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1,508 results on '"Coffey, Robert J."'

1. Temporal recording of mammalian development and precancer

Author

Islam, Mirazul, Yang, Yilin, Simmons, Alan J., Shah, Vishal M., Musale, Krushna Pavan, Xu, Yanwen, Tasneem, Naila, Chen, Zhengyi, Trinh, Linh T., Molina, Paola, Ramirez-Solano, Marisol A., Sadien, Iannish D., Dou, Jinzhuang, Rolong, Andrea, Chen, Ken, Magnuson, Mark A., Rathmell, Jeffrey C., Macara, Ian G., Winton, Douglas J., Liu, Qi, Zafar, Hamim, Kalhor, Reza, Church, George M., Shrubsole, Martha J., Coffey, Robert J., and Lau, Ken S.

Published
2024
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5. exRNA-eCLIP intersection analysis reveals a map of extracellular RNA binding proteins and associated RNAs across major human biofluids and carriers

Author

LaPlante, Emily L, Stürchler, Alessandra, Fullem, Robert, Chen, David, Starner, Anne C, Esquivel, Emmanuel, Alsop, Eric, Jackson, Andrew R, Ghiran, Ionita, Pereira, Getulio, Rozowsky, Joel, Chang, Justin, Gerstein, Mark B, Alexander, Roger P, Roth, Matthew E, Franklin, Jeffrey L, Coffey, Robert J, Raffai, Robert L, Mansuy, Isabelle M, Stavrakis, Stavros, deMello, Andrew J, Laurent, Louise C, Wang, Yi-Ting, Tsai, Chia-Feng, Liu, Tao, Jones, Jennifer, Van Keuren-Jensen, Kendall, Van Nostrand, Eric, Mateescu, Bogdan, and Milosavljevic, Aleksandar

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Genetics, Human Genome, Biotechnology, Underpinning research, 1.1 Normal biological development and functioning, Generic health relevance, NIH ERCC, RNA binding proteins, RNA footprint correlation, cell-free RNAs, cell-free biomarkers, eCLIP, exRNA carriers, human biofluids, liquid biopsies, public resource
Abstract

Although the role of RNA binding proteins (RBPs) in extracellular RNA (exRNA) biology is well established, their exRNA cargo and distribution across biofluids are largely unknown. To address this gap, we extend the exRNA Atlas resource by mapping exRNAs carried by extracellular RBPs (exRBPs). This map was developed through an integrative analysis of ENCODE enhanced crosslinking and immunoprecipitation (eCLIP) data (150 RBPs) and human exRNA profiles (6,930 samples). Computational analysis and experimental validation identified exRBPs in plasma, serum, saliva, urine, cerebrospinal fluid, and cell-culture-conditioned medium. exRBPs carry exRNA transcripts from small non-coding RNA biotypes, including microRNA (miRNA), piRNA, tRNA, small nuclear RNA (snRNA), small nucleolar RNA (snoRNA), Y RNA, and lncRNA, as well as protein-coding mRNA fragments. Computational deconvolution of exRBP RNA cargo reveals associations of exRBPs with extracellular vesicles, lipoproteins, and ribonucleoproteins across human biofluids. Overall, we mapped the distribution of exRBPs across human biofluids, presenting a resource for the community.

Published
2023

6. Phase 2 of extracellular RNA communication consortium charts next-generation approaches for extracellular RNA research

Author

Mateescu, Bogdan, Jones, Jennifer C, Alexander, Roger P, Alsop, Eric, An, Ji Yeong, Asghari, Mohammad, Boomgarden, Alex, Bouchareychas, Laura, Cayota, Alfonso, Chang, Hsueh-Chia, Charest, Al, Chiu, Daniel T, Coffey, Robert J, Das, Saumya, De Hoff, Peter, deMello, Andrew, D’Souza-Schorey, Crislyn, Elashoff, David, Eliato, Kiarash R, Franklin, Jeffrey L, Galas, David J, Gerstein, Mark B, Ghiran, Ionita H, Go, David B, Gould, Stephen, Grogan, Tristan R, Higginbotham, James N, Hladik, Florian, Huang, Tony Jun, Huo, Xiaoye, Hutchins, Elizabeth, Jeppesen, Dennis K, Jovanovic-Talisman, Tijana, Kim, Betty YS, Kim, Sung, Kim, Kyoung-Mee, Kim, Yong, Kitchen, Robert R, Knouse, Vaughan, LaPlante, Emily L, Lebrilla, Carlito B, Lee, L James, Lennon, Kathleen M, Li, Guoping, Li, Feng, Li, Tieyi, Liu, Tao, Liu, Zirui, Maddox, Adam L, McCarthy, Kyle, Meechoovet, Bessie, Maniya, Nalin, Meng, Yingchao, Milosavljevic, Aleksandar, Min, Byoung-Hoon, Morey, Amber, Ng, Martin, Nolan, John, De Oliveira, Getulio P, Paulaitis, Michael E, Phu, Tuan Anh, Raffai, Robert L, Reátegui, Eduardo, Roth, Matthew E, Routenberg, David A, Rozowsky, Joel, Rufo, Joseph, Senapati, Satyajyoti, Shachar, Sigal, Sharma, Himani, Sood, Anil K, Stavrakis, Stavros, Stürchler, Alessandra, Tewari, Muneesh, Tosar, Juan P, Tucker-Schwartz, Alexander K, Turchinovich, Andrey, Valkov, Nedyalka, Van Keuren-Jensen, Kendall, Vickers, Kasey C, Vojtech, Lucia, Vreeland, Wyatt N, Wang, Ceming, Wang, Kai, Wang, ZeYu, Welsh, Joshua A, Witwer, Kenneth W, Wong, David TW, Xia, Jianping, Xie, Ya-Hong, Yang, Kaichun, Zaborowski, Mikołaj P, Zhang, Chenguang, Zhang, Qin, Zivkovic, Angela M, and Laurent, Louise C

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Biochemistry, Biological sciences, Cell biology, Molecular biology
Abstract

The extracellular RNA communication consortium (ERCC) is an NIH-funded program aiming to promote the development of new technologies, resources, and knowledge about exRNAs and their carriers. After Phase 1 (2013-2018), Phase 2 of the program (ERCC2, 2019-2023) aims to fill critical gaps in knowledge and technology to enable rigorous and reproducible methods for separation and characterization of both bulk populations of exRNA carriers and single EVs. ERCC2 investigators are also developing new bioinformatic pipelines to promote data integration through the exRNA atlas database. ERCC2 has established several Working Groups (Resource Sharing, Reagent Development, Data Analysis and Coordination, Technology Development, nomenclature, and Scientific Outreach) to promote collaboration between ERCC2 members and the broader scientific community. We expect that ERCC2's current and future achievements will significantly improve our understanding of exRNA biology and the development of accurate and efficient exRNA-based diagnostic, prognostic, and theranostic biomarker assays.

