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1. Integrative Analysis of the Inflammatory Bowel Disease Serum Metabolome Improves Our Understanding of Genetic Etiology and Points to Novel Putative Therapeutic Targets

Author

Di'Narzo, Antonio F., Houten, Sander M., Kosoy, Roman, Huang, Ruiqi, Vaz, Frédéric M., Hou, Ruixue, Wei, Gabrielle, Wang, Wenhui, Comella, Phillip H., Dodatko, Tetyana, Rogatsky, Eduard, Stojmirovic, Aleksandar, Brodmerkel, Carrie, Perrigoue, Jacqueline, Hart, Amy, Curran, Mark, Friedman, Joshua R., Zhu, Jun, Agrawal, Manasi, Cho, Judy, Ungaro, Ryan, Dubinsky, Marla C., Sands, Bruce E., Suárez-Fariñas, Mayte, Schadt, Eric E., Colombel, Jean-Frédéric, Kasarskis, Andrew, Hao, Ke, and Argmann, Carmen

Published
2022
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2. Molecular Characterization of Limited Ulcerative Colitis Reveals Novel Biology and Predictors of Disease Extension

Author

Argmann, Carmen, Tokuyama, Minami, Ungaro, Ryan C., Huang, Ruiqi, Hou, Ruixue, Gurunathan, Sakteesh, Kosoy, Roman, Di’Narzo, Antonio, Wang, Wenhui, Losic, Bojan, Irizar, Haritz, Peters, Lauren, Stojmirovic, Aleksandar, Wei, Gabrielle, Comella, Phillip H., Curran, Mark, Brodmerkel, Carrie, Friedman, Joshua R., Hao, Ke, Schadt, Eric E., Zhu, Jun, Cho, Judy, Harpaz, Noam, Dubinsky, Marla C., Sands, Bruce E., Kasarskis, Andrew, Mehandru, Saurabh, Colombel, Jean-Frederic, and Suárez-Fariñas, Mayte

Published
2021
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3. Downregulation of exhausted cytotoxic T cells in gene expression networks of multisystem inflammatory syndrome in children

Author

Beckmann, Noam D., Comella, Phillip H., Cheng, Esther, Lepow, Lauren, Beckmann, Aviva G., Tyler, Scott R., Mouskas, Konstantinos, Simons, Nicole W., Hoffman, Gabriel E., Francoeur, Nancy J., Del Valle, Diane Marie, Kang, Gurpawan, Do, Anh, Moya, Emily, Wilkins, Lillian, Le Berichel, Jessica, Chang, Christie, Marvin, Robert, Calorossi, Sharlene, Lansky, Alona, Walker, Laura, Yi, Nancy, Yu, Alex, Chung, Jonathan, Hartnett, Matthew, Eaton, Melody, Hatem, Sandra, Jamal, Hajra, Akyatan, Alara, Tabachnikova, Alexandra, Liharska, Lora E., Cotter, Liam, Fennessy, Brian, Vaid, Akhil, Barturen, Guillermo, Shah, Hardik, Wang, Ying-chih, Sridhar, Shwetha Hara, Soto, Juan, Bose, Swaroop, Madrid, Kent, Ellis, Ethan, Merzier, Elyze, Vlachos, Konstantinos, Fishman, Nataly, Tin, Manying, Smith, Melissa, Xie, Hui, Patel, Manishkumar, Nie, Kai, Argueta, Kimberly, Harris, Jocelyn, Karekar, Neha, Batchelor, Craig, Lacunza, Jose, Yishak, Mahlet, Tuballes, Kevin, Scott, Ieisha, Kumar, Arvind, Jaladanki, Suraj, Agashe, Charuta, Thompson, Ryan, Clark, Evan, Losic, Bojan, Peters, Lauren, Roussos, Panagiotis, Zhu, Jun, Wang, Wenhui, Kasarskis, Andrew, Glicksberg, Benjamin S., Nadkarni, Girish, Bogunovic, Dusan, Elaiho, Cordelia, Gangadharan, Sandeep, Ofori-Amanfo, George, Alesso-Carra, Kasey, Onel, Kenan, Wilson, Karen M., Argmann, Carmen, Bunyavanich, Supinda, Alarcón-Riquelme, Marta E., Marron, Thomas U., Rahman, Adeeb, Kim-Schulze, Seunghee, Gnjatic, Sacha, Gelb, Bruce D., Merad, Miriam, Sebra, Robert, Schadt, Eric E., and Charney, Alexander W.

