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36 results on '"Greenbaum, Benjamin D."'

1. Structures, functions and adaptations of the human LINE-1 ORF2 protein

Author

Baldwin, Eric T., van Eeuwen, Trevor, Hoyos, David, Zalevsky, Arthur, Tchesnokov, Egor P., Sánchez, Roberto, Miller, Bryant D., Di Stefano, Luciano H., Ruiz, Francesc Xavier, Hancock, Matthew, Işik, Esin, Mendez-Dorantes, Carlos, Walpole, Thomas, Nichols, Charles, Wan, Paul, Riento, Kirsi, Halls-Kass, Rowan, Augustin, Martin, Lammens, Alfred, Jestel, Anja, Upla, Paula, Xibinaku, Kera, Congreve, Samantha, Hennink, Maximiliaan, Rogala, Kacper B., Schneider, Anna M., Fairman, Jennifer E., Christensen, Shawn M., Desrosiers, Brian, Bisacchi, Gregory S., Saunders, Oliver L., Hafeez, Nafeeza, Miao, Wenyan, Kapeller, Rosana, Zaller, Dennis M., Sali, Andrej, Weichenrieder, Oliver, Burns, Kathleen H., Götte, Matthias, Rout, Michael P., Arnold, Eddy, Greenbaum, Benjamin D., Romero, Donna L., LaCava, John, and Taylor, Martin S.

Published
2024
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2. How different are self and nonself?

Author

Mayer, Andreas, Russo, Christopher J., Marcou, Quentin, Bialek, William, and Greenbaum, Benjamin D.

Subjects
Quantitative Biology - Cell Behavior
Abstract

Biological and artificial neural networks routinely make reliable distinctions between similar inputs, and the rules for making these distinctions are learned. In some ways, self/nonself discrimination in the immune system is similar, being both reliable and (partly) learned through thymic selection. In contrast to other examples, we show that the distributions of self and nonself peptides are nearly identical but strongly inhomogeneous. Reliable discrimination is possible only because self peptides are a particular finite sample drawn out of this distribution, and the immune system can target the ``spaces'' in between these samples. In conventional learning problems, this would constitute overfitting and lead to disaster. Here, the strong inhomogeneities imply instead that the immune system gains by targeting peptides which are very similar to self, with maximum sensitivity for sequences just one substitution away. This prediction from the structure of the underlying distribution in sequence space agrees, for example, with the observed responses to cancer neoantigens.

Published
2022

4. Personalized RNA neoantigen vaccines stimulate T cells in pancreatic cancer

Author

Rojas, Luis A., Sethna, Zachary, Soares, Kevin C., Olcese, Cristina, Pang, Nan, Patterson, Erin, Lihm, Jayon, Ceglia, Nicholas, Guasp, Pablo, Chu, Alexander, Yu, Rebecca, Chandra, Adrienne Kaya, Waters, Theresa, Ruan, Jennifer, Amisaki, Masataka, Zebboudj, Abderezak, Odgerel, Zagaa, Payne, George, Derhovanessian, Evelyna, Müller, Felicitas, Rhee, Ina, Yadav, Mahesh, Dobrin, Anton, Sadelain, Michel, Łuksza, Marta, Cohen, Noah, Tang, Laura, Basturk, Olca, Gönen, Mithat, Katz, Seth, Do, Richard Kinh, Epstein, Andrew S., Momtaz, Parisa, Park, Wungki, Sugarman, Ryan, Varghese, Anna M., Won, Elizabeth, Desai, Avni, Wei, Alice C., D’Angelica, Michael I., Kingham, T. Peter, Mellman, Ira, Merghoub, Taha, Wolchok, Jedd D., Sahin, Ugur, Türeci, Özlem, Greenbaum, Benjamin D., Jarnagin, William R., Drebin, Jeffrey, O’Reilly, Eileen M., and Balachandran, Vinod P.