Published
2022

8. Supermeres are functional extracellular nanoparticles replete with disease biomarkers and therapeutic targets

Author

Zhang, Qin, Jeppesen, Dennis K, Higginbotham, James N, Graves-Deal, Ramona, Trinh, Vincent Q, Ramirez, Marisol A, Sohn, Yoojin, Neininger, Abigail C, Taneja, Nilay, McKinley, Eliot T, Niitsu, Hiroaki, Cao, Zheng, Evans, Rachel, Glass, Sarah E, Ray, Kevin C, Fissell, William H, Hill, Salisha, Rose, Kristie Lindsey, Huh, Won Jae, Washington, Mary Kay, Ayers, Gregory Daniel, Burnette, Dylan T, Sharma, Shivani, Rome, Leonard H, Franklin, Jeffrey L, Lee, Youngmin A, Liu, Qi, and Coffey, Robert J

Subjects
Biochemistry and Cell Biology, Biological Sciences, Neurodegenerative, Bioengineering, Acquired Cognitive Impairment, Aging, Dementia, Neurosciences, Biotechnology, Rare Diseases, Brain Disorders, Orphan Drug, Nanotechnology, 2.1 Biological and endogenous factors, Cancer, Good Health and Well Being, Alzheimer Disease, Angiotensin-Converting Enzyme 2, Biological Transport, Biomarkers, COVID-19, Cardiovascular Diseases, Cell Communication, Cell Line, Tumor, Extracellular Vesicles, HeLa Cells, Humans, Lactic Acid, MicroRNAs, Nanoparticles, Neoplasms, Tumor Microenvironment, Hela Cells, Medical and Health Sciences, Developmental Biology, Biochemistry and cell biology
Abstract

Extracellular vesicles and exomere nanoparticles are under intense investigation as sources of clinically relevant cargo. Here we report the discovery of a distinct extracellular nanoparticle, termed supermere. Supermeres are morphologically distinct from exomeres and display a markedly greater uptake in vivo compared with small extracellular vesicles and exomeres. The protein and RNA composition of supermeres differs from small extracellular vesicles and exomeres. Supermeres are highly enriched with cargo involved in multiple cancers (glycolytic enzymes, TGFBI, miR-1246, MET, GPC1 and AGO2), Alzheimer's disease (APP) and cardiovascular disease (ACE2, ACE and PCSK9). The majority of extracellular RNA is associated with supermeres rather than small extracellular vesicles and exomeres. Cancer-derived supermeres increase lactate secretion, transfer cetuximab resistance and decrease hepatic lipids and glycogen in vivo. This study identifies a distinct functional nanoparticle replete with potential circulating biomarkers and therapeutic targets for a host of human diseases.

Published
2021

10. Molecular cartography uncovers evolutionary and microenvironmental dynamics in sporadic colorectal tumors

Author

Heiser, Cody N., Simmons, Alan J., Revetta, Frank, McKinley, Eliot T., Ramirez-Solano, Marisol A., Wang, Jiawei, Kaur, Harsimran, Shao, Justin, Ayers, Gregory D., Wang, Yu, Glass, Sarah E., Tasneem, Naila, Chen, Zhengyi, Qin, Yan, Kim, William, Rolong, Andrea, Chen, Bob, Vega, Paige N., Drewes, Julia L., Markham, Nicholas O., Saleh, Nabil, Nikolos, Fotis, Vandekar, Simon, Jones, Angela L., Washington, M. Kay, Roland, Joseph T., Chan, Keith S., Schürpf, Thomas, Sears, Cynthia L., Liu, Qi, Shrubsole, Martha J., Coffey, Robert J., and Lau, Ken S.

Published
2023
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12. The Human Tumor Atlas Network: Charting Tumor Transitions across Space and Time at Single-Cell Resolution.

Author

Rozenblatt-Rosen, Orit, Regev, Aviv, Oberdoerffer, Philipp, Nawy, Tal, Hupalowska, Anna, Rood, Jennifer E, Ashenberg, Orr, Cerami, Ethan, Coffey, Robert J, Demir, Emek, Ding, Li, Esplin, Edward D, Ford, James M, Goecks, Jeremy, Ghosh, Sharmistha, Gray, Joe W, Guinney, Justin, Hanlon, Sean E, Hughes, Shannon K, Hwang, E Shelley, Iacobuzio-Donahue, Christine A, Jané-Valbuena, Judit, Johnson, Bruce E, Lau, Ken S, Lively, Tracy, Mazzilli, Sarah A, Pe'er, Dana, Santagata, Sandro, Shalek, Alex K, Schapiro, Denis, Snyder, Michael P, Sorger, Peter K, Spira, Avrum E, Srivastava, Sudhir, Tan, Kai, West, Robert B, Williams, Elizabeth H, and Human Tumor Atlas Network

Subjects
Human Tumor Atlas Network, Humans, Neoplasms, Cell Transformation, Neoplastic, Genomics, Atlases as Topic, Single-Cell Analysis, Tumor Microenvironment, Precision Medicine, AI, Cancer Moonshot, Human Tumor Atlas, cancer transitions, data integration, data visualization, metastasis, pre-cancer, resistance, single-cell genomics, spatial genomics, spatial imaging, tumor, Human Genome, Clinical Research, Genetics, Cancer, Bioengineering, 2.1 Biological and endogenous factors, Aetiology, Good Health and Well Being, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

Crucial transitions in cancer-including tumor initiation, local expansion, metastasis, and therapeutic resistance-involve complex interactions between cells within the dynamic tumor ecosystem. Transformative single-cell genomics technologies and spatial multiplex in situ methods now provide an opportunity to interrogate this complexity at unprecedented resolution. The Human Tumor Atlas Network (HTAN), part of the National Cancer Institute (NCI) Cancer Moonshot Initiative, will establish a clinical, experimental, computational, and organizational framework to generate informative and accessible three-dimensional atlases of cancer transitions for a diverse set of tumor types. This effort complements both ongoing efforts to map healthy organs and previous large-scale cancer genomics approaches focused on bulk sequencing at a single point in time. Generating single-cell, multiparametric, longitudinal atlases and integrating them with clinical outcomes should help identify novel predictive biomarkers and features as well as therapeutically relevant cell types, cell states, and cellular interactions across transitions. The resulting tumor atlases should have a profound impact on our understanding of cancer biology and have the potential to improve cancer detection, prevention, and therapeutic discovery for better precision-medicine treatments of cancer patients and those at risk for cancer.

Published
2020

13. Heterogeneity within Stratified Epithelial Stem Cell Populations Maintains the Oral Mucosa in Response to Physiological Stress

Author

Byrd, Kevin M, Piehl, Natalie C, Patel, Jeet H, Huh, Won Jae, Sequeira, Inês, Lough, Kendall J, Wagner, Bethany L, Marangoni, Pauline, Watt, Fiona M, Klein, Ophir D, Coffey, Robert J, and Williams, Scott E

Subjects
Medical Biotechnology, Biomedical and Clinical Sciences, Stem Cell Research, Dental/Oral and Craniofacial Disease, Regenerative Medicine, Stem Cell Research - Nonembryonic - Non-Human, 1.1 Normal biological development and functioning, Animals, Cell Division, Cell Lineage, Cells, Cultured, Female, Flow Cytometry, Fluorescence, Immunohistochemistry, Male, Membrane Glycoproteins, Mice, Mouth Mucosa, Nerve Tissue Proteins, Stem Cells, Wound Healing, Igfbp5, Lrig1, label retention, lineage tracing, oral epithelium, oriented cell division, palate, soft diet, stem cell, wound healing, Biological Sciences, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

Stem cells in stratified epithelia are generally believed to adhere to a non-hierarchical single-progenitor model. Using lineage tracing and genetic label-retention assays, we show that the hard palatal epithelium of the oral cavity is unique in displaying marked proliferative heterogeneity. We identify a previously uncharacterized, infrequently-dividing stem cell population that resides within a candidate niche, the junctional zone (JZ). JZ stem cells tend to self-renew by planar symmetric divisions, respond to masticatory stresses, and promote wound healing, whereas frequently-dividing cells reside outside the JZ, preferentially renew through perpendicular asymmetric divisions, and are less responsive to injury. LRIG1 is enriched in the infrequently-dividing population in homeostasis, dynamically changes expression in response to tissue stresses, and promotes quiescence, whereas Igfbp5 preferentially labels a rapidly-growing, differentiation-prone population. These studies establish the oral mucosa as an important model system to study epithelial stem cell populations and how they respond to tissue stresses.

