However, little is known about toxicity of ionic liquids on the skin, a major exposure portal to toxic substances. Here, we evaluated dermal toxicity of ionic liquids using human keratinocyte and fibroblast cell line, 3D reconstructed human epidermis, and full-thickness model to investigate underlying mechanisms. Cytotoxicity of ionic liquids was evaluated for representative anions, [TFSI], [PF6], [BF4], and [DCA], as well as for cations, [EMIM], [BMPY], [TBA] and [Zn], in human keratinocyte cell line, HaCaT, and human dermal fibroblasts. In our results, significant cytotoxicity was induced by ionic liquids with [TFSI] in both cell lines. Notably, cytotoxicity of [TFSI] containing ionic liquids was comparable to xylene, a toxic conventional organic solvent. Fluorescent and flow cytometric analysis revealed that [TFSI]-exposed cells underwent necrotic cell death. Reactive oxygen species (ROS) was increased while the amount of glutathione was decreased by [TFSI] in dose-dependent manner, which was reversed by antioxidant, N-acetylcysteine. In 3D reconstructed human epidermis and full-thickness model, a single application of [TFSI] induced toxicity although it was minimal and largely limited to epidermal layer. Collectively, these results demonstrated potential dermal toxicity of ionic liquids.

ACS Style

Jee-Hyun Hwang; Hyeonji Park; Dal Woong Choi; Ki Taek Nam; Kyung-Min Lim. Investigation of dermal toxicity of ionic liquids in monolayer-cultured skin cells and 3D reconstructed human skin models. Toxicology in Vitro 2018, 46, 194 -202.

AMA Style

Jee-Hyun Hwang, Hyeonji Park, Dal Woong Choi, Ki Taek Nam, Kyung-Min Lim. Investigation of dermal toxicity of ionic liquids in monolayer-cultured skin cells and 3D reconstructed human skin models. Toxicology in Vitro. 2018; 46 ():194-202.

Chicago/Turabian Style

Jee-Hyun Hwang; Hyeonji Park; Dal Woong Choi; Ki Taek Nam; Kyung-Min Lim. 2018. "Investigation of dermal toxicity of ionic liquids in monolayer-cultured skin cells and 3D reconstructed human skin models." Toxicology in Vitro 46, no. : 194-202.

Journal article
Published: 01 April 2017 in Biomaterials
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The development of multifunctional reagents for simultaneous specific near-infrared (NIR) imaging and phototherapy of tumors is of great significance. This work describes the design of a cathepsin B-activated fluorescent probe (CyA-P-CyB) and its applications as an NIR imaging probe for tumor cells and as a phototherapy reagent for tumors. In vitro experiments demonstrated that CyA-P-CyB was activated via the cleavage of a peptide linker by cathepsin B in tumor cells to produce fluorescence in the NIR region based on a FRET mechanism. MTT assays showed that the phototoxicity of CyA-P-CyB toward cells depended on the activity of cathepsin B, and the probe exhibited specific phototoxicity toward tumor cells. CyA-P-CyB was also successfully applied to the in vivo imaging and phototherapy of tumors. Histological analysis indicated that CyA-P-CyB had no cytotoxic effects on seven mouse tissues (lung, liver, heart, kidney, pancreas, spleen and brain) after the CyA-P-CyB treatment and laser irradiation.

ACS Style

Xiaoqiang Chen; Dayoung Lee; Sungsook Yu; Gyoungmi Kim; Songyi Lee; Yejin Cho; Haengdueng Jeong; Ki Taek Nam; Juyoung Yoon. In vivo near-infrared imaging and phototherapy of tumors using a cathepsin B-activated fluorescent probe. Biomaterials 2017, 122, 130 -140.

AMA Style

Xiaoqiang Chen, Dayoung Lee, Sungsook Yu, Gyoungmi Kim, Songyi Lee, Yejin Cho, Haengdueng Jeong, Ki Taek Nam, Juyoung Yoon. In vivo near-infrared imaging and phototherapy of tumors using a cathepsin B-activated fluorescent probe. Biomaterials. 2017; 122 ():130-140.

