@article{jin_ibrahim_magness_blikslager_2018, title={Knockout of ClC-2 reveals critical functions of adherens junctions in colonic homeostasis and tumorigenicity}, volume={315}, ISSN={0193-1857 1522-1547}, url={http://dx.doi.org/10.1152/ajpgi.00087.2018}, DOI={10.1152/ajpgi.00087.2018}, abstractNote={Adherens junctions (AJs), together with tight junctions (TJs), form an apical junctional complex that regulates intestinal epithelial cell-to-cell adherence and barrier homeostasis. Within the AJ, membrane-bound E-cadherin binds β-catenin, which functions as an essential intracellular signaling molecule. We have previously identified a novel protein in the region of the apical junction complex, chloride channel protein-2 (ClC-2), that we have used to study TJ regulation. In this study, we investigated the possible effects of ClC-2 on the regulation of AJs in intestinal mucosal epithelial homeostasis and tumorigenicity. Mucosal homeostasis and junctional proteins were examined in wild-type (WT) and ClC-2 knockout (KO) mice as well as associated colonoids. Tumorigenicity and AJ-associated signaling were evaluated in a murine colitis-associated tumor model and in a colorectal cancer cell line (HT-29). Colonic tissues from ClC-2 KO mice had altered ultrastructural morphology of intercellular junctions with reduced colonocyte differentiation, whereas jejunal tissues had minimal changes. Colonic crypts from ClC-2 KO mice had significantly higher numbers of less-differentiated forms of colonoids compared with WT. Furthermore, the absence of ClC-2 resulted in redistribution of AJ proteins and increased β-catenin activity. Downregulation of ClC-2 in colorectal cells resulted in significant increases in proliferation associated with disruption of AJs. Colitis-associated tumors in ClC-2 KO mice were significantly increased, associated with β-catenin transcription factor activation. The absence of ClC-2 results in less differentiated colonic crypts and increased tumorigenicity associated with colitis via dysregulation of AJ proteins and activation of β-catenin-associated signaling.}, number={6}, journal={American Journal of Physiology-Gastrointestinal and Liver Physiology}, publisher={American Physiological Society}, author={Jin, Younggeon and Ibrahim, Dina and Magness, Scott T. and Blikslager, Anthony T.}, year={2018}, month={Dec}, pages={G966–G979} }
 @article{shin_ferguson_2017, title={Exploring Product Solution Differences Due to Choice Model Selection in the Presence of Noncompensatory Decisions With Conjunctive Screening Rules}, volume={139}, ISSN={["1050-0472"]}, DOI={10.1115/1.4035051}, abstractNote={Research in market-based product design has often used compensatory preference models that assume an additive part-worth rule. These additive models have a simple, usable form and their parameters can be estimated using existing software packages. However, marketing research literature has demonstrated that consumers sometimes use noncompensatory-derived heuristics to simplify their choice decisions. This paper explores the quality of optimal solution obtained to a product line design search when using a compensatory model in the presence of noncompensatory choices and a noncompensatory model with conjunctive screening rules. Motivation for this work comes from the challenges posed by Bayesian-based noncompensatory models: the need for screening rule assumptions, probabilistic representations of noncompensatory choices, and discontinuous choice probability functions. This paper demonstrates how respondents making noncompensatory choices with conjunctive rules can lead to compensatory model estimations with distinct respondent segmentation and relative, large absolute part-worth values. Results from a product design problem suggest that using a compensatory model can provide benefits of smaller design errors and reduced computational costs. Product design optimization problems using real choice data confirm that the compensatory model and the noncompensatory model with conjunctive rules provide comparable solutions that have similar likelihoods of not being screened out when using a consideration set verifier. While many different noncompensatory heuristic rules exist, the presented study is limited to conjunctive screening rules.}, number={2}, journal={JOURNAL OF MECHANICAL DESIGN}, author={Shin, Jaekwan and Ferguson, Scott}, year={2017}, month={Feb} }
