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2. Mitochondrial volume fraction and translation duration impact mitochondrial mRNA localization and protein synthesis.

Author

Tsuboi, Tatsuhisa, Viana, Matheus P, Xu, Fan, Yu, Jingwen, Chanchani, Raghav, Arceo, Ximena G, Tutucci, Evelina, Choi, Joonhyuk, Chen, Yang S, Singer, Robert H, Rafelski, Susanne M, and Zid, Brian M

Subjects
S. cerevisiae, cell biology, chromosomes, gene expression, mRNA localization, mitochondria, protein synthesis, Biochemistry and Cell Biology
Abstract

Mitochondria are dynamic organelles that must precisely control their protein composition according to cellular energy demand. Although nuclear-encoded mRNAs can be localized to the mitochondrial surface, the importance of this localization is unclear. As yeast switch to respiratory metabolism, there is an increase in the fraction of the cytoplasm that is mitochondrial. Our data point to this change in mitochondrial volume fraction increasing the localization of certain nuclear-encoded mRNAs to the surface of the mitochondria. We show that mitochondrial mRNA localization is necessary and sufficient to increase protein production to levels required during respiratory growth. Furthermore, we find that ribosome stalling impacts mRNA sensitivity to mitochondrial volume fraction and counterintuitively leads to enhanced protein synthesis by increasing mRNA localization to mitochondria. This points to a mechanism by which cells are able to use translation elongation and the geometric constraints of the cell to fine-tune organelle-specific gene expression through mRNA localization.

Published
2020

5. AI-driven robotic chemist for autonomous synthesis of organic molecules

Author

Ha, Taesin, primary, Lee, Dongseon, additional, Kwon, Youngchun, additional, Park, Min Sik, additional, Lee, Sangyoon, additional, Jang, Jaejun, additional, Choi, Byungkwon, additional, Jeon, Hyunjeong, additional, Kim, Jeonghun, additional, Choi, Hyundo, additional, Seo, Hyung-Tae, additional, Choi, Wonje, additional, Hong, Wooram, additional, Park, Young Jin, additional, Jang, Junwon, additional, Cho, Joonkee, additional, Kim, Bosung, additional, Kwon, Hyukju, additional, Kim, Gahee, additional, Oh, Won Seok, additional, Kim, Jin Woo, additional, Choi, Joonhyuk, additional, Min, Minsik, additional, Jeon, Aram, additional, Jung, Yongsik, additional, Kim, Eunji, additional, Lee, Hyosug, additional, and Choi, Youn-Suk, additional

Published
2023
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8. Systematic mapping of TF-mediated cell fate changes by a pooled induction coupled with scRNA-seq and multi-omics approaches

Author

Lee, Muyoung, Guo, Qingqing, Kim, Mijeong, Choi, Joonhyuk, Segura, Alia, Genceroglu, Alper, LeBlanc, Lucy, Ramirez, Nereida, Jang, Yu Jin, Jang, Yeejin, Lee, Bum-Kyu, Marcotte, Edward M., and Kim, Jonghwan

Abstract

Transcriptional regulation controls cellular functions through interactions between transcription factors (TFs) and their chromosomal targets. However, understanding the fate conversion potential of multiple TFs in an inducible manner remains limited. Here, we introduce iTF-seq as a method for identifying individual TFs that can alter cell fate toward specific lineages at a single-cell level. iTF-seq enables time course monitoring of transcriptome changes, and with biotinylated individual TFs, it provides a multi-omics approach to understanding the mechanisms behind TF-mediated cell fate changes. Our iTF-seq study in mouse embryonic stem cells identified multiple TFs that trigger rapid transcriptome changes indicative of differentiation within a day of induction. Moreover, cells expressing these potent TFs often show a slower cell cycle and increased cell death. Further analysis using bioChIP-seq revealed that GCM1 and OTX2 act as pioneer factors and activators by increasing gene accessibility and activating the expression of lineage specification genes during cell fate conversion. iTF-seq has utility in both mapping cell fate conversion and understanding cell fate conversion mechanisms.