Published
2019

14. Reassessment of Exosome Composition

Author

Jeppesen, Dennis K, Fenix, Aidan M, Franklin, Jeffrey L, Higginbotham, James N, Zhang, Qin, Zimmerman, Lisa J, Liebler, Daniel C, Ping, Jie, Liu, Qi, Evans, Rachel, Fissell, William H, Patton, James G, Rome, Leonard H, Burnette, Dylan T, and Coffey, Robert J

Subjects
Biochemistry and Cell Biology, Biological Sciences, 1.1 Normal biological development and functioning, 2.1 Biological and endogenous factors, Annexin A1, Argonaute Proteins, Cell Line, Tumor, Cell Membrane, Cell-Derived Microparticles, DNA, Exosomes, Extracellular Vesicles, Female, Humans, Lysosomes, Male, Proteins, RNA, Argonaute, amphisomes, annexin, autophagy, exomeres, exosomes, extracellular DNA, extracellular RNA, extracellular vesicles, microvesicles, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

The heterogeneity of small extracellular vesicles and presence of non-vesicular extracellular matter have led to debate about contents and functional properties of exosomes. Here, we employ high-resolution density gradient fractionation and direct immunoaffinity capture to precisely characterize the RNA, DNA, and protein constituents of exosomes and other non-vesicle material. Extracellular RNA, RNA-binding proteins, and other cellular proteins are differentially expressed in exosomes and non-vesicle compartments. Argonaute 1-4, glycolytic enzymes, and cytoskeletal proteins were not detected in exosomes. We identify annexin A1 as a specific marker for microvesicles that are shed directly from the plasma membrane. We further show that small extracellular vesicles are not vehicles of active DNA release. Instead, we propose a new model for active secretion of extracellular DNA through an autophagy- and multivesicular-endosome-dependent but exosome-independent mechanism. This study demonstrates the need for a reassessment of exosome composition and offers a framework for a clearer understanding of extracellular vesicle heterogeneity.

Published
2019

15. The Extracellular RNA Communication Consortium: Establishing Foundational Knowledge and Technologies for Extracellular RNA Research

Author

Das, Saumya, Consortium, The Extracellular RNA Communication, Abdel-Mageed, Asim B, Adamidi, Catherine, Adelson, P David, Akat, Kemal M, Alsop, Eric, Ansel, K Mark, Arango, Jorge, Aronin, Neil, Avsaroglu, Seda Kilinc, Azizian, Azadeh, Balaj, Leonora, Ben-Dov, Iddo Z, Bertram, Karl, Bitzer, Markus, Blelloch, Robert, Bogardus, Kimberly A, Breakefield, Xandra Owens, Calin, George A, Carter, Bob S, Charest, Al, Chen, Clark C, Chitnis, Tanuja, Coffey, Robert J, Courtright-Lim, Amanda, Datta, Amrita, DeHoff, Peter, Diacovo, Thomas G, Erle, David J, Etheridge, Alton, Ferrer, Marc, Franklin, Jeffrey L, Freedman, Jane E, Galas, David J, Galeev, Timur, Gandhi, Roopali, Garcia, Aitor, Gerstein, Mark Bender, Ghai, Vikas, Ghiran, Ionita Calin, Giraldez, Maria D, Goga, Andrei, Gogakos, Tasos, Goilav, Beatrice, Gould, Stephen J, Guo, Peixuan, Gupta, Mihir, Hochberg, Fred, Huang, Bo, Huentelman, Matt, Hunter, Craig, Hutchins, Elizabeth, Jackson, Andrew R, Kalani, M Yashar S, Kanlikilicer, Pinar, Karaszti, Reka Agnes, Van Keuren-Jensen, Kendall, Khvorova, Anastasia, Kim, Yong, Kim, Hogyoung, Kim, Taek Kyun, Kitchen, Robert, Kraig, Richard P, Krichevsky, Anna M, Kwong, Raymond Y, Laurent, Louise C, Lee, Minyoung, L’Etoile, Noelle, Levy, Shawn E, Li, Feng, Li, Jenny, Li, Xin, Lopez-Berestein, Gabriel, Lucero, Rocco, Mateescu, Bogdan, Matin, AC, Max, Klaas EA, McManus, Michael T, Mempel, Thorsten R, Meyer, Cindy, Milosavljevic, Aleksandar, Mondal, Debasis, Mukamal, Kenneth Jay, Murillo, Oscar D, Muthukumar, Thangamani, Nickerson, Deborah A, O’Donnell, Christopher J, Patel, Dinshaw J, Patel, Tushar, Patton, James G, Paul, Anu, Peskind, Elaine R, Phelps, Mitch A, Putterman, Chaim, Quesenberry, Peter J, Quinn, Joseph F, Raffai, Robert L, and Ranabothu, Saritha

Subjects
Biological Sciences, Genetics, Biomarkers, Cell-Free Nucleic Acids, Extracellular Vesicles, Humans, Knowledge Bases, MicroRNAs, RNA, Extracellular RNA Communication Consortium, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

The Extracellular RNA Communication Consortium (ERCC) was launched to accelerate progress in the new field of extracellular RNA (exRNA) biology and to establish whether exRNAs and their carriers, including extracellular vesicles (EVs), can mediate intercellular communication and be utilized for clinical applications. Phase 1 of the ERCC focused on exRNA/EV biogenesis and function, discovery of exRNA biomarkers, development of exRNA/EV-based therapeutics, and construction of a robust set of reference exRNA profiles for a variety of biofluids. Here, we present progress by ERCC investigators in these areas, and we discuss collaborative projects directed at development of robust methods for EV/exRNA isolation and analysis and tools for sharing and computational analysis of exRNA profiling data.

Published
2019

17. Extracellular vesicles and nanoparticles at a glance.

Author

Jeppesen, Dennis K., Qin Zhang, and Coffey, Robert J.

Subjects
EXTRACELLULAR vesicles, EXTRACELLULAR space, NUCLEIC acids, EXOSOMES, NANOPARTICLES, BILAYER lipid membranes
Abstract

Cells can communicate with neighboring and more distant cells by secretion of extracellular vesicles (EVs). EVs are lipid bilayer membrane-bound structures that can be packaged with proteins, nucleic acids and lipids that mediate cell-cell signaling. EVs are increasingly recognized to play numerous important roles in both normal physiological processes and pathological conditions. Steady progress in the field has uncovered a great diversity and heterogeneity of distinct vesicle types that appear to be secreted from most, if not all, cell types. Recently, it has become apparent that cells also release non-vesicular extracellular nanoparticles (NVEPs), including the newly discovered exomeres and supermeres. In thisCell Science at a Glance article and the accompanying poster, we provide an overview of the diversity of EVs and nanoparticles that are released from cells into the extracellular space, highlighting recent advances in the field. [ABSTRACT FROM AUTHOR]

Published
2024
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18. MCMICRO: a scalable, modular image-processing pipeline for multiplexed tissue imaging

Author

Schapiro, Denis, Sokolov, Artem, Yapp, Clarence, Chen, Yu-An, Muhlich, Jeremy L., Hess, Joshua, Creason, Allison L., Nirmal, Ajit J., Baker, Gregory J., Nariya, Maulik K., Lin, Jia-Ren, Maliga, Zoltan, Jacobson, Connor A., Hodgman, Matthew W., Ruokonen, Juha, Farhi, Samouil L., Abbondanza, Domenic, McKinley, Eliot T., Persson, Daniel, Betts, Courtney, Sivagnanam, Shamilene, Regev, Aviv, Goecks, Jeremy, Coffey, Robert J., Coussens, Lisa M., Santagata, Sandro, and Sorger, Peter K.