 @article{jin_blikslager_2016, title={Myosin light chain kinase mediates intestinal barrier dysfunction via occludin endocytosis during anoxia/reoxygenation injury}, volume={311}, ISSN={0363-6143 1522-1563}, url={http://dx.doi.org/10.1152/ajpcell.00113.2016}, DOI={10.1152/ajpcell.00113.2016}, abstractNote={Intestinal anoxia/reoxygenation (A/R) injury induces loss of barrier function followed by epithelial repair. Myosin light chain kinase (MLCK) has been shown to alter barrier function via regulation of interepithelial tight junctions, but has not been studied in intestinal A/R injury. We hypothesized that A/R injury would disrupt tight junction barrier function via MLCK activation and myosin light chain (MLC) phosphorylation. Caco-2BBe1 monolayers were subjected to anoxia for 2 h followed by reoxygenation in 21% O2, after which barrier function was determined by measuring transepithelial electrical resistance (TER) and FITC-dextran flux. Tight junction proteins and MLCK signaling were assessed by Western blotting, real-time PCR, or immunofluorescence microscopy. The role of MLCK was further investigated with select inhibitors (ML-7 and peptide 18) by using in vitro and ex vivo models. Following A/R injury, there was a significant increase in paracellular permeability compared with control cells, as determined by TER and dextran fluxes ( P < 0.05). The tight junction protein occludin was internalized during A/R injury and relocalized to the region of the tight junction after 4 h of recovery. MLC phosphorylation was significantly increased by A/R injury ( P < 0.05), and treatment with the MLCK inhibitor peptide 18 attenuated the increased epithelial monolayer permeability and occludin endocytosis caused by A/R injury. Application of MLCK inhibitors to ischemia-injured porcine ileal mucosa induced significant increases in TER and reduced mucosal-to-serosal fluxes of3H-labeled mannitol. These data suggest that MLCK-induced occludin endocytosis mediates intestinal epithelial barrier dysfunction during A/R injury. Our results also indicate that MLCK-dependent occludin regulation may be a target for the therapeutic treatment of ischemia/reperfusion injury.}, number={6}, journal={American Journal of Physiology-Cell Physiology}, publisher={American Physiological Society}, author={Jin, Younggeon and Blikslager, Anthony T.}, year={2016}, month={Dec}, pages={C996–C1004} }
 @article{kim_jin_jin_yang_joo_lee_shim_kim_yoo_lee_et al._2015, title={Anticancer activity of TTAC-0001, a fully human anti-vascular endothelial growth factor receptor 2 (VEGFR-2/KDR) monoclonal antibody, is associated with inhibition of tumor angiogenesis}, volume={7}, DOI={10.1080/19420862.2015.1086854}, abstractNote={Vascular endothelial growth factor (VEGF) and its receptors are considered the primary cause of tumor-induced angiogenesis. Specifically, VEGFR-2/kinase insert domain receptor (KDR) is part of the major signaling pathway that plays a significant role in tumor angiogenesis, which is associated with the development of various types of tumor and metastasis. In particular, KDR is involved in tumor angiogenesis as well as cancer cell growth and survival. In this study, we evaluated the therapeutic potential of TTAC-0001, a fully human antibody against VEGFR-2/KDR. To assess the efficacy of the antibody and pharmacokinetic (PK) relationship in vivo, we tested the potency of TTAC-0001 in glioblastoma and colorectal cancer xenograft models. Antitumor activity of TTAC-0001 in preclinical models correlated with tumor growth arrest, induction of tumor cell apoptosis, and inhibition of angiogenesis. We also evaluated the combination effect of TTAC-0001 with a chemotherapeutic agent in xenograft models. We were able to determine the relationship between PK and the efficacy of TTAC-0001 through in vivo single-dose PK study. Taken together, our data suggest that targeting VEGFR-2 with TTAC-0001 could be a promising approach for cancer treatment.}, number={6}, journal={mAbs}, publisher={Informa UK Limited}, author={Kim, Dong Geon and Jin, Younggeon and Jin, Juyoun and Yang, Heekyoung and Joo, Kyeung Min and Lee, Weon Sup and Shim, Sang Ryeol and Kim, Sung-Woo and Yoo, Jinsang and Lee, Sang Hoon and et al.}, year={2015}, month={Aug}, pages={1195–1204} }