Published
2024
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9. 18nm FDSOI Enhanced Device Platform for ULP/ULL MCUs

Author

Weber, Olivier, primary, Min, Doohong, additional, Villaret, Alexandre, additional, Park, Jinha, additional, Lee, Ilmin, additional, Vandenbossche, Eric, additional, Kim, Dohun, additional, Yun, Jiyoung, additional, Park, Jinwoo, additional, Lee, Minuk, additional, Kang, Jinseok, additional, Lee, Hyunjong, additional, Choi, Youngju, additional, Kim, Inhwan, additional, Kim, Joochan, additional, Kedar, Dhori, additional, Janardan, Dhori Kedar, additional, Haendler, Sebastien, additional, Elghouli, Salim, additional, Puget, Sophie, additional, Bernicot, Christophe, additional, Bernard, Emilie, additional, Wacquant, Francois, additional, Nimsgern, Fabien, additional, Choi, Joonhyuk, additional, Maeda, Shigenobu, additional, Lee, Jongho, additional, and Arnaud, Franck, additional

Published
2022
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10. Synthetic recording and in situ readout of lineage information in single cells

Author

Frieda, Kirsten L., Linton, James M., Hormoz, Sahand, Choi, Joonhyuk, Chow, Ke-Huan K., Singer, Zakary S., Budde, Mark W., Elowitz, Michael B., and Cai, Long

Subjects
Cell interactions -- Observations, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Author(s): Kirsten L. Frieda [1]; James M. Linton [1]; Sahand Hormoz [1]; Joonhyuk Choi [2]; Ke-Huan K. Chow [1]; Zakary S. Singer [1]; Mark W. Budde [1]; Michael B. Elowitz [...]

Published
2017
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15. eSource records in clinical research: keeping it simple: how to satisfy regulatory concerns about EDC data integrity and site controls over its source records

Author

Mitchel, Jules T., Helfgott, Jonathan, Haag, Tom, Cappi, Silvana, Dunn, Imogene McCanless, Kim, Yong Joong, Choi, Joonhyuk, Cho, Timothy, and Gittleman, Dean

Subjects
United States. Food and Drug Administration -- Health policy, Regulatory compliance -- Methods, Clinical trials -- Methods -- Information management -- Laws, regulations and rules, General interest, Health
Abstract

There has been a recent thrust within the pharmaceutical industry to promote the transformation of the clinical trial process. In 2008, the Clinical Trial Transformational Initiative (CTTI), a public-private partnership [...]

Published
2015

16. Extremely delayed solitary cerebral metastasis in patient with T1N0M0 renal cell carcinoma after radical nephrectomy

Author

Choo, Yoon-Hee, Seo, Youngbeom, and Choi, Joonhyuk

Subjects
Male, renal cell carcinoma, Time Factors, delayed, Brain Neoplasms, brain, late, urologic and male genital diseases, Radiosurgery, Nephrectomy, female genital diseases and pregnancy complications, Kidney Neoplasms, Fatal Outcome, metastasis, Humans, Clinical Case Report, Postoperative Period, Carcinoma, Renal Cell, Craniotomy, Research Article, Aged
Abstract

