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Comments on ‘An airway organoid-based screen identifies a role for the HIF1α‒glycolysis axis in SARS-CoV-2 infection’

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Journal of Molecular Cell Biology 2022年第1期14卷 60-61页

作者： Xiaohua Duan Hui Wang David D.Ho Robert E.Schwartz todd evans Shuibing Chen Department of Surgery Weill Cornell Medicine1300 York Ave.New YorkNY 10065USA State Key Laboratory of Oncogenes and Related Genes Center for Single-Cell OmicsSchool of Public HealthShanghai Jiao Tong University School of MedicineShanghai 200025China Aaron Diamond AIDS Research Center Columbia University Vagelos College of Physicians and SurgeonsNew YorkNY 10032USA Division of Gastroenterology and Hepatology Department of MedicineWeill Cornell Medicine1300 York Ave.New YorkNY 10065USA Department of Physiology Biophysics and Systems BiologyWeill Cornell Medicine1300 York Ave.New YorkNY 10065USA

Coronavirus disease 2019(COVID-19)has been an ongoing public health crisis since the end of 2019;besides vaccine development,there have been major research efforts focused on developing antiviral *** was the first US Food and Drug Administration(FDA)-approved antiviral drug for ***,the FDA granted emergency use authorization(EUA)for three monoclonal antibody treatments,including sotrovimab or a combination of casirivimab and imdevimab,or bamlanivimab and etesevimab,each of which targets the coronavirus spike protein to block viral *** recently,Britain granted conditional authorization for the ribonucleoside analog molnupiravir,developed by Merck as a viral replication *** protease inhibitor PF-07321332 developed by Pfizer and boosted by ritonavir showed promising results in a phase III clinical trial,reducing the risk of hospitalization or death by 89%compared with placebo.

关键词： Pfizer Merck vaccine

Chemical Biology for Identification of Novel Pathway Modulators and Generation of Specific Cardiac Cell Types

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Chemical Biology for Identification of Novel Pathway Modulat...

Dual role of lipids for genome stability and pluripotency facilitates full potency of mouse embryonic stem cells

第十届全国化学生物学学术会议

作者： todd evans Peter I Pressman Professor of Surgery Vice Chair of Surgery Associate Dean for Research Weill Cornell Medical College Cornell University

In the past decade, much progress has been made in the in vitro directed differentiation of tissue-specific progenitors and their derivatives from pluripotent stem cells, including embryonic stem cells. However, for most organ systems, including the heart, the efficiency is limited and derivatives are often heterogeneous, creating major challenges for generating functionally pure populations of certain cell types. This is important with regard to scalable generation of cells for eventual regenerative therapies and even in the short-term for modeling human disease "in a dish". We have pursued chemical biology approaches to enhance the efficiency of directed differentiation by coupling the use of reporter-based cell lines with chemical screens to enhance the generation of defined cellular phenotypes. For example, we developed a screen to identify modulators of the BMP signaling pathway, which is critical for efficient generation of cardiac progenitors. We have also designed screens to strategically enhance the specific differentiation of atrial or ventricular cardiomyocytes, and for generating otherwise rare cells of the cardiac conduction system. The screens have provided new tool reagents for generating defined cardiac cell populations to enhance disease modeling with human cells, including cells with defined genetic variation.

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Protein & Cell 2023年第8期14卷 591-602页

作者： Liangwen Zhong Miriam Gordillo Xingyi Wang Yiren Qin Yuanyuan Huang Alexey Soshnev Ritu Kumar Gouri Nanjangud Daylon James C.David Allis todd evans Bryce Carey Duancheng Wen Department of Reproductive Medicine Ronald O.Perelman and Claudia Cohen Center for Reproductive MedicineWeill Cornell MedicineNew YorkNY 10065USA Department of Surgery Weill Cornell Medical College1300 York AvenueNew YorkNY 10065USA Laboratory of Chromatin Biology and Epigenetics The Rockefeller UniversityNew YorkNY 10065USA Cold Spring Harbor Laboratory Cold Spring HarborNY 11724USA Molecular Cytogenetics Core.Memorial Sloan Kettering Cancer Center New YorkNY 10065USA Department of Neuroscience Developmental and Regenerative BiologyUniversity of Texas at San AntonioOne UTSA CircleSan AntonioTX 78249USA Gladstone Institutes 1650 Owens StSan FranciscoCA94158USA