Published
2023
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5. Genomic and transcriptomic analysis of checkpoint blockade response in advanced non-small cell lung cancer

Author

Ravi, Arvind, Hellmann, Matthew D., Arniella, Monica B., Holton, Mark, Freeman, Samuel S., Naranbhai, Vivek, Stewart, Chip, Leshchiner, Ignaty, Kim, Jaegil, Akiyama, Yo, Griffin, Aaron T., Vokes, Natalie I., Sakhi, Mustafa, Kamesan, Vashine, Rizvi, Hira, Ricciuti, Biagio, Forde, Patrick M., Anagnostou, Valsamo, Riess, Jonathan W., Gibbons, Don L., Pennell, Nathan A., Velcheti, Vamsidhar, Digumarthy, Subba R., Mino-Kenudson, Mari, Califano, Andrea, Heymach, John V., Herbst, Roy S., Brahmer, Julie R., Schalper, Kurt A., Velculescu, Victor E., Henick, Brian S., Rizvi, Naiyer, Jänne, Pasi A., Awad, Mark M., Chow, Andrew, Greenbaum, Benjamin D., Luksza, Marta, Shaw, Alice T., Wolchok, Jedd, Hacohen, Nir, Getz, Gad, and Gainor, Justin F.

Published
2023
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6. Clinical and molecular features of acquired resistance to immunotherapy in non-small cell lung cancer

Author

Memon, Danish, Schoenfeld, Adam J., Ye, Darwin, Fromm, George, Rizvi, Hira, Zhang, Xiang, Keddar, Mohamed Reda, Mathew, Divij, Yoo, Kyung Jin, Qiu, Jingya, Lihm, Jayon, Miriyala, Jayalaksmi, Sauter, Jennifer L., Luo, Jia, Chow, Andrew, Bhanot, Umesh K., McCarthy, Caroline, Vanderbilt, Chad M., Liu, Cailian, Abu-Akeel, Mohsen, Plodkowski, Andrew J., McGranahan, Nicholas, Łuksza, Marta, Greenbaum, Benjamin D., Merghoub, Taha, Achour, Ikbel, Barrett, J. Carl, Stewart, Ross, Beltrao, Pedro, Schreiber, Taylor H., Minn, Andy J., Miller, Martin L., and Hellmann, Matthew D.

Published
2024
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7. Neoantigen quality predicts immunoediting in survivors of pancreatic cancer

Author

Łuksza, Marta, Sethna, Zachary M., Rojas, Luis A., Lihm, Jayon, Bravi, Barbara, Elhanati, Yuval, Soares, Kevin, Amisaki, Masataka, Dobrin, Anton, Hoyos, David, Guasp, Pablo, Zebboudj, Abderezak, Yu, Rebecca, Chandra, Adrienne Kaya, Waters, Theresa, Odgerel, Zagaa, Leung, Joanne, Kappagantula, Rajya, Makohon-Moore, Alvin, Johns, Amber, Gill, Anthony, Gigoux, Mathieu, Wolchok, Jedd, Merghoub, Taha, Sadelain, Michel, Patterson, Erin, Monasson, Remi, Mora, Thierry, Walczak, Aleksandra M., Cocco, Simona, Iacobuzio-Donahue, Christine, Greenbaum, Benjamin D., and Balachandran, Vinod P.

Published
2022
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8. Fundamental immune–oncogenicity trade-offs define driver mutation fitness

Author

Hoyos, David, Zappasodi, Roberta, Schulze, Isabell, Sethna, Zachary, de Andrade, Kelvin César, Bajorin, Dean F., Bandlamudi, Chaitanya, Callahan, Margaret K., Funt, Samuel A., Hadrup, Sine R., Holm, Jeppe S., Rosenberg, Jonathan E., Shah, Sohrab P., Vázquez-García, Ignacio, Weigelt, Britta, Wu, Michelle, Zamarin, Dmitriy, Campitelli, Laura F., Osborne, Edward J., Klinger, Mark, Robins, Harlan S., Khincha, Payal P., Savage, Sharon A., Balachandran, Vinod P., Wolchok, Jedd D., Hellmann, Matthew D., Merghoub, Taha, Levine, Arnold J., Łuksza, Marta, and Greenbaum, Benjamin D.