Published
2022
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19. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

Author

Théry, Clotilde, Witwer, Kenneth W, Aikawa, Elena, Alcaraz, Maria Jose, Anderson, Johnathon D, Andriantsitohaina, Ramaroson, Antoniou, Anna, Arab, Tanina, Archer, Fabienne, Atkin‐Smith, Georgia K, Ayre, D Craig, Bach, Jean‐Marie, Bachurski, Daniel, Baharvand, Hossein, Balaj, Leonora, Baldacchino, Shawn, Bauer, Natalie N, Baxter, Amy A, Bebawy, Mary, Beckham, Carla, Zavec, Apolonija Bedina, Benmoussa, Abderrahim, Berardi, Anna C, Bergese, Paolo, Bielska, Ewa, Blenkiron, Cherie, Bobis‐Wozowicz, Sylwia, Boilard, Eric, Boireau, Wilfrid, Bongiovanni, Antonella, Borràs, Francesc E, Bosch, Steffi, Boulanger, Chantal M, Breakefield, Xandra, Breglio, Andrew M, Brennan, Meadhbh Á, Brigstock, David R, Brisson, Alain, Broekman, Marike LD, Bromberg, Jacqueline F, Bryl‐Górecka, Paulina, Buch, Shilpa, Buck, Amy H, Burger, Dylan, Busatto, Sara, Buschmann, Dominik, Bussolati, Benedetta, Buzás, Edit I, Byrd, James Bryan, Camussi, Giovanni, Carter, David RF, Caruso, Sarah, Chamley, Lawrence W, Chang, Yu‐Ting, Chen, Chihchen, Chen, Shuai, Cheng, Lesley, Chin, Andrew R, Clayton, Aled, Clerici, Stefano P, Cocks, Alex, Cocucci, Emanuele, Coffey, Robert J, Cordeiro‐da‐Silva, Anabela, Couch, Yvonne, Coumans, Frank AW, Coyle, Beth, Crescitelli, Rossella, Criado, Miria Ferreira, D'Souza‐Schorey, Crislyn, Das, Saumya, Chaudhuri, Amrita Datta, de Candia, Paola, De Santana, Eliezer F, De Wever, Olivier, del Portillo, Hernando A, Demaret, Tanguy, Deville, Sarah, Devitt, Andrew, Dhondt, Bert, Di Vizio, Dolores, Dieterich, Lothar C, Dolo, Vincenza, Rubio, Ana Paula Dominguez, Dominici, Massimo, Dourado, Mauricio R, Driedonks, Tom AP, Duarte, Filipe V, Duncan, Heather M, Eichenberger, Ramon M, Ekström, Karin, Andaloussi, Samir EL, Elie‐Caille, Celine, Erdbrügger, Uta, Falcón‐Pérez, Juan M, Fatima, Farah, Fish, Jason E, Flores‐Bellver, Miguel, Försönits, András, and Frelet‐Barrand, Annie

Subjects
Biochemistry and Cell Biology, Biological Sciences, extracellular vesicles, exosomes, ectosomes, microvesicles, minimal information requirements, guidelines, standardization, microparticles, rigor, reproducibility, Biochemistry and cell biology
Abstract

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles ("MISEV") guidelines for the field in 2014. We now update these "MISEV2014" guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.

Published
2018

20. Interaction of lncRNA MIR100HG with hnRNPA2B1 facilitates m6A-dependent stabilization of TCF7L2 mRNA and colorectal cancer progression

Author

Liu, Hao, Li, Danxiu, Sun, Lina, Qin, Hongqiang, Fan, Ahui, Meng, Lingnan, Graves-Deal, Ramona, Glass, Sarah E., Franklin, Jeffrey L., Liu, Qi, Wang, Jing, Yeatman, Timothy J., Guo, Hao, Zong, Hong, Jin, Shuilin, Chen, Zhiyu, Deng, Ting, Fang, Ying, Li, Cunxi, Karijolich, John, Patton, James G., Wang, Xin, Nie, Yongzhan, Fan, Daiming, Coffey, Robert J., Zhao, Xiaodi, and Lu, Yuanyuan

Published
2022
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23. Inhibition of EGFR/ErbB does not protect against C. difficile toxin B

Author

Siddiqi, Uswah, primary, Lunnemann, Hannah M., additional, Childress, Kevin O., additional, Shupe, John A., additional, Rutherford, Stacey A., additional, Farrow, Melissa A., additional, Washington, M. Kay, additional, Coffey, Robert J., additional, Lacy, D. Borden, additional, and Markham, Nicholas O., additional

Published
2024
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24. Differential pre-malignant programs and microenvironment chart distinct paths to malignancy in human colorectal polyps

Author

Chen, Bob, Scurrah, Cherie’ R., McKinley, Eliot T., Simmons, Alan J., Ramirez-Solano, Marisol A., Zhu, Xiangzhu, Markham, Nicholas O., Heiser, Cody N., Vega, Paige N., Rolong, Andrea, Kim, Hyeyon, Sheng, Quanhu, Drewes, Julia L., Zhou, Yuan, Southard-Smith, Austin N., Xu, Yanwen, Ro, James, Jones, Angela L., Revetta, Frank, Berry, Lynne D., Niitsu, Hiroaki, Islam, Mirazul, Pelka, Karin, Hofree, Matan, Chen, Jonathan H., Sarkizova, Siranush, Ng, Kimmie, Giannakis, Marios, Boland, Genevieve M., Aguirre, Andrew J., Anderson, Ana C., Rozenblatt-Rosen, Orit, Regev, Aviv, Hacohen, Nir, Kawasaki, Kenta, Sato, Toshiro, Goettel, Jeremy A., Grady, William M., Zheng, Wei, Washington, M. Kay, Cai, Qiuyin, Sears, Cynthia L., Goldenring, James R., Franklin, Jeffrey L., Su, Timothy, Huh, Won Jae, Vandekar, Simon, Roland, Joseph T., Liu, Qi, Coffey, Robert J., Shrubsole, Martha J., and Lau, Ken S.

Published
2021
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27. Extracellular RNA in oncogenesis, metastasis and drug resistance

Author

Nelson, Hannah, Qu, Sherman, Franklin, Jeffrey L., Liu, Qi, Pua, Heather H., Vickers, Kasey C., Weaver, Alissa M., Coffey, Robert J., and Patton, James G.

Abstract

ABSTRACTExtracellular vesicles and nanoparticles (EVPs) are now recognized as a novel form of cell–cell communication. All cells release a wide array of heterogeneous EVPs with distinct protein, lipid, and RNA content, dependent on the pathophysiological state of the donor cell. The overall cargo content in EVPs is not equivalent to cellular levels, implying a regulated pathway for selection and export. In cancer, release and uptake of EVPs within the tumour microenvironment can influence growth, proliferation, invasiveness, and immune evasion. Secreted EVPs can also have distant, systemic effects that can promote metastasis. Here, we review current knowledge of EVP biogenesis and cargo selection with a focus on the role that extracellular RNA plays in oncogenesis and metastasis. Almost all subtypes of RNA have been identified in EVPs, with miRNAs being the best characterized. We review the roles of specific miRNAs that have been detected in EVPs and that play a role in oncogenesis and metastasis.