Published
2021
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4. Multiscale causal networks identify VGF as a key regulator of Alzheimer’s disease

Author

Beckmann, Noam D., Lin, Wei-Jye, Wang, Minghui, Cohain, Ariella T., Charney, Alexander W., Wang, Pei, Ma, Weiping, Wang, Ying-Chih, Jiang, Cheng, Audrain, Mickael, Comella, Phillip H., Fakira, Amanda K., Hariharan, Siddharth P., Belbin, Gillian M., Girdhar, Kiran, Levey, Allan I., Seyfried, Nicholas T., Dammer, Eric B., Duong, Duc, Lah, James J., Haure-Mirande, Jean-Vianney, Shackleton, Ben, Fanutza, Tomas, Blitzer, Robert, Kenny, Eimear, Zhu, Jun, Haroutunian, Vahram, Katsel, Pavel, Gandy, Sam, Tu, Zhidong, Ehrlich, Michelle E., Zhang, Bin, Salton, Stephen R., and Schadt, Eric E.

Published
2020
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6. Biopsy and blood-based molecular biomarker of inflammation in IBD.

Author

Argmann, Carmen, Ruixue Hou, Ungaro, Ryan C., Irizar, Haritz, Al-Taie, Zainab, Ruiqi Huang, Kosoy, Roman, Venkat, Swati, Song, Won-Min, Di’Narzo, Antonio F., Losic, Bojan, Ke Hao, Peters, Lauren, Comella, Phillip H., Wei, Gabrielle, Atreja, Ashish, Mahajan, Milind, Iuga, Alina, Desai, Prerak T., and Branigan, Patrick

Subjects
DISEASE remission, INTESTINAL diseases, INFLAMMATORY bowel diseases, INFLAMMATION, CROHN'S disease
Published
2023
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7. Biopsy and blood-based molecular biomarker of inflammation in IBD

Author

Argmann, Carmen, primary, Hou, Ruixue, additional, Ungaro, Ryan C, additional, Irizar, Haritz, additional, Al-Taie, Zainab, additional, Huang, Ruiqi, additional, Kosoy, Roman, additional, Venkat, Swati, additional, Song, Won-Min, additional, Di'Narzo, Antonio F, additional, Losic, Bojan, additional, Hao, Ke, additional, Peters, Lauren, additional, Comella, Phillip H, additional, Wei, Gabrielle, additional, Atreja, Ashish, additional, Mahajan, Milind, additional, Iuga, Alina, additional, Desai, Prerak T, additional, Branigan, Patrick, additional, Stojmirovic, Aleksandar, additional, Perrigoue, Jacqueline, additional, Brodmerkel, Carrie, additional, Curran, Mark, additional, Friedman, Joshua R, additional, Hart, Amy, additional, Lamousé-Smith, Esi, additional, Wehkamp, Jan, additional, Mehandru, Saurabh, additional, Schadt, Eric E, additional, Sands, Bruce E, additional, Dubinsky, Marla C, additional, Colombel, Jean-Frederic, additional, Kasarskis, Andrew, additional, and Suárez-Fariñas, Mayte, additional

Published
2022
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8. A Molecular network approach reveals shared cellular and molecular signatures between chronic fatigue syndrome and other fatiguing illnesses

Author

Comella, Phillip H., primary, Gonzalez-Kozlova, Edgar, additional, Kosoy, Roman, additional, Charney, Alexander W., additional, Peradejordi, Irene Font, additional, Chandrasekar, Shreya, additional, Tyler, Scott R., additional, Wang, Wenhui, additional, Losic, Bojan, additional, Zhu, Jun, additional, Hoffman, Gabriel E., additional, Kim-Schulze, Seunghee, additional, Qi, Jingjing, additional, Patel, Manishkumar, additional, Kasarskis, Andrew, additional, Suarez-Farinas, Mayte, additional, Gümüş, Zeynep H., additional, Argmann, Carmen, additional, Merad, Miriam, additional, Becker, Christian, additional, Beckmann, Noam D., additional, and Schadt, Eric E., additional