Published
2022
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9. Y RNAs are conserved endogenous RIG-I ligands across RNA virus infection and are targeted by HIV-1

Author

Vabret, Nicolas, Najburg, Valérie, Solovyov, Alexander, Gopal, Ramya, McClain, Christopher, Šulc, Petr, Balan, Sreekumar, Rahou, Yannis, Beauclair, Guillaume, Chazal, Maxime, Varet, Hugo, Legendre, Rachel, Sismeiro, Odile, Sanchez David, Raul Y., Chauveau, Lise, Jouvenet, Nolwenn, Markowitz, Martin, van der Werf, Sylvie, Schwartz, Olivier, Tangy, Frédéric, Bhardwaj, Nina, Greenbaum, Benjamin D., and Komarova, Anastassia V.

Published
2022
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10. Radiation therapy enhances immunotherapy response in microsatellite stable colorectal and pancreatic adenocarcinoma in a phase II trial

Author

Parikh, Aparna R., Szabolcs, Annamaria, Allen, Jill N., Clark, Jeffrey W., Wo, Jennifer Y., Raabe, Michael, Thel, Hannah, Hoyos, David, Mehta, Arnav, Arshad, Sanya, Lieb, David J., Drapek, Lorraine C., Blaszkowsky, Lawrence S., Giantonio, Bruce J., Weekes, Colin D., Zhu, Andrew X., Goyal, Lipika, Nipp, Ryan D., Dubois, Jon S., Van Seventer, Emily E., Foreman, Bronwen E., Matlack, Lauren E., Ly, Leilana, Meurer, Jessica A., Hacohen, Nir, Ryan, David P., Yeap, Beow Y., Corcoran, Ryan B., Greenbaum, Benjamin D., Ting, David T., and Hong, Theodore S.

Published
2021
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11. Structures, functions and adaptations of the human LINE-1 ORF2 protein

Author

Baldwin, Eric T., primary, van Eeuwen, Trevor, additional, Hoyos, David, additional, Zalevsky, Arthur, additional, Tchesnokov, Egor P., additional, Sánchez, Roberto, additional, Miller, Bryant D., additional, Di Stefano, Luciano H., additional, Ruiz, Francesc Xavier, additional, Hancock, Matthew, additional, Işik, Esin, additional, Mendez-Dorantes, Carlos, additional, Walpole, Thomas, additional, Nichols, Charles, additional, Wan, Paul, additional, Riento, Kirsi, additional, Halls-Kass, Rowan, additional, Augustin, Martin, additional, Lammens, Alfred, additional, Jestel, Anja, additional, Upla, Paula, additional, Xibinaku, Kera, additional, Congreve, Samantha, additional, Hennink, Maximiliaan, additional, Rogala, Kacper B., additional, Schneider, Anna M., additional, Fairman, Jennifer E., additional, Christensen, Shawn M., additional, Desrosiers, Brian, additional, Bisacchi, Gregory S., additional, Saunders, Oliver L., additional, Hafeez, Nafeeza, additional, Miao, Wenyan, additional, Kapeller, Rosana, additional, Zaller, Dennis M., additional, Sali, Andrej, additional, Weichenrieder, Oliver, additional, Burns, Kathleen H., additional, Götte, Matthias, additional, Rout, Michael P., additional, Arnold, Eddy, additional, Greenbaum, Benjamin D., additional, Romero, Donna L., additional, LaCava, John, additional, and Taylor, Martin S., additional

Published
2023
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13. Satellite repeat RNA expression in epithelial ovarian cancer associates with a tumor-immunosuppressive phenotype

Author

Porter, Rebecca L., Sun, Siyu, Flores, Micayla N., Berzolla, Emily, You, Eunae, Phillips, Ildiko E., Neelima, K.C., Desai, Niyati, Tai, Eric C., Szabolcs, Annamaria, Lang, Evan R., Pankaj, Amaya, Raabe, Michael J., Thapar, Vishal, Xu, Katherine H., Nieman, Linda T., Rabe, Daniel C., Kolin, David L., Stover, Elizabeth H., Pepin, David, Stott, Shannon L., Deshpande, Vikram, Liu, Joyce F., Solovyov, Alexander, Matulonis, Ursula A., Greenbaum, Benjamin D., and Ting, David T.