Published
2024
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29. 5‐Fluorouracil treatment represses pseudouridine‐containing miRNA export into extracellular vesicles.

Author

Qu, Shimian, Nelson, Hannah M., Liu, Xiao, Wang, Yu, Semler, Elizabeth M., Michell, Danielle L., Massick, Clark, Franklin, Jeffrey L., Karijolich, John, Weaver, Alissa M., Coffey, Robert J., Liu, Qi, Vickers, Kasey C., and Patton, James G.

Subjects
GENE expression, RNA modification & restriction, RNA metabolism, NON-coding RNA, EXTRACELLULAR vesicles
Abstract

5‐Fluorouracil (5‐FU) has been used for chemotherapy for colorectal and other cancers for over 50 years. The prevailing view of its mechanism of action is inhibition of thymidine synthase leading to defects in DNA replication and repair. However, 5‐FU is also incorporated into RNA causing defects in RNA metabolism, inhibition of pseudouridine modification, and altered ribosome function. We examined the impact of 5‐FU on post‐transcriptional small RNA modifications (PTxMs) and the expression and export of RNA into small extracellular vesicles (sEVs). EVs are secreted by all cells and contain a variety of proteins and RNAs that can function in cell‐cell communication. We found that treatment of colorectal cancer (CRC) cells with 5‐FU represses sEV export of miRNA and snRNA‐derived RNAs, but promotes export of snoRNA‐derived RNAs. Strikingly, 5‐FU treatment significantly decreased the levels of pseudouridine on both cellular and sEV small RNA profiles. In contrast, 5‐FU exposure led to increased levels of cellular small RNAs containing a variety of methyl‐modified bases. These unexpected findings show that 5‐FU exposure leads to altered RNA expression, base modification, and aberrant trafficking and localization of small RNAs. [ABSTRACT FROM AUTHOR]

Published
2024
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30. Comparison of EV characterization by commercial high‐sensitivity flow cytometers and a custom single‐molecule flow cytometer.

Author

Kim, James, Xu, Shihan, Jung, Seung‐Ryoung, Nguyen, Alya, Cheng, Yuanhua, Zhao, Mengxia, Fujimoto, Bryant S., Nelson, Wyatt, Schiro, Perry, Franklin, Jeffrey L., Higginbotham, James N., Coffey, Robert J., Shi, Min, Vojtech, Lucia N., Hladik, Florian, Tewari, Muneesh, Tigges, John, Ghiran, Ionita, Jovanovic‐Talisman, Tijana, and Laurent, Louise C.

Subjects
EXTRACELLULAR vesicles, FLOW cytometry, DETECTION limit, COLORECTAL cancer, ELECTRIC vehicle industry
Abstract

High‐sensitivity flow cytometers have been developed for multi‐parameter characterization of single extracellular vesicles (EVs), but performance varies among instruments and calibration methods. Here we compare the characterization of identical (split) EV samples derived from human colorectal cancer (DiFi) cells by three high‐sensitivity flow cytometers, two commercial instruments, CytoFLEX/CellStream, and a custom single‐molecule flow cytometer (SMFC). DiFi EVs were stained with the membrane dye di‐8‐ANEPPS and with PE‐conjugated anti‐EGFR or anti‐tetraspanin (CD9/CD63/CD81) antibodies for estimation of EV size and surface protein copy numbers. The limits of detection (LODs) for immunofluorescence and vesicle size based on calibration using cross‐calibrated, hard‐dyed beads were ∼10 PE/∼80 nm EV diameter for CytoFLEX and ∼10 PEs/∼67 nm for CellStream. For the SMFC, the LOD for immunofluorescence was 1 PE and ≤ 35 nm for size. The population of EVs detected by each system (di‐8‐ANEPPS+/PE+ particles) differed widely depending on the LOD of the system; for example, CellStream/CytoFLEX detected only 5.7% and 1.5% of the tetraspanin‐labelled EVs detected by SMFC, respectively, and median EV diameter and antibody copy numbers were much larger for CellStream/CytoFLEX than for SMFC as measured and validated using super‐resolution/single‐molecule TIRF microscopy. To obtain a dataset representing a common EV population analysed by all three platforms, we filtered out SMFC and CellStream measurements for EVs below the CytoFLEX LODs as determined by bead calibration (10 PE/80 nm). The inter‐platform agreement using this filtered dataset was significantly better than for the unfiltered dataset, but even better concordance between results was obtained by applying higher cutoffs (21 PE/120 nm) determined by threshold analysis using the SMFC data. The results demonstrate the impact of specifying LODs to define the EV population analysed on inter‐instrument reproducibility in EV flow cytometry studies, and the utility of threshold analysis of SMFC data for providing semi‐quantitative LOD values for other flow cytometers. [ABSTRACT FROM AUTHOR]

Published
2024
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31. Succinate Produced by Intestinal Microbes Promotes Specification of Tuft Cells to Suppress Ileal Inflammation

Author

Banerjee, Amrita, Herring, Charles A., Chen, Bob, Kim, Hyeyon, Simmons, Alan J., Southard-Smith, Austin N., Allaman, Margaret M., White, James R., Macedonia, Mary C., Mckinley, Eliot T., Ramirez-Solano, Marisol A., Scoville, Elizabeth A., Liu, Qi, Wilson, Keith T., Coffey, Robert J., Washington, M. Kay, Goettel, Jeremy A., and Lau, Ken S.

Published
2020
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33. The Human Tumor Atlas Network: Charting Tumor Transitions across Space and Time at Single-Cell Resolution