Published
2021
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9. Sampling the host response to SARS-CoV-2 in hospitals under siege

Author

Charney, Alexander W., Simons, Nicole W., Mouskas, Konstantinos, Lepow, Lauren, Cheng, Esther, Le Berichel, Jessica, Chang, Christie, Marvin, Robert, Del Valle, Diane Marie, Calorossi, Sharlene, Lansky, Alona, Walker, Laura, Patel, Manishkumar, Xie, Hui, Yi, Nancy, Yu, Alex, Kang, Gurpawan, Mendoza, Anthony, Liharska, Lora E., Moya, Emily, Hartnett, Matthew, Hatem, Sandra, Wilkins, Lillian, Eaton, Melody, Jamal, Hajra, Tuballes, Kevin, Chen, Steven T., Tabachnikova, Alexandra, Chung, Jonathan, Harris, Jocelyn, Batchelor, Craig, Lacunza, Jose, Yishak, Mahlet, Argueta, Kimberly, Karekar, Neha, Lee, Brian, Kelly, Geoffrey, Geanon, Daniel, Handler, Diana, Leech, John, Stefanos, Hiyab, Dawson, Travis, Scott, Ieisha, Francoeur, Nancy, Johnson, Jessica S., Vaid, Akhil, Glicksberg, Benjamin S., Nadkarni, Girish N., Schadt, Eric E., Gelb, Bruce D., Rahman, Adeeb, Sebra, Robert, Martin, Glenn, Agashe, Charuta, Agrawal, Priyal, Akyatan, Alara, Alesso-Carra, Kasey, Alibo, Eziwoma, Alvarez, Kelvin, Amabile, Angelo, Ascolillo, Steven, Bailey, Rasheed, Begani, Priya, Correra, Paloma Bravo, Brown, Stacey-Ann, Buckup, Mark, Burka, Larissa, Cambron, Lena, Carrara, Gina, Chang, Serena, Chien, Jonathan, Chowdhury, Mashkura, Bozkus, Cansu Cimen, Comella, Phillip, Cosgrove, Dana, Cossarini, Francesca, Cotter, Liam, Dave, Arpit, Dayal, Bheesham, Dhainaut, Maxime, Dornfeld, Rebecca, Dul, Katie, Eber, Nissan, Elaiho, Cordelia, Fabris, Frank, Faith, Jeremiah, Falci, Dominique, Feng, Susie, Fennessy, Brian, Fernandes, Marie, Gangadharan, Sandeep, Grabowska, Joanna, Gyimesi, Gavin, Hamdani, Maha, Herbinet, Manon, Herrera, Elva, Hochman, Arielle, Hoffman, Gabriel E., Hook, Jaime, Horta, Laila, Humblin, Etienne, Karim, Subha, Kim, Jessica, Lebovitch, Dannielle, Lee, Grace, Lee, Gyu Ho, Lee, Jacky, Leventhal, Mike, Lindblad, Katherine, Livanos, Alexandra, Machado, Rosalie, Mahmood, Zafar, Mar, Kelcey, Maskey, Shrisha, Matthews, Paul, Meckel, Katherine, Mehandru, Saurabh, Mercedes, Cynthia, Meyer, Dara, Mollaoglu, Gurkan, Morris, Sarah, Nie, Kai, Nisenholtz, Marjorie, Ofori-Amanfo, George, Onel, Kenan, Ounadjela, Merouane, Patel, Vishwendra, Pruitt, Cassandra, Rathi, Shivani, Redes, Jamie, Reyes-Torres, Ivan, Rodrigues, Alcina, Rodriguez, Alfonso, Roudko, Vladimir, Ruiz, Evelyn, Scalzo, Pearl, Silva, Pedro, Schanoski, Alessandra Soares, Straw, Meghan, Tabachnikova, Sasha, Teague, Collin, Upadhyaya, Bhaskar, Van Der Heide, Verena, Vaninov, Natalie, Wacker, Daniel, Walsh, Hadley, Wilk, C. Matthias, Wilson, Jessica, Wilson, Karen M., Xue, Li, Yeboah, Naa-akomaah, Young, Sabina, Zaks, Nina, Zha, Renyuan, Marron, Thomas, Beckmann, Noam, Kim-Schulze, Seunghee, Gnjatic, Sacha, and Merad, Miriam

