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Seok Junhee Seok

Bio: Seok Junhee Seok is an academic researcher from Stanford University. The author has an hindex of 1, co-authored 1 publications receiving 2189 citations.

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TL;DR: This study shows that, although acute inflammatory stresses from different etiologies result in highly similar genomic responses in humans, the responses in corresponding mouse models correlate poorly with the human conditions and also, one another.
Abstract: A cornerstone of modern biomedical research is the use of mouse models to explore basic pathophysiological mechanisms, evaluate new therapeutic approaches, and make go or no-go decisions to carry new drug candidates forward into clinical trials. Systematic studies evaluating how well murine models mimic human inflammatory diseases are nonexistent. Here, we show that, although acute inflammatory stresses from different etiologies result in highly similar genomic responses in humans, the responses in corresponding mouse models correlate poorly with the human conditions and also, one another. Among genes changed significantly in humans, the murine orthologs are close to random in matching their human counterparts (e.g., R2 between 0.0 and 0.1). In addition to improvements in the current animal model systems, our study supports higher priority for translational medical research to focus on the more complex human conditions rather than relying on mouse models to study human inflammatory diseases.

2,438 citations


Cited by
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TL;DR: A review of the basis, diagnosis, and current treatment of Sepsis in patients with this disorder is examined.
Abstract: Morbidity and mortality from sepsis remains unacceptably high. Large variability in clinical practice, plus the increasing awareness that certain processes of care associated with improved critical...

2,927 citations

Journal ArticleDOI
TL;DR: Biomarker-guided immunotherapy that is administered to patients at the proper immune phase of sepsis is potentially a major advance in the treatment of septicaemia and in the field of infectious disease.
Abstract: Sepsis - which is a severe life-threatening infection with organ dysfunction - initiates a complex interplay of host pro-inflammatory and anti-inflammatory processes. Sepsis can be considered a race to the death between the pathogens and the host immune system, and it is the proper balance between the often competing pro- and anti-inflammatory pathways that determines the fate of the individual. Although the field of sepsis research has witnessed the failure of many highly touted clinical trials, a better understanding of the pathophysiological basis of the disorder and the mechanisms responsible for the associated pro- and anti-inflammatory responses provides a novel approach for treating this highly lethal condition. Biomarker-guided immunotherapy that is administered to patients at the proper immune phase of sepsis is potentially a major advance in the treatment of sepsis and in the field of infectious disease.