Author

Aberle, Denise, Achilefu, Samuel I., Ademuyiwa, Foluso O., Adey, Andrew C., Aft, Rebecca L., Agarwal, Rachana, Aguilar, Ruben A., Alikarami, Fatemeh, Allaj, Viola, Amos, Christopher, Anders, Robert A., Angelo, Michael R., Anton, Kristen, Ashenberg, Orr, Aster, Jon C., Babur, Ozgun, Bahmani, Amir, Balsubramani, Akshay, Barrett, David, Beane, Jennifer, Bender, Diane E., Bernt, Kathrin, Berry, Lynne, Betts, Courtney B., Bletz, Julie, Blise, Katie, Boire, Adrienne, Boland, Genevieve, Borowsky, Alexander, Bosse, Kristopher, Bott, Matthew, Boyden, Ed, Brooks, James, Bueno, Raphael, Burlingame, Erik A., Cai, Qiuyin, Campbell, Joshua, Caravan, Wagma, Cerami, Ethan, Chaib, Hassan, Chan, Joseph M., Chang, Young Hwan, Chatterjee, Deyali, Chaudhary, Ojasvi, Chen, Alyce A., Chen, Bob, Chen, Changya, Chen, Chia-hui, Chen, Feng, Chen, Yu-An, Chheda, Milan G., Chin, Koei, Chiu, Roxanne, Chu, Shih-Kai, Chuaqui, Rodrigo, Chun, Jaeyoung, Cisneros, Luis, Coffey, Robert J., Colditz, Graham A., Cole, Kristina, Collins, Natalie, Contrepois, Kevin, Coussens, Lisa M., Creason, Allison L., Crichton, Daniel, Curtis, Christina, Davidsen, Tanja, Davies, Sherri R., de Bruijn, Ino, Dellostritto, Laura, De Marzo, Angelo, Demir, Emek, DeNardo, David G., Diep, Dinh, Ding, Li, Diskin, Sharon, Doan, Xengie, Drewes, Julia, Dubinett, Stephen, Dyer, Michael, Egger, Jacklynn, Eng, Jennifer, Engelhardt, Barbara, Erwin, Graham, Esplin, Edward D., Esserman, Laura, Felmeister, Alex, Feiler, Heidi S., Fields, Ryan C., Fisher, Stephen, Flaherty, Keith, Flournoy, Jennifer, Ford, James M., Fortunato, Angelo, Frangieh, Allison, Frye, Jennifer L., Fulton, Robert S., Galipeau, Danielle, Gan, Siting, Gao, Jianjiong, Gao, Long, Gao, Peng, Gao, Vianne R., Geiger, Tim, George, Ajit, Getz, Gad, Ghosh, Sharmistha, Giannakis, Marios, Gibbs, David L., Gillanders, William E., Goecks, Jeremy, Goedegebuure, Simon P., Gould, Alanna, Gowers, Kate, Gray, Joe W., Greenleaf, William, Gresham, Jeremy, Guerriero, Jennifer L., Guha, Tuhin K., Guimaraes, Alexander R., Guinney, Justin, Gutman, David, Hacohen, Nir, Hanlon, Sean, Hansen, Casey R., Harismendy, Olivier, Harris, Kathleen A., Hata, Aaron, Hayashi, Akimasa, Heiser, Cody, Helvie, Karla, Herndon, John M., Hirst, Gilliam, Hodi, Frank, Hollmann, Travis, Horning, Aaron, Hsieh, James J., Hughes, Shannon, Huh, Won Jae, Hunger, Stephen, Hwang, Shelley E., Iacobuzio-Donahue, Christine A., Ijaz, Heba, Izar, Benjamin, Jacobson, Connor A., Janes, Samuel, Jané-Valbuena, Judit, Jayasinghe, Reyka G., Jiang, Lihua, Johnson, Brett E., Johnson, Bruce, Ju, Tao, Kadara, Humam, Kaestner, Klaus, Kagan, Jacob, Kalinke, Lukas, Keith, Robert, Khan, Aziz, Kibbe, Warren, Kim, Albert H., Kim, Erika, Kim, Junhyong, Kolodzie, Annette, Kopytra, Mateusz, Kotler, Eran, Krueger, Robert, Krysan, Kostyantyn, Kundaje, Anshul, Ladabaum, Uri, Lake, Blue B., Lam, Huy, Laquindanum, Rozelle, Lau, Ken S., Laughney, Ashley M., Lee, Hayan, Lenburg, Marc, Leonard, Carina, Leshchiner, Ignaty, Levy, Rochelle, Li, Jerry, Lian, Christine G., Lim, Kian-Huat, Lin, Jia-Ren, Lin, Yiyun, Liu, Qi, Liu, Ruiyang, Lively, Tracy, Longabaugh, William J.R., Longacre, Teri, Ma, Cynthia X., Macedonia, Mary Catherine, Madison, Tyler, Maher, Christopher A., Maitra, Anirban, Makinen, Netta, Makowski, Danika, Maley, Carlo, Maliga, Zoltan, Mallo, Diego, Maris, John, Markham, Nick, Marks, Jeffrey, Martinez, Daniel, Mashl, Robert J., Masilionais, Ignas, Mason, Jennifer, Massagué, Joan, Massion, Pierre, Mattar, Marissa, Mazurchuk, Richard, Mazutis, Linas, Mazzilli, Sarah A., McKinley, Eliot T., McMichael, Joshua F., Merrick, Daniel, Meyerson, Matthew, Miessner, Julia R., Mills, Gordon B., Mills, Meredith, Mondal, Suman B., Mori, Motomi, Mori, Yuriko, Moses, Elizabeth, Mosse, Yael, Muhlich, Jeremy L., Murphy, George F., Navin, Nicholas E., Nawy, Tal, Nederlof, Michel, Ness, Reid, Nevins, Stephanie, Nikolov, Milen, Nirmal, Ajit Johnson, Nolan, Garry, Novikov, Edward, Oberdoerffer, Philipp, O’Connell, Brendan, Offin, Michael, Oh, Stephen T., Olson, Anastasiya, Ooms, Alex, Ossandon, Miguel, Owzar, Kouros, Parmar, Swapnil, Patel, Tasleema, Patti, Gary J., Pe’er, Dana, Pe'er, Itsik, Peng, Tao, Persson, Daniel, Petty, Marvin, Pfister, Hanspeter, Polyak, Kornelia, Pourfarhangi, Kamyar, Puram, Sidharth V., Qiu, Qi, Quintanal-Villalonga, Álvaro, Raj, Arjun, Ramirez-Solano, Marisol, Rashid, Rumana, Reeb, Ashley N., Regev, Aviv, Reid, Mary, Resnick, Adam, Reynolds, Sheila M., Riesterer, Jessica L., Rodig, Scott, Roland, Joseph T., Rosenfield, Sonia, Rotem, Asaf, Roy, Sudipta, Rozenblatt-Rosen, Orit, Rudin, Charles M., Ryser, Marc D., Santagata, Sandro, Santi-Vicini, Maria, Sato, Kazuhito, Schapiro, Denis, Schrag, Deborah, Schultz, Nikolaus, Sears, Cynthia L., Sears, Rosalie C., Sen, Subrata, Sen, Triparna, Shalek, Alex, Sheng, Jeff, Sheng, Quanhu, Shoghi, Kooresh I., Shrubsole, Martha J., Shyr, Yu, Sibley, Alexander B., Siex, Kiara, Simmons, Alan J., Singer, Dinah S., Sivagnanam, Shamilene, Slyper, Michal, Snyder, Michael P., Sokolov, Artem, Song, Sheng-Kwei, Sorger, Peter K., Southard-Smith, Austin, Spira, Avrum, Srivastava, Sudhir, Stein, Janet, Storm, Phillip, Stover, Elizabeth, Strand, Siri H., Su, Timothy, Sudar, Damir, Sullivan, Ryan, Surrey, Lea, Suvà, Mario, Tan, Kai, Terekhanova, Nadezhda V., Ternes, Luke, Thammavong, Lisa, Thibault, Guillaume, Thomas, George V., Thorsson, Vésteinn, Todres, Ellen, Tran, Linh, Tyler, Madison, Uzun, Yasin, Vachani, Anil, Van Allen, Eliezer, Vandekar, Simon, Veis, Deborah J., Vigneau, Sébastien, Vossough, Arastoo, Waanders, Angela, Wagle, Nikhil, Wang, Liang-Bo, Wendl, Michael C., West, Robert, Williams, Elizabeth H., Wu, Chi-yun, Wu, Hao, Wu, Hung-Yi, Wyczalkowski, Matthew A., Xie, Yubin, Yang, Xiaolu, Yapp, Clarence, Yu, Wenbao, Yuan, Yinyin, Zhang, Dadong, Zhang, Kun, Zhang, Mianlei, Zhang, Nancy, Zhang, Yantian, Zhao, Yanyan, Zhou, Daniel Cui, Zhou, Zilu, Zhu, Houxiang, Zhu, Qin, Zhu, Xiangzhu, Zhu, Yuankun, Zhuang, Xiaowei, Hupalowska, Anna, Rood, Jennifer E., Hanlon, Sean E., Hughes, Shannon K., Hwang, E. Shelley, Johnson, Bruce E., Shalek, Alex K., Spira, Avrum E., and West, Robert B.