Subjects
Immune response -- Genetic aspects -- Health aspects, RNA -- Physiological aspects -- Health aspects, Ovarian cancer -- Genetic aspects -- Development and progression, Health care industry
Abstract

Aberrant expression of viral-like repeat elements is a common feature of epithelial cancers, and the substantial diversity of repeat species provides a distinct view of the cancer transcriptome. Repeatome profiling across ovarian, pancreatic, and colorectal cell lines identifies distinct clustering independent of tissue origin that is seen with coding gene analysis. Deeper analysis of ovarian cancer cell lines demonstrated that human satellite II (HSATII) satellite repeat expression was highly associated with epithelial-mesenchymal transition (EMT) and anticorrelated with IFN-response genes indicative of a more aggressive phenotype. SATII expression--and its correlation with EMT and anticorrelation with IFN-response genes-- was also found in ovarian cancer RNA-Seq data and was associated with significantly shorter survival in a second independent cohort of patients with ovarian cancer. Repeat RNAs were enriched in tumor-derived extracellular vesicles capable of stimulating monocyte-derived macrophages, demonstrating a mechanism that alters the tumor microenvironment with these viral-like sequences. Targeting of HSATII with antisense locked nucleic acids stimulated IFN response and induced MHC I expression in ovarian cancer cell lines, highlighting a potential strategy of modulating the repeatome to reestablish antitumor cell immune surveillance., Introduction Repetitive elements make up approximately 50% of the human genome (1, 2), and their aberrant expression has been described across a wide range ofcancers (3-5). Repeat suppression is achieved [...]

Published
2022
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14. Author Correction: Fundamental immune–oncogenicity trade-offs define driver mutation fitness

Author

Hoyos, David, Zappasodi, Roberta, Schulze, Isabell, Sethna, Zachary, de Andrade, Kelvin César, Bajorin, Dean F., Bandlamudi, Chaitanya, Callahan, Margaret K., Funt, Samuel A., Hadrup, Sine R., Holm, Jeppe S., Rosenberg, Jonathan E., Shah, Sohrab P., Vázquez-García, Ignacio, Weigelt, Britta, Wu, Michelle, Zamarin, Dmitriy, Campitelli, Laura F., Osborne, Edward J., Klinger, Mark, Robins, Harlan S., Khincha, Payal P., Savage, Sharon A., Balachandran, Vinod P., Wolchok, Jedd D., Hellmann, Matthew D., Merghoub, Taha, Levine, Arnold J., Łuksza, Marta, and Greenbaum, Benjamin D.

Published
2022
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16. Tissue-specific features of the T cell repertoire after allogeneic hematopoietic cell transplantation in human and mouse

Author

DeWolf, Susan, primary, Elhanati, Yuval, additional, Nichols, Katherine, additional, Waters, Nicholas R., additional, Nguyen, Chi L., additional, Slingerland, John B., additional, Rodriguez, Natasia, additional, Lyudovyk, Olga, additional, Giardina, Paul A., additional, Kousa, Anastasia I., additional, Andrlová, Hana, additional, Ceglia, Nick, additional, Fei, Teng, additional, Kappagantula, Rajya, additional, Li, Yanyun, additional, Aleynick, Nathan, additional, Baez, Priscilla, additional, Murali, Rajmohan, additional, Hayashi, Akimasa, additional, Lee, Nicole, additional, Gipson, Brianna, additional, Rangesa, Madhumitha, additional, Katsamakis, Zoe, additional, Dai, Anqi, additional, Blouin, Amanda G., additional, Arcila, Maria, additional, Masilionis, Ignas, additional, Chaligne, Ronan, additional, Ponce, Doris M., additional, Landau, Heather J., additional, Politikos, Ioannis, additional, Tamari, Roni, additional, Hanash, Alan M., additional, Jenq, Robert R., additional, Giralt, Sergio A., additional, Markey, Kate A., additional, Zhang, Yanming, additional, Perales, Miguel-Angel, additional, Socci, Nicholas D., additional, Greenbaum, Benjamin D., additional, Iacobuzio-Donahue, Christine A., additional, Hollmann, Travis J., additional, van den Brink, Marcel R. M., additional, and Peled, Jonathan U., additional