Rationale: Although renal cell carcinoma (RCC) is one of the common origins of brain metastasis, few cases of extremely delayed brain metastasis from RCC, more than 10 years after nephrectomy, have been reported. We present a rare case of extremely delayed brain metastasis from RCC, also performed a literature review to increase knowledge of the characteristics for extremely delayed brain metastasis from RCC. Patient concerns: A 72-year-old man presented with right-sided hemiplegia and dysarthria. The patient had a history of radical nephrectomy for RCC with stage T1N0M0 15 years earlier. Diagnosis: Magnetic resonance imaging with contrast revealed a 2-cm sized non-homogenous enhanced mass in the left frontal lobe with peritumoral edema. The pathological examination after surgery reported metastatic clear cell RCC. Interventions: A craniotomy for removal of the mass was performed at the time of diagnosis. Stereotactic radiosurgery was performed for the tumor bed 3 weeks after craniotomy, and then, chemotherapy was started 2 months after the SRS. Outcomes: Metastasis progressed to multiple organs 6 months after the craniotomy. The patient chose a hospice and no longer visited the hospital. Lessons: In cases with a history of nephrectomy for RCC, long period follow-up is necessary for monitoring RCC brain metastasis and pathologic diagnosis should be confirmed.

Published
2021

20. Three-pronged approach to optimizing trial monitoring: study results using a quality-by-design method, risk-based monitoring, and real-time direct data entry

Author

Mitchel, Jules T., Cho, Timothy, Gittleman, Dean A., Markowitz, Judith M. Schloss, Kim, Yong Joong, Choi, Joonhyuk, Hamrell, Michael R., Nora, Sergio Dalla, and Carrara, Dario

Subjects
United States. Food and Drug Administration -- Standards, Sentinel health events -- Methods, Risk assessment -- Analysis, Clinical trials -- Usage, General interest, Health
Abstract

[PEER REVIEW] In order to support the transformation of how the pharmaceutical industry manages the performance of clinical trials, in 2013, the Food and Drug Administration (FDA) issued its final [...]

Published
2014

24. Mitochondrial volume fraction and translation duration impact mitochondrial mRNA localization and protein synthesis

Author

Tsuboi, Tatsuhisa, primary, Viana, Matheus P, additional, Xu, Fan, additional, Yu, Jingwen, additional, Chanchani, Raghav, additional, Arceo, Ximena G, additional, Tutucci, Evelina, additional, Choi, Joonhyuk, additional, Chen, Yang S, additional, Singer, Robert H, additional, Rafelski, Susanne M, additional, and Zid, Brian M, additional

Published
2020
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26. Author response: Mitochondrial volume fraction and translation duration impact mitochondrial mRNA localization and protein synthesis

Author

Tsuboi, Tatsuhisa, primary, Viana, Matheus P, additional, Xu, Fan, additional, Yu, Jingwen, additional, Chanchani, Raghav, additional, Arceo, Ximena G, additional, Tutucci, Evelina, additional, Choi, Joonhyuk, additional, Chen, Yang S, additional, Singer, Robert H, additional, Rafelski, Susanne M, additional, and Zid, Brian M, additional

Published
2020
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30. The final eFrontier: challenges and opportunities of integrating electronic data capture with electronic health records

Author

Mitchel, Jules T., Kim, Yong Joong, Choi, Joonhyuk, Park, Glen, Suciu, Laura, and Horn, Mark

Subjects
Medical records -- Usage -- Management, Clinical trials -- Information management, Data entry -- Methods -- Usage, Company business management, Company systems management, General interest, Health
Abstract

Historically, clinical trial data were collected at the clinical research site on pieces of paper designated as Source Documents. These data were transferred manually by the site to paper case [...]

Published
2010

31. Impact of IBCTs on clinical trial efficiency: this case study shows how Internet-based clinical trials improve data entry, monitoring, and management

Author

Mitchel, Jules T., Kim, Yong Joong, Choi, Joonhyuk, Hays, Vanessa, Langendorf, Jens, and Cappi, Silvana

Subjects
General interest, Health
Abstract

Barriers to entry for implementing an Internet-based clinical trial (IBCT; a.k.a, electronic data capture, or EDC) were described by Kelly and Oldham, (1) and very early on, it became clear [...]