 @article{jin_pridgen_blikslager_2015, title={Pharmaceutical Activation or Genetic Absence of ClC-2 Alters Tight Junctions During Experimental Colitis}, volume={21}, ISSN={1078-0998}, url={http://dx.doi.org/10.1097/MIB.0000000000000550}, DOI={10.1097/mib.0000000000000550}, abstractNote={Background:We have previously reported that the ClC-2 chloride channel has an important role in regulation of tight junction barrier function during experimental colitis, and the pharmaceutical ClC-2 activator lubiprostone initiates intestinal barrier repair in ischemic-injured intestine. Thus, we hypothesized that pharmaceutical ClC-2 activation would have a protective and therapeutic effect in murine models of colitis, which would be absent in ClC-2−/− mice. Methods:We administered lubiprostone to wild-type or ClC-2−/− mice with dextran sulfate sodium (DSS) or 2, 4, 5-trinitrobenzene sulfonic acid–induced colitis. We determined the severity of colitis and assessed intestinal permeability. Selected tight junction proteins were analyzed by Western blotting and immunofluorescence/confocal microscopy, whereas proliferative and differentiated cells were examined with special staining and immunohistochemistry. Results:Oral preventive or therapeutic administration of lubiprostone significantly reduced the severity of colitis and reduced intestinal permeability in both DSS and trinitrobenzene sulfonic acid–induced colitis. Preventive treatment with lubiprostone induced significant recovery of the expression and distribution of selected sealing tight junction proteins in mice with DSS-induced colitis. In addition, lubiprostone reduced crypt proliferation and increased the number of differentiated epithelial cells. Alternatively, when lubiprostone was administered to ClC-2−/− mice, the protective effect against DSS colitis was limited. Conclusions:This study suggests a central role for ClC-2 in restoration of barrier function and tight junction architecture in experimental murine colitis, which can be therapeutically targeted with lubiprostone.}, number={12}, journal={Inflammatory Bowel Diseases}, publisher={Oxford University Press (OUP)}, author={Jin, Younggeon and Pridgen, Tiffany A. and Blikslager, Anthony T.}, year={2015}, month={Dec}, pages={2747–2757} }
 @article{lee_pyun_kim_shim_nam_yoo_jin_jin_kwon_yun_et al._2015, title={TTAC-0001, a human monoclonal antibody targeting VEGFR-2/KDR, blocks tumor angiogenesis}, volume={7}, DOI={10.1080/19420862.2015.1045168}, abstractNote={Angiogenesis is one of the most important processes for cancer cell survival, tumor growth and metastasis. Vascular endothelial growth factor (VEGF) and its receptor, particularly VEGF receptor-2 (VEGFR-2, or kinase insert domain-containing receptor, KDR), play critical roles in tumor-associated angiogenesis. We developed TTAC-0001, a human monoclonal antibody against VEGFR-2/KDR from a fully human naïve single-chain variable fragment phage library. TTAC-0001 was selected as a lead candidate based on its affinity, ligand binding inhibition and inhibition of VEGFR-2 signal in human umbilical vein endothelial cells (HUVEC). TTAC-0001 inhibited binding of VEGF-C and VEGF-D to VEGFR-2 in addition to VEGF-A. It binds on the N-terminal regions of domain 2 and domain 3 of VEGFR-2. It could inhibit the phosphorylation of VEGFR-2/KDR and ERK induced by VEGF in HUVEC. TTAC-0001 also inhibited VEGF-mediated endothelial cell proliferation, migration and tube formation in vitro, as well as ex vivo vessel sprouting from rat aortic rings and neovascularization in mouse matrigel model in vivo. Our data indicates that TTAC-0001 blocks the binding of VEGFs to VEGFR-2/KDR and inhibits VEGFR-induced signaling pathways and angiogenesis. Therefore, these data strongly support the further development of TTAC-0001 as an anti-cancer agent in the clinic.}, number={5}, journal={mAbs}, publisher={Informa UK Limited}, author={Lee, Weon Sup and Pyun, Bo-Jeong and Kim, Sung-Woo and Shim, Sang Ryeol and Nam, Ju Ryoung and Yoo, Ji Young and Jin, Younggeon and Jin, Juyoun and Kwon, Young-Guen and Yun, Chae-Ok and et al.}, year={2015}, month={May}, pages={957–968} }