Published
2020
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35. Scalable single-cell pooled CRISPR screens with conventional knockout vector libraries

Author

Islam, Mirazul, primary, Yang, Yilin, additional, Simmons, Alan J., additional, Xu, Yanwen, additional, Fisher, Emilie L., additional, Deng, Wentao, additional, Grieb, Brian C, additional, Molina, Paola, additional, de Caestecker, Christian, additional, Ramirez-Solano, Marisol A., additional, Liu, Qi, additional, Tansey, William P., additional, Macara, Ian G., additional, Rathmell, Jeffrey C., additional, Coffey, Robert J., additional, and Lau, Ken S., additional

Published
2024
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37. Transfer of Functional Cargo in Exomeres

Author

Zhang, Qin, Higginbotham, James N., Jeppesen, Dennis K., Yang, Yu-Ping, Li, Wei, McKinley, Eliot T., Graves-Deal, Ramona, Ping, Jie, Britain, Colleen M., Dorsett, Kaitlyn A., Hartman, Celine L., Ford, David A., Allen, Ryan M., Vickers, Kasey C., Liu, Qi, Franklin, Jeffrey L., Bellis, Susan L., and Coffey, Robert J.

Published
2019
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38. The Extracellular RNA Communication Consortium: Establishing Foundational Knowledge and Technologies for Extracellular RNA Research

Author

Abdel-Mageed, Asim B., Adamidi, Catherine, Adelson, P. David, Akat, Kemal M., Alsop, Eric, Ansel, K. Mark, Arango, Jorge, Aronin, Neil, Avsaroglu, Seda Kilinc, Azizian, Azadeh, Balaj, Leonora, Ben-Dov, Iddo Z., Bertram, Karl, Bitzer, Markus, Blelloch, Robert, Bogardus, Kimberly A., Breakefield, Xandra Owens, Calin, George A., Carter, Bob S., Charest, Al, Chen, Clark C., Chitnis, Tanuja, Coffey, Robert J., Courtright-Lim, Amanda, Das, Saumya, Datta, Amrita, DeHoff, Peter, Diacovo, Thomas G., Erle, David J., Etheridge, Alton, Ferrer, Marc, Franklin, Jeffrey L., Freedman, Jane E., Galas, David J., Galeev, Timur, Gandhi, Roopali, Garcia, Aitor, Gerstein, Mark Bender, Ghai, Vikas, Ghiran, Ionita Calin, Giraldez, Maria D., Goga, Andrei, Gogakos, Tasos, Goilav, Beatrice, Gould, Stephen J., Guo, Peixuan, Gupta, Mihir, Hochberg, Fred, Huang, Bo, Huentelman, Matt, Hunter, Craig, Hutchins, Elizabeth, Jackson, Andrew R., Kalani, M. Yashar S., Kanlikilicer, Pinar, Karaszti, Reka Agnes, Van Keuren-Jensen, Kendall, Khvorova, Anastasia, Kim, Yong, Kim, Hogyoung, Kim, Taek Kyun, Kitchen, Robert, Kraig, Richard P., Krichevsky, Anna M., Kwong, Raymond Y., Laurent, Louise C., Lee, Minyoung, L’Etoile, Noelle, Levy, Shawn E., Li, Feng, Li, Jenny, Li, Xin, Lopez-Berestein, Gabriel, Lucero, Rocco, Mateescu, Bogdan, Matin, A.C., Max, Klaas E.A., McManus, Michael T., Mempel, Thorsten R., Meyer, Cindy, Milosavljevic, Aleksandar, Mondal, Debasis, Mukamal, Kenneth Jay, Murillo, Oscar D., Muthukumar, Thangamani, Nickerson, Deborah A., O’Donnell, Christopher J., Patel, Dinshaw J., Patel, Tushar, Patton, James G., Paul, Anu, Peskind, Elaine R., Phelps, Mitch A., Putterman, Chaim, Quesenberry, Peter J., Quinn, Joseph F., Raffai, Robert L., Ranabothu, Saritha, Rao, Shannon Jiang, Rodriguez-Aguayo, Cristian, Rosenzweig, Anthony, Roth, Matthew E., Rozowsky, Joel, Sabatine, Marc S., Sakhanenko, Nikita A., Saugstad, Julie Anne, Schmittgen, Thomas D., Shah, Neethu, Shah, Ravi, Shedden, Kerby, Shi, Jian, Sood, Anil K., Sopeyin, Anuoluwapo, Spengler, Ryan M., Spetzler, Robert, Srinivasan, Srimeenakshi, Subramanian, Sai Lakshmi, Suthanthiran, Manikkam, Tanriverdi, Kahraman, Teng, Yun, Tewari, Muneesh, Thistlethwaite, William, Tuschl, Thomas, Urbanowicz, Karolina Kaczor, Vickers, Kasey C., Voinnet, Olivier, Wang, Kai, Weaver, Alissa M., Wei, Zhiyun, Weiner, Howard L., Weiss, Zachary R., Williams, Zev, Wong, David T.W., Woodruff, Prescott G., Xiao, Xinshu, Yan, Irene K., Yeri, Ashish, Zhang, Bing, Zhang, Huang-Ge, Breakefield, Xandra O., Charest, Alain, Gerstein, Mark B., and Saugstad, Julie A.

Published
2019
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39. Potential functional applications of extracellular vesicles: a report by the NIH Common Fund Extracellular RNA Communication Consortium.

Author

Quesenberry, Peter J, Aliotta, Jason, Camussi, Giovanni, Abdel-Mageed, Asim B, Wen, Sicheng, Goldberg, Laura, Zhang, Huang-Ge, Tetta, Ciro, Franklin, Jeffrey, Coffey, Robert J, Danielson, Kirsty, Subramanya, Vinita, Ghiran, Ionita, Das, Saumya, Chen, Clark C, Pusic, Kae M, Pusic, Aya D, Chatterjee, Devasis, Kraig, Richard P, Balaj, Leonora, and Dooner, Mark

Subjects
cancer, cell fate change, extracellular vesicles, functional effects, pulmonary heart disease, renal, Biochemistry and Cell Biology
Abstract

The NIH Extracellular RNA Communication Program's initiative on clinical utility of extracellular RNAs and therapeutic agents and developing scalable technologies is reviewed here. Background information and details of the projects are presented. The work has focused on modulation of target cell fate by extracellular vesicles (EVs) and RNA. Work on plant-derived vesicles is of intense interest, and non-mammalian sources of vesicles may represent a very promising source for different therapeutic approaches. Retro-viral-like particles are intriguing. Clearly, EVs share pathways with the assembly machinery of several other viruses, including human endogenous retrovirals (HERVs), and this convergence may explain the observation of viral-like particles containing viral proteins and nucleic acid in EVs. Dramatic effect on regeneration of damaged bone marrow, renal, pulmonary and cardiovascular tissue is demonstrated and discussed. These studies show restoration of injured cell function and the importance of heterogeneity of different vesicle populations. The potential for neural regeneration is explored, and the capacity to promote and reverse neoplasia by EV exposure is described. The tremendous clinical potential of EVs underlies many of these projects, and the importance of regulatory issues and the necessity of general manufacturing production (GMP) studies for eventual clinical trials are emphasized. Clinical trials are already being pursued and should expand dramatically in the near future.