Subjects
Siege, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), biology, business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Host response, Sampling (statistics), General Medicine, biology.organism_classification, Virology, General Biochemistry, Genetics and Molecular Biology, Pandemic, Medicine, business, Betacoronavirus
Published
2020
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10. Multiscale causal network models of Alzheimer’s disease identify VGF as a key regulator of disease

Author

Beckmann, Noam D., primary, Lin, Wei-Jye, additional, Wang, Minghui, additional, Cohain, Ariella T., additional, Wang, Pei, additional, Ma, Weiping, additional, Wang, Ying-Chih, additional, Jiang, Cheng, additional, Audrain, Mickael, additional, Comella, Phillip, additional, Hariharan, Siddharth P., additional, Belbin, Gillian M., additional, Levey, Allan I., additional, Seyfried, Nicholas T., additional, Dammer, Eric B., additional, Duong, Duc, additional, Lah, James J., additional, Haure-Mirande, Jean-Vianney, additional, Shackleton, Ben, additional, Charney, Alexander W., additional, Kenny, Eimear, additional, Zhu, Jun, additional, Haroutunian, Vahram, additional, Katsel, Pavel, additional, Gandy, Sam, additional, Tu, Zhidong, additional, Ehrlich, Michelle, additional, Zhang, Bin, additional, Salton, Stephen R., additional, and Schadt, Eric E., additional

Published
2018
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16. A Molecular network approach reveals shared cellular and molecular signatures between chronic fatigue syndrome and other fatiguing illnesses.

Author

Comella PH, Gonzalez-Kozlova E, Kosoy R, Charney AW, Peradejordi IF, Chandrasekar S, Tyler SR, Wang W, Losic B, Zhu J, Hoffman GE, Kim-Schulze S, Qi J, Patel M, Kasarskis A, Suarez-Farinas M, Gümüş ZH, Argmann C, Merad M, Becker C, Beckmann ND, and Schadt EE

Abstract

Competing Interests: Competing interest statement: The external patient data used to build the Bayesian network were partially funded as part of research alliance between Janssen Biotech and The Icahn School of Medicine at Mount Sinai.

Published
2021
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17. Cytotoxic lymphocytes are dysregulated in multisystem inflammatory syndrome in children.

Author

Beckmann ND, Comella PH, Cheng E, Lepow L, Beckmann AG, Mouskas K, Simons NW, Hoffman GE, Francoeur NJ, Del Valle DM, Kang G, Moya E, Wilkins L, Le Berichel J, Chang C, Marvin R, Calorossi S, Lansky A, Walker L, Yi N, Yu A, Hartnett M, Eaton M, Hatem S, Jamal H, Akyatan A, Tabachnikova A, Liharska LE, Cotter L, Fennessey B, Vaid A, Barturen G, Tyler SR, Shah H, Wang YC, Sridhar SH, Soto J, Bose S, Madrid K, Ellis E, Merzier E, Vlachos K, Fishman N, Tin M, Smith M, Xie H, Patel M, Argueta K, Harris J, Karekar N, Batchelor C, Lacunza J, Yishak M, Tuballes K, Scott L, Kumar A, Jaladanki S, Thompson R, Clark E, Losic B, Zhu J, Wang W, Kasarskis A, Glicksberg BS, Nadkarni G, Bogunovic D, Elaiho C, Gangadharan S, Ofori-Amanfo G, Alesso-Carra K, Onel K, Wilson KM, Argmann C, Alarcón-Riquelme ME, Marron TU, Rahman A, Kim-Schulze S, Gnjatic S, Gelb BD, Merad M, Sebra R, Schadt EE, and Charney AW