1,719 citations

Journal ArticleDOI
Feng Yue1, Feng Yue2, Yong Cheng3, Alessandra Breschi, Jeff Vierstra4, Weisheng Wu2, Weisheng Wu5, Tyrone Ryba6, Tyrone Ryba7, Richard Sandstrom4, Zhihai Ma3, Carrie A. Davis8, Benjamin D. Pope6, Yin Shen1, Dmitri D. Pervouchine, Sarah Djebali, Robert E. Thurman4, Rajinder Kaul4, Eric Rynes4, Anthony Kirilusha9, Georgi K. Marinov9, Brian A. Williams9, Diane Trout9, Henry Amrhein9, Katherine I. Fisher-Aylor9, Igor Antoshechkin9, Gilberto DeSalvo9, Lei Hoon See8, Meagan Fastuca8, Jorg Drenkow8, Chris Zaleski8, Alexander Dobin8, Pablo Prieto, Julien Lagarde, Giovanni Bussotti, Andrea Tanzer10, Olgert Denas11, Kanwei Li11, M. A. Bender12, M. A. Bender4, Miaohua Zhang12, Rachel Byron12, Mark Groudine4, Mark Groudine12, David McCleary1, Long Pham1, Zhen Ye1, Samantha Kuan1, Lee Edsall1, Yi-Chieh Wu13, Matthew D. Rasmussen13, Mukul S. Bansal13, Manolis Kellis14, Manolis Kellis13, Cheryl A. Keller2, Christapher S. Morrissey2, Tejaswini Mishra2, Deepti Jain2, Nergiz Dogan2, Robert S. Harris2, Philip Cayting3, Trupti Kawli3, Alan P. Boyle5, Alan P. Boyle3, Ghia Euskirchen3, Anshul Kundaje3, Shin Lin3, Yiing Lin3, Camden Jansen15, Venkat S. Malladi3, Melissa S. Cline16, Drew T. Erickson3, Vanessa M. Kirkup16, Katrina Learned16, Cricket A. Sloan3, Kate R. Rosenbloom16, Beatriz Lacerda de Sousa17, Kathryn Beal, Miguel Pignatelli, Paul Flicek, Jin Lian18, Tamer Kahveci19, Dongwon Lee20, W. James Kent16, Miguel Santos17, Javier Herrero21, Cedric Notredame, Audra K. Johnson4, Shinny Vong4, Kristen Lee4, Daniel Bates4, Fidencio Neri4, Morgan Diegel4, Theresa K. Canfield4, Peter J. Sabo4, Matthew S. Wilken4, Thomas A. Reh4, Erika Giste4, Anthony Shafer4, Tanya Kutyavin4, Eric Haugen4, Douglas Dunn4, Alex Reynolds4, Shane Neph4, Richard Humbert4, R. Scott Hansen4, Marella F. T. R. de Bruijn22, Licia Selleri23, Alexander Y. Rudensky24, Steven Z. Josefowicz24, Robert M. Samstein24, Evan E. Eichler4, Stuart H. Orkin25, Dana N. Levasseur26, Thalia Papayannopoulou4, Kai Hsin Chang4, Arthur I. Skoultchi27, Srikanta Gosh27, Christine M. Disteche4, Piper M. Treuting4, Yanli Wang2, Mitchell J. Weiss, Gerd A. Blobel28, Xiaoyi Cao1, Sheng Zhong1, Ting Wang29, Peter J. Good30, Rebecca F. Lowdon30, Rebecca F. Lowdon29, Leslie B. Adams30, Leslie B. Adams31, Xiao Qiao Zhou30, Michael J. Pazin30, Elise A. Feingold30, Barbara J. Wold9, James Taylor11, Ali Mortazavi15, Sherman M. Weissman18, John A. Stamatoyannopoulos4, Michael Snyder3, Roderic Guigó, Thomas R. Gingeras8, David M. Gilbert6, Ross C. Hardison2, Michael A. Beer20, Bing Ren1 
20 Nov 2014-Nature
TL;DR: The mouse ENCODE Consortium has mapped transcription, DNase I hypersensitivity, transcription factor binding, chromatin modifications and replication domains throughout the mouse genome in diverse cell and tissue types as mentioned in this paper.
Abstract: The laboratory mouse shares the majority of its protein-coding genes with humans, making it the premier model organism in biomedical research, yet the two mammals differ in significant ways To gain greater insights into both shared and species-specific transcriptional and cellular regulatory programs in the mouse, the Mouse ENCODE Consortium has mapped transcription, DNase I hypersensitivity, transcription factor binding, chromatin modifications and replication domains throughout the mouse genome in diverse cell and tissue types By comparing with the human genome, we not only confirm substantial conservation in the newly annotated potential functional sequences, but also find a large degree of divergence of sequences involved in transcriptional regulation, chromatin state and higher order chromatin organization Our results illuminate the wide range of evolutionary forces acting on genes and their regulatory regions, and provide a general resource for research into mammalian biology and mechanisms of human diseases

1,335 citations

20 Nov 2014
TL;DR: The laboratory mouse shares the majority of its protein-coding genes with humans, making it the premier model organism in biomedical research, yet the two mammals differ in significant ways.
Abstract: © 2014 Macmillan Publishers Limited. All rights reserved.The laboratory mouse shares the majority of its protein-coding genes with humans, making it the premier model organism in biomedical research, yet the two mammals differ in significant ways. To gain

1,020 citations

Journal ArticleDOI
TL;DR: A comprehensive longitudinal review of AstraZeneca's small-molecule drug projects from 2005 to 2010 allowed us to establish a framework based on the five most important technical determinants of project success and pipeline quality, which are described as the five 'R's'.
Abstract: Maintaining research and development (R&D) productivity at a sustainable level is one of the main challenges currently facing the pharmaceutical industry. In this article, we discuss the results of a comprehensive longitudinal review of AstraZeneca's small-molecule drug projects from 2005 to 2010. The analysis allowed us to establish a framework based on the five most important technical determinants of project success and pipeline quality, which we describe as the five 'R's: the right target, the right patient, the right tissue, the right safety and the right commercial potential. A sixth factor - the right culture - is also crucial in encouraging effective decision-making based on these technical determinants. AstraZeneca is currently applying this framework to guide its R&D teams, and although it is too early to demonstrate whether this has improved the company's R&D productivity, we present our data and analysis here in the hope that it may assist the industry overall in addressing this key challenge.

1,003 citations