Published
2015

40. miR-100 and miR-125bContribute to Enhanced Growth and Invasiveness

Author

Nelson, Hannah M., primary, Qu, Sherman, additional, Chapman, Sydney N., additional, Luthcke, Nicole L., additional, Schuster, Sara A., additional, Turnbull, Lauren A., additional, Shameer, Muhammad, additional, Guy, Lucas L., additional, Lu, Xiao, additional, Corn, Kevin C., additional, Vickers, Kasey C., additional, Liu, Qi, additional, Franklin, Jeffery L., additional, Weaver, Allissa M., additional, Rafat, Marjan, additional, Coffey, Robert J., additional, and Patton, James G., additional

Published
2024
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41. 5-Fluorouracil Treatment Represses Pseudouridine-Containing Small RNA Export into Extracellular Vesicles

Author

Qu, Sherman, primary, Nelson, Hannah, additional, Liu, Xiao, additional, Semler, Elizabeth, additional, Michell, Danielle L, additional, Massick, Clark, additional, Franklin, Jeffrey L, additional, Karijolich, John, additional, Weaver, Alissa M, additional, Coffey, Robert J, additional, Liu, Qi, additional, Vickers, Kasey, additional, and Patton, James G, additional

Published
2024
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42. Genetic variants of Adam17 differentially regulate TGFβ signaling to modify vascular pathology in mice and humans

Author

Kawasaki, Kyoko, Freimuth, Julia, Meyer, Dominique S, Lee, Marie M, Tochimoto-Okamoto, Akiko, Benzinou, Michael, Clermont, Frederic F, Wu, Gloria, Roy, Ritu, Letteboer, Tom GW, van Amstel, Johannes Kristian Ploos, Giraud, Sophie, Dupuis-Girod, Sophie, Lesca, Gaeten, Westermann, Cornelius JJ, Coffey, Robert J, and Akhurst, Rosemary J

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Rare Diseases, Stem Cell Research, Hematology, Pediatric, Stem Cell Research - Nonembryonic - Non-Human, Congenital Structural Anomalies, Aetiology, 2.1 Biological and endogenous factors, ADAM Proteins, ADAM17 Protein, Animals, Blood Vessels, Gene Expression Regulation, Genetic Variation, Humans, Immunohistochemistry, Luciferases, Mice, Mice, Inbred C57BL, NIH 3T3 Cells, Signal Transduction, Smad2 Protein, Transforming Growth Factor beta, Transforming Growth Factor beta1
Abstract

Outcome of TGFβ1 signaling is context dependent and differs between individuals due to germ-line genetic variation. To explore innate genetic variants that determine differential outcome of reduced TGFβ1 signaling, we dissected the modifier locus Tgfbm3, on mouse chromosome 12. On a NIH/OlaHsd genetic background, the Tgfbm3b(C57) haplotype suppresses prenatal lethality of Tgfb1(-/-) embryos and enhances nuclear accumulation of mothers against decapentaplegic homolog 2 (Smad2) in embryonic cells. Amino acid polymorphisms within a disintegrin and metalloprotease 17 (Adam17) can account, at least in part, for this Tgfbm3b effect. ADAM17 is known to down-regulate Smad2 signaling by shedding the extracellular domain of TGFβRI, and we show that the C57 variant is hypomorphic for down-regulation of Smad2/3-driven transcription. Genetic variation at Tgfbm3 or pharmacological inhibition of ADAM17, modulates postnatal circulating endothelial progenitor cell (CEPC) numbers via effects on TGFβRI activity. Because CEPC numbers correlate with angiogenic potential, this suggests that variant Adam17 is an innate modifier of adult angiogenesis, acting through TGFβR1. To determine whether human ADAM17 is also polymorphic and interacts with TGFβ signaling in human vascular disease, we investigated hereditary hemorrhagic telangiectasia (HHT), which is caused by mutations in TGFβ/bone morphogenetic protein receptor genes, ENG, encoding endoglin (HHT1), or ACVRL1 encoding ALK1 (HHT2), and considered a disease of excessive abnormal angiogenesis. HHT manifests highly variable incidence and severity of clinical features, ranging from small mucocutaneous telangiectases to life-threatening visceral and cerebral arteriovenous malformations (AVMs). We show that ADAM17 SNPs associate with the presence of pulmonary AVM in HHT1 but not HHT2, indicating genetic variation in ADAM17 can potentiate a TGFβ-regulated vascular disease.

Published
2014

45. Temporal recording of mammalian development and precancer

Author

Islam, Mirazul, primary, Yang, Yilin, additional, Simmons, Alan J., additional, Shah, Vishal M., additional, Pavan, Musale Krushna, additional, Xu, Yanwen, additional, Tasneem, Naila, additional, Chen, Zhengyi, additional, Trinh, Linh T., additional, Molina, Paola, additional, Ramirez-Solano, Marisol A., additional, Sadien, Iannish, additional, Dou, Jinzhuang, additional, Chen, Ken, additional, Magnuson, Mark A., additional, Rathmell, Jeffrey C., additional, Macara, Ian G., additional, Winton, Douglas, additional, Liu, Qi, additional, Zafar, Hamim, additional, Kalhor, Reza, additional, Church, George M., additional, Shrubsole, Martha J., additional, Coffey, Robert J., additional, and Lau, Ken S., additional

Published
2023
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50. A CGA/EGFR/GATA2 positive feedback circuit confers chemoresistance in gastric cancer

Author

Cao, Tianyu, Lu, Yuanyuan, Wang, Qi, Qin, Hongqiang, Li, Hongwei, Guo, Hao, Ge, Minghui, Glass, Sarah E., Singh, Bhuminder, Zhang, Wenyao, Dong, Jiaqiang, Du, Feng, Qian, Airong, Tian, Ye, Wang, Xin, Li, Cunxi, Wu, Kaichun, Fan, Daiming, Nie, Yongzhan, Coffey, Robert J., and Zhao, Xiaodi

Subjects
Oncology, Experimental, Drug resistance -- Research, Stomach cancer -- Genetic aspects -- Drug therapy, Chemotherapy -- Patient outcomes, Cellular signal transduction -- Research, Protein hormones -- Genetic aspects -- Health aspects, Cancer -- Chemotherapy -- Research, Transcription factors -- Health aspects, Health care industry
Abstract

De novo and acquired resistance are major impediments to the efficacy of conventional and targeted cancer therapy. In unselected gastric cancer (GC) patients with advanced disease, trials combining chemotherapy and an anti-EGFR monoclonal antibody have been largely unsuccessful. In an effort to identify biomarkers of resistance so as to better select patients for such trials, we screened the secretome of chemotherapy-treated human GC cell lines. We found that levels of CGA, the [alpha]-subunit of glycoprotein hormones, were markedly increased in the conditioned media of chemoresistant GC cells, and CGA immunoreactivity was enhanced in GC tissues that progressed on chemotherapy. CGA levels in plasma increased in GC patients who received chemotherapy, and this increase was correlated with reduced responsiveness to chemotherapy and poor survival. Mechanistically, secreted CGA was found to bind to EGFR and activate EGFR signaling, thereby conferring a survival advantage to GC cells. N-glycosylation of CGA at Asn52 and Asn78 is required for its stability, secretion, and interaction with EGFR. GATA2 was found to activate CGA transcription, whose increase, in turn, induced the expression and phosphorylation of GATA2 in an EGFR-dependent manner, forming a positive feedback circuit that was initiated by GATA2 autoregulation upon sublethal exposure to chemotherapy. Based on this circuit, combination strategies involving anti-EGFR therapies or targeting CGA with microRNAs (miR-708-3p and miR-761) restored chemotherapy sensitivity. These findings identify a clinically actionable CGA/EGFR/GATA2 circuit and highlight CGA as a predictive biomarker and therapeutic target in chemoresistant GC., Introduction Gastric cancer (GC) is the fifth most common malignancy worldwide but is the third leading cause of cancer-related deaths (1). The high mortality of GC is mainly attributed to [...]

Published
2022
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