Abstract

Multisystem inflammatory syndrome in children (MIS-C) presents with fever, inflammation and multiple organ involvement in individuals under 21 years following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To identify genes, pathways and cell types driving MIS-C, we sequenced the blood transcriptomes of MIS-C cases, pediatric cases of coronavirus disease 2019, and healthy controls. We define a MIS-C transcriptional signature partially shared with the transcriptional response to SARS-CoV-2 infection and with the signature of Kawasaki disease, a clinically similar condition. By projecting the MIS-C signature onto a co-expression network, we identified disease gene modules and found genes downregulated in MIS-C clustered in a module enriched for the transcriptional signatures of exhausted CD8 + T-cells and CD56 dim CD57 + NK cells. Bayesian network analyses revealed nine key regulators of this module, including TBX21 , a central coordinator of exhausted CD8 + T-cell differentiation. Together, these findings suggest dysregulated cytotoxic lymphocyte response to SARS-Cov-2 infection in MIS-C.

Published
2020
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18. Hemagglutinin Stalk- and Neuraminidase-Specific Monoclonal Antibodies Protect against Lethal H10N8 Influenza Virus Infection in Mice.

Author

Wohlbold TJ, Chromikova V, Tan GS, Meade P, Amanat F, Comella P, Hirsh A, and Krammer F

Subjects
Animals, Antibodies, Monoclonal immunology, Antibodies, Neutralizing immunology, Antibodies, Viral immunology, Body Weight, Disease Models, Animal, Female, Hemagglutination Inhibition Tests, Hemagglutinin Glycoproteins, Influenza Virus immunology, Immunologic Factors immunology, Lung virology, Mice, Inbred BALB C, Neuraminidase immunology, Neutralization Tests, Orthomyxoviridae Infections immunology, Orthomyxoviridae Infections virology, Survival Analysis, Treatment Outcome, Viral Load, Viral Proteins immunology, Antibodies, Monoclonal administration & dosage, Antibodies, Neutralizing administration & dosage, Antibodies, Viral administration & dosage, Immunization, Passive methods, Immunologic Factors administration & dosage, Influenza A Virus, H10N8 Subtype immunology, Orthomyxoviridae Infections prevention & control
Abstract

Unlabelled: Between November 2013 and February 2014, China reported three human cases of H10N8 influenza virus infection in the Jiangxi province, two of which were fatal. Using hybridoma technology, we isolated a panel of H10- and N8-directed monoclonal antibodies (MAbs) and further characterized the binding reactivity of these antibodies (via enzyme-linked immunosorbent assay) to a range of purified virus and recombinant protein substrates. The H10-directed MAbs displayed functional hemagglutination inhibition (HI) and neutralization activity, and the N8-directed antibodies displayed functional neuraminidase inhibition (NI) activity against H10N8. Surprisingly, the HI-reactive H10 antibodies, as well as a previously generated, group 2 hemagglutinin (HA) stalk-reactive antibody, demonstrated NI activity against H10N8 and an H10N7 strain; this phenomenon was absent when virus was treated with detergent, suggesting the anti-HA antibodies inhibited neuraminidase enzymatic activity through steric hindrance. We tested the prophylactic efficacy of one representative H10-reactive, N8-reactive, and group 2 HA stalk-reactive antibody in vivo using a BALB/c challenge model. All three antibodies were protective at a high dose (5 mg/kg). At a low dose (0.5 mg/kg), only the anti-N8 antibody prevented weight loss. Together, these data suggest that antibody targets other than the globular head domain of the HA may be efficacious in preventing influenza virus-induced morbidity and mortality., Importance: Avian H10N8 and H10N7 viruses have recently crossed the species barrier, causing morbidity and mortality in humans and other mammals. Although these reports are likely isolated incidents, it is possible that more cases may emerge in future winter seasons, similar to H7N9. Furthermore, regular transmission of avian influenza viruses to humans increases the risk of adaptive mutations and reassortment events, which may result in a novel virus with pandemic potential. Currently, no specific therapeutics or vaccines are available against the H10N8 influenza virus subtype. We generated a panel of H10- and N8-reactive MAbs. Although these antibodies may practically be developed into therapeutic agents, characterizing the protective potential of MAbs that have targets other than the HA globular head domain will provide insight into novel antibody-mediated mechanisms of protection and help to better understand correlates of protection for influenza A virus infection., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Published
2015
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