Published
2006

33. The underutilization of EUS-guided biliary drainage: Perception of endoscopists in the East and West

Author

Park, DoHyun, primary, Yoon, WonJae, additional, Choi, JunHo, additional, Jang, Sunguk, additional, Samarasena, Jason, additional, Lee, TaeHoon, additional, Paik, WooHyun, additional, Oh, Dongwook, additional, Song, TaeJun, additional, Choi, JoonHyuk, additional, Hara, Kazuo, additional, Iwashita, Takuji, additional, Perez-Miranda, Manuel, additional, Lee, JohnG, additional, Vazquez-Sequeiros, Enrique, additional, Naitoh, Itaru, additional, Vila, JuanJ, additional, Brugge, WilliamR, additional, Takenaka, Mamoru, additional, Lee, SangSoo, additional, Seo, Dong-Wan, additional, Lee, SungKoo, additional, and Kim, Myung-Hwan, additional

Published
2019
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34. Inhibition of neural stem cell aging through the transient induction of reprogramming factors.

Author

Han, Min Ji, Lee, Won Ji, Choi, Joonhyuk, Hong, Yean Ju, Uhm, Sang Jun, Choi, Youngsok, and Do, Jeong Tae

Abstract

Adult stem cells age during long‐term in vitro culture, and neural stem cells (NSCs), which can self‐renew and differentiate into neurons and glial cells, also display reduced differentiation potential after repeated passaging. However, the mechanistic details underlying this process remain unclear. In this study, we found that long‐term in vitro culture of NSCs resulted in aging‐related upregulation of inflammatory‐ and endoplasmic reticulum (ER) stress‐related genes, including the proinflammatory cytokines interleukin (IL)1β and IL6, the senescence‐associated enzyme matrix metallopeptidase 13 (MMP13), and the ER stress‐responsive transcription factor activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP). However, the cyclic and transient induction of four reprogramming factors (POU domain, class 5, transcription factor 1, also known as octamer‐binding transcription factor 4; SRY [sex determining region Y]‐box 2; Kruppel‐like factor 4; and myelocytomatosis oncogene; collectively referred to as OSKM) can inhibit NSC aging, as indicated by the decreased expression of the inflammatory and ER stress‐related genes. We used ROSA‐4F NSCs, which express OSKM from only one allele, to minimize the potential for full reprogramming or tumor formation during NSC rejuvenation. We expect that this novel rejuvenation method will enhance the potential of NSCs as a clinical approach to the treatment of neurological diseases. [ABSTRACT FROM AUTHOR]

Published
2021
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35. Resistance switching characteristics in Li-doped NiO.

Author

Jung, Kyooho, Choi, Joonhyuk, Kim, Yongmin, Im, Hyunsik, Seo, Sunae, Jung, Ranju, Kim, DongChul, Kim, J.-S., Park, B. H., and Hong, J. P.

Subjects
*POLYCRYSTALLINE semiconductors, *THERMAL properties, *LITHIUM, *SEMICONDUCTOR doping, *SWITCHING in amorphous semiconductors
Abstract

We investigated the effects of lithium (Li)-doping on bi-stable resistance switching in polycrystalline NiO film in the temperature range of 10 K

Published
2008
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40. Sensing Inorganic Phosphate Starvation by the Phosphate-Responsive (PHO) Signaling Pathway of Saccharomyces cerevisiae

Author

Choi, Joonhyuk and O'Shea, Erin K

Subjects
Biochemistry, Chemistry, genetic screen, inorganic phosphate, metabolic profiling, metabolism
Abstract