While Mek1/2 and Gsk3βinhibition("2i")supports the maintenance of murine embryonic stem cells(EsCs)in a homogenous naive state,prolonged culture in 2i results in aneuploidy and DNA hypomethylation that impairs developmental ***,2i fails to support derivation and culture of fully potent female *** we find that mouse ESCs cultured in 2i/LIF supplemented with lipid-rich albumin(AlbuMAx)undergo pluripotency transition yet maintain genomic stability and full potency over long-term ***,lipids in AlbuMAx impact intracellular metabolism including nucleotide biosynthesis,lipid biogenesis,and TCA cycle intermediates,with enhanced expression of DNMT3s that prevent DNA *** induce a formative-like pluripotent state through direct stimulation of Erk2 phosphorylation,which also alleviates X chromosome loss in female ***,both male and female"all-ESc"mice can be generated from de novo derived ESCs using AlbuMAXbased *** findings underscore the importance of lipids to pluripotency and link nutrient cues to genome integrity in early development.

关键词： mouse pluripotent stem cells lipids pluripotency transition genomic stability developmental potency nucleotide pool depletion 2i medium X chromosome loss femaleall-EsC mice

A targetable pathway to eliminate TRA-1-60^(+)/TRA-1-81^(+)chemoresistant cancer cells

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Journal of Molecular Cell Biology 2023年第6期15卷 25-39页

作者： Lei Tan Xiaohua Duan Pratyusha Mutyala Ting Zhou Sadaf Amin Tuo Zhang Brian Herbst Gokce Askan Tomer Itkin Zhaoying Xiang Fabrizio Michelassi Michael D.Lieberman Christine AIacobuzio-Donahue Steven DLeach todd evans Shuibing Chen Department of Surgery Weill Cornell MedicineNew YorkNY 10065USA Center for Energy Metabolism and Reproduction Institute of Biomedicine and BiotechnologyShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China Center for Genomic Health Weill Cornell MedicineNew YorkNY 10065USA The SKI Stem Cell Research Facility The Center for Stem Cell Biology and Developmental Biology ProgramMemorial Sloan Kettering Cancer CenterNew YorkNY 10065USA Genomic Resource Core Facility Weill Cornell Medical CollegeNew YorkNY 10065USA Rubenstein Center for Pancreatic Cancer Research Memorial Sloan Kettering Cancer CenterNew YorkNY 10065USA Division of Regenerative Medicine Hartman Institute for Therapeutic Organ RegenerationAnsary Stem Cell InstituteDepartment of MedicineWeill Cornell MedicineNew YorkNY 10065USA Dartmouth Cancer Center Darmouth CollegeHanoverNH 03755USA

Chemoresistance is a primary cause of treatment failure in pancreatic *** cell surface markers specifically expressed in chemoresistant cancer cells(CCCs)could facilitate targeted therapies to overcome *** performed an antibody-based screen and found that TRA-1-60 and TRA-1-81,two‘stemness’cell surface markers,are highly enriched in ***-more,TRA-1-60^(+)/TRA-1-81^(+)cells are chemoresistant compared to TRA-1-60^(-)/TRA-1-81^(-)*** profiling identified UGT1A10,shown to be both necessary and sufficient to maintain TRA-1-60/TRA-1-81 expression and *** a high-content chemical screen,we identified Cymarin,which downregulates UGT1A10,eliminates TRA-1-60/TRA-1-81 expression,and increases chemosensitivity both in vitro and in ***,TRA-1-60/TRA-1-81 expression is highly specific in primary cancer tissue and positively correlated with chemoresistance and short survival,which highlights their potentiality for targeted ***,we discovered a novel CCC surface marker regulated by a pathway that promotes chemoresistance,as well as a leading drug candidate to target this pathway.

关键词： pancreatic cancer TRA-1-60/TRA-1-81 chemoresistance UGT1A10 Cymarin

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水平井流入动态计算

吐哈油气 1999年第2期4卷 59-67页

作者： L.K.Thomas B.j.todd C.E.evans R.G.Pierson 伍建林马玉信

本文提出了在超平衡或欠平衡条件下完钻的、用裸眼完井、割缝衬管完井或套管射孔完井的水平井的近井带表皮因子和非达西流动系数的计算方法,给出了以前出版的有关水平井的表皮因子和非达西流动系数方程并进行了比较。此外,还提出了水平... 详细信息

本文提出了在超平衡或欠平衡条件下完钻的、用裸眼完井、割缝衬管完井或套管射孔完井的水平井的近井带表皮因子和非达西流动系数的计算方法,给出了以前出版的有关水平井的表皮因子和非达西流动系数方程并进行了比较。此外,还提出了水平井的表皮因子和非达西流动系数的分析解和数值解,并对它们进行了比较。

关键词：水平井流入动态表皮因子计算