Chicago/Turabian Style

Xiaoqiang Chen; Dayoung Lee; Sungsook Yu; Gyoungmi Kim; Songyi Lee; Yejin Cho; Haengdueng Jeong; Ki Taek Nam; Juyoung Yoon. 2017. "In vivo near-infrared imaging and phototherapy of tumors using a cathepsin B-activated fluorescent probe." Biomaterials 122, no. : 130-140.

Journal article
Published: 11 June 2015 in The American Journal of Pathology
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Doublecortin-like kinase 1 (Dclk1) is considered a reliable marker for tuft cells in the gastrointestinal tract. We investigated the dynamic changes of tuft cells associated with mouse models of oxyntic atrophy and metaplasia in the stomach. Increases in the numbers of Dclk1-positive tuft cells were observed in several models of parietal cell loss. However, the expanded population of Dclk1-expressing cells showed a morphologically distinct structure in apical microvilli and acetylated microtubules, which was not seen in the tuft cells present in the normal gastric mucosa. These microvillar sensory cells (MVSCs) showed no evidence of proliferation. The expansion of the MVSCs induced by oxyntic atrophy was reversible after the return of parietal cells. More important, expansion of MVSCs after induced parietal cell loss was not observed in Gast(-/-) mice. Although the Dclk1-expressing cells in the normal gastric mucosa were in part derived from Lrig1-expressing stem cells, the Lrig1-lineaged cells did not produce the expanded Dclk1-expressing cells associated with oxyntic atrophy. These studies indicate that loss of parietal cells leads to the reversible emergence of a novel Dclk1-expressing sensory cell population in the gastric mucosa.

ACS Style

Eunyoung Choi; Christine P. Petersen; Lynne A. Lapierre; Janice A. Williams; Victoria Weis; James R. Goldenring; Ki Taek Nam. Dynamic expansion of gastric mucosal doublecortin-like kinase 1-expressing cells in response to parietal cell loss is regulated by gastrin. The American Journal of Pathology 2015, 185, 2219 -31.

AMA Style

Eunyoung Choi, Christine P. Petersen, Lynne A. Lapierre, Janice A. Williams, Victoria Weis, James R. Goldenring, Ki Taek Nam. Dynamic expansion of gastric mucosal doublecortin-like kinase 1-expressing cells in response to parietal cell loss is regulated by gastrin. The American Journal of Pathology. 2015; 185 (8):2219-31.

Chicago/Turabian Style

Eunyoung Choi; Christine P. Petersen; Lynne A. Lapierre; Janice A. Williams; Victoria Weis; James R. Goldenring; Ki Taek Nam. 2015. "Dynamic expansion of gastric mucosal doublecortin-like kinase 1-expressing cells in response to parietal cell loss is regulated by gastrin." The American Journal of Pathology 185, no. 8: 2219-31.

Review
Published: 01 January 2014 in Journal of Gastric Cancer
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Gastric cancer is one of the most common cancers in the world. Animal models have been used to elucidate the details of the molecular mechanisms of various cancers. However, most inbred strains of mice have resistance to gastric carcinogenesis. Helicobacter infection and carcinogen treatment have been used to establish mouse models that exhibit phenotypes similar to those of human gastric cancer. A large number of transgenic and knockout mouse models of gastric cancer have been developed using genetic engineering. A combination of carcinogens and gene manipulation has been applied to facilitate development of advanced gastric cancer; however, it is rare for mouse models of gastric cancer to show aggressive, metastatic phenotypes required for preclinical studies. Here, we review current mouse models of gastric carcinogenesis and provide our perspectives on future developments in this field.

ACS Style

Sungsook Yu; Mijeong Yang; Ki Taek Nam. Mouse Models of Gastric Carcinogenesis. Journal of Gastric Cancer 2014, 14, 67 -86.

AMA Style

Sungsook Yu, Mijeong Yang, Ki Taek Nam. Mouse Models of Gastric Carcinogenesis. Journal of Gastric Cancer. 2014; 14 (2):67-86.

Chicago/Turabian Style

Sungsook Yu; Mijeong Yang; Ki Taek Nam. 2014. "Mouse Models of Gastric Carcinogenesis." Journal of Gastric Cancer 14, no. 2: 67-86.