Inorganic phosphate \((P_i)\) is an essential nutrient whose intracellular levels are maintained by the PHO pathway in Saccharomyces cerevisiae. \(P_i\) limitation triggers upregulation of the PHO genes whose gene products primarily function to counterbalance the \(P_i\) deficiency. Despite a growing catalogue of genes that are involved in signaling of the PHO pathway, little is known about how cells actually sense \(P_i\) limitation. To better characterize the \(P_i\) sensing mechanism, I exploited two comprehensive and orthogonal approaches: 1) genome-wide genetic screening to identify novel genes involved in signaling \(P_i\) limitation through the PHO pathway and characterization of genetic interactions among these genes and 2) liquid chromatography /mass spectrometry (LC/MS)-based metabolic profiling to characterize the metabolomic response to changes in \(P_i\) availability. In genome-wide screening, I found that the aah1 mutant constitutively activated the PHO pathway and showed that AAH1 is involved in regulating PHO pathway activity. Moreover, I identified several novel genetic interactions of genes involved in inositol polyphosphate metabolism with those involved in purine metabolism and mitochondrial fatty acid biosynthesis.Through metabolomic profiling, I showed that all adenine nucleotides were downregulated in the constitutively induced ado1, adk1, and aah1 mutants in high \(P_i\) as well as in the wild type strain in low \(P_i\). These observations led to the hypothesis that downregulation of adenine nucleotides triggers activation of the PHO pathway. However, I find that decreases in adenine nucleotides appear to be the consequence of downregulation of glycolysis and of the pentose phosphate pathway rather than an activation signal for the PHO pathway.Among all the detected metabolites, S-adenosyl-L-homocysteine (SAH) responded the most quickly and significantly to changes in \(P_i\) concentration. It was known that SAH is an inhibitor of de novo synthesis of phosphatidylcholine (PC). I showed that overall PC levels were downregulated in low \(P_i\), suggesting that phospholipid metabolism is downregulated in low \(P_i\) conditions. Furthermore, I observed that exogenous SAH induces activation of the PHO pathway in high \(P_i\) implying a possible role of SAH as an initiating activation signal of the PHO pathway., Chemistry and Chemical Biology

Published
2013

41. Analysis of microsatellite instability, protein expression and methylation status of hMLH1 and hMSH2 genes in gastric carcinomas.

Author

Gu M, Kim D, Bae Y, Choi J, Kim S, and Song S

Subjects
Adult, Aged, Aged, 80 and over, Carcinoma metabolism, Carcinoma pathology, Cohort Studies, Female, Humans, Male, Middle Aged, MutL Protein Homolog 1, Neoplasm Invasiveness, Retrospective Studies, Sensitivity and Specificity, Stomach Neoplasms metabolism, Stomach Neoplasms pathology, Adaptor Proteins, Signal Transducing physiology, Carcinoma genetics, Microsatellite Instability, MutS Homolog 2 Protein physiology, Nuclear Proteins physiology, Stomach Neoplasms genetics
Abstract

Background/aims: Microsatellite instability (MSI) is a manifestation of a defective DNA mismatch repair system. It is caused by germline mutations of mismatch repair genes or CpG islands hypermethylation. The majority of cancers of hereditary nonpolyposis colorectal cancer (HNPCC) syndrome have MSI+ phenotype. The colorectal cancers show distinctive clinicopathological characteristics and prognoses according to the MSI status. However, there is a wide variety of results between MSI and clinicopathological parameters in gastric carcinomas., Methodology: Five hundred and twenty-one surgically resected gastric carcinomas were studied and the correlation with clinicopathological parameters, MSI status by using five microsatellite markers, expression of hMLH1 and hMSH2 protein by immunohistochemical stain, and methylation of hMLH1 and hMSH2 by methylation-specific polymerase chain reaction was analyzed., Results: There were 50 (9.6%) high-frequency MSI (MSI-H) cases. The MSI-H gastric carcinomas were associated with older age, expanding type by Ming's classification, lymphatic invasion, tumor multiplicity, losses of hMLH1 and hMSH2 protein expressions. The methylation frequency of hMLH1 was 75.5% in MSI-H gastric carcinomas., Conclusions: Our results suggest that epigenetic inactivation of hMLH1 might play a role in the carcinogenesis of MSI-H gastric carcinomas. The immunohistochemical stain for hMLH1 protein expression could be used in routine diagnostic methods for predicting MSI status.

Published
2009

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