 @article{jin_pridgen_blikslager_2014, title={Tu2028 Lubiprostone reduces murine colitis principally in a ClC-2-dependent manner.}, volume={146}, ISSN={0016-5085}, url={http://dx.doi.org/10.1016/S0016-5085(14)63275-3}, DOI={10.1016/s0016-5085(14)63275-3}, number={5}, journal={Gastroenterology}, publisher={Elsevier BV}, author={Jin, Younggeon and Pridgen, Tiffany and Blikslager, Anthony}, year={2014}, month={May}, pages={S-901} }
 @article{lee_seol_lee_kang_kang_jin_jo_jin_lee_joo_et al._2013, title={Gene silencing of c-Met leads to brain metastasis inhibitory effects}, volume={30}, DOI={10.1007/s10585-013-9584-7}, number={7}, journal={Clin Exp Metastasis}, publisher={Springer Science \mathplus Business Media}, author={Lee, Se Jeong and Seol, Ho Jun and Lee, Hye Won and Kang, Won Young and Kang, Bong Gu and Jin, Juyoun and Jo, Mi-Young and Jin, Younggeon and Lee, Jung-Il and Joo, Kyeung Min and et al.}, year={2013}, month={Apr}, pages={845–854} }
 @article{jin_jin_yang_park_lee_kim_shim_kim_lee_yoo_et al._2011, title={Abstract 647: TTAC-0001, anti-VEGFR2/KDR monoclonal antibody, inhibits VEGFR signaling and tumor growth in preclinical models}, volume={71}, DOI={10.1158/1538-7445.am2011-647}, abstractNote={Abstract}, number={8 Supplement}, journal={Cancer Res}, publisher={American Association for Cancer Research (AACR)}, author={Jin, Younggeon and Jin, Juyoun and Yang, Heekyoung and Park, Minjae and Lee, Weon Sup and Kim, Sung-Woo and Shim, Sang Ryeol and Kim, Yeonjoo and Lee, Sang Hoon and Yoo, Jin-San and et al.}, year={2011}, month={Apr}, pages={647–647} }
 @article{lee_jin_jin_kang_nam_joo_cha_2011, title={Functional neural stem cell isolation from brains of adult mutant SOD1 (SOD1 G93A ) transgenic amyotrophic lateral sclerosis (ALS) mice}, volume={33}, DOI={10.1179/016164110x12807570509899}, abstractNote={Abstract  Objectives: The aim of present study is to investigate more functional neural stem cells (NSCs) could be isolated from brains with amyotrophic lateral sclerosis (ALS) and expanded in vitro, based on previous reports demonstrating de novo neurogenesis is enhanced to replace degenerating neural tissue. Methods: Thirteen- or eighteen-week-old mutant human Cu/Zn superoxide dismutase (SOD1G93A) transgenic ALS and wild-type SOD1 transgenic control mice were utilized. Changes in numbers of NSCs in the dentate gyrus were analyzed by immunohistochemistry against nestin and CD133. NSCs were primarily cultured from hippocampus of ALS or control mice. Expression of NSC markers, in vitro expansion capacity, and differentiating potential were compared. Results: Hippocampus of 13-week-old pre-symptomatic ALS mice harbor more cells that can be propagated for more than 12 passages in vitro, compared with same age control mice. Primarily-cultured cells formed neurospheres in the NSC culture medium, expressed NSC markers, and differentiated into cells with differentiated neural cell characteristics in the differentiation condition confirming that they are NSCs. In contrast, long-term expansible NSCs could not be derived from brains of 18-week-old symptomatic ALS mice with the same experimental techniques, although they had comparable nestin-immunoreactive cells in the dentate gyrus. Discussion: These results would suggest that increased neuroregeneration in early phase of ALS could be translated to regenerative approaches; however, long-term exposure to ALS microenvironments could abolish functional capacities of NSCs.}, number={1}, journal={Neurological Research}, publisher={Maney Publishing}, author={Lee, Jae Chul and Jin, Younggeon and Jin, Juyoun and Kang, Bong Gu and Nam, Do-Hyun and Joo, Kyeung Min and Cha, Choong Ik}, year={2011}, month={Jan}, pages={33–37} }
 @article{jin_jin_joo_lee_jo_kim_nam_2010, title={Abstract LB-326: Synergistic therapeutic effects of cytokine-induced killer (CIK) cell and temozolomide against glioblastoma}, volume={70}, DOI={10.1158/1538-7445.am10-lb-326}, abstractNote={Abstract}, number={8 Supplement}, journal={Cancer Res}, publisher={American Association for Cancer Research (AACR)}, author={Jin, Younggeon and Jin, Juyoun and Joo, Kyeung Min and Lee, Se Jeong and Jo, Mi-young and Kim, Yonghyun and Nam, Do-Hyun}, year={2010}, month={Apr}, pages={LB-326-LB-326} }