Published
2023
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17. Cancer cells co-evolve with retrotransposons to mitigate viral mimicry

Author

Sun, Siyu, primary, Hong, Jungeui, additional, You, Eunae, additional, Tsanov, Kaloyan M., additional, Chacon-Barahona, Jonathan, additional, Gioacchino, Andrea Di, additional, Hoyos, David, additional, Li, Hao, additional, Jiang, Hua, additional, Ly, Han, additional, Marhon, Sajid A., additional, Murali, Rajmohan, additional, Chanda, Pharto, additional, Karacay, Ali, additional, Vabret, Nicolas, additional, Carvalho, Daniel D., additional, LaCava, John, additional, Lowe, Scott W., additional, Ting, David T., additional, Iacobuzio-Donahue, Christine A., additional, Solovyov, Alexander, additional, and Greenbaum, Benjamin D., additional

Published
2023
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18. Mechanism-guided quantification of LINE-1 reveals p53 regulation of both retrotransposition and transcription

Author

Solovyov, Alexander, primary, Behr, Julie M, additional, Hoyos, David, additional, Banks, Eric M, additional, Drong, Alexander W, additional, Zhong, Jimmy Z, additional, Garcia-Rivera, Enrique, additional, McKerrow, Wilson, additional, Chu, Chong, additional, Zaller, Dennis M, additional, Fromer, Menachem, additional, and Greenbaum, Benjamin D., additional

Published
2023
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19. Supplementary Data from Reverse Transcriptase Inhibition Disrupts Repeat Element Life Cycle in Colorectal Cancer

Author

Rajurkar, Mihir, primary, Parikh, Aparna R., primary, Solovyov, Alexander, primary, You, Eunae, primary, Kulkarni, Anupriya S., primary, Chu, Chong, primary, Xu, Katherine H., primary, Jaicks, Christopher, primary, Taylor, Martin S., primary, Wu, Connie, primary, Alexander, Katherine A., primary, Good, Charly R., primary, Szabolcs, Annamaria, primary, Gerstberger, Stefanie, primary, Tran, Antuan V., primary, Xu, Nova, primary, Ebright, Richard Y., primary, Van Seventer, Emily E., primary, Vo, Kevin D., primary, Tai, Eric C., primary, Lu, Chenyue, primary, Joseph-Chazan, Jasmin, primary, Raabe, Michael J., primary, Nieman, Linda T., primary, Desai, Niyati, primary, Arora, Kshitij S., primary, Ligorio, Matteo, primary, Thapar, Vishal, primary, Cohen, Limor, primary, Garden, Padric M., primary, Senussi, Yasmeen, primary, Zheng, Hui, primary, Allen, Jill N., primary, Blaszkowsky, Lawrence S., primary, Clark, Jeffrey W., primary, Goyal, Lipika, primary, Wo, Jennifer Y., primary, Ryan, David P., primary, Corcoran, Ryan B., primary, Deshpande, Vikram, primary, Rivera, Miguel N., primary, Aryee, Martin J., primary, Hong, Theodore S., primary, Berger, Shelley L., primary, Walt, David R., primary, Burns, Kathleen H., primary, Park, Peter J., primary, Greenbaum, Benjamin D., primary, and Ting, David T., primary

Published
2023
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20. Data from Reverse Transcriptase Inhibition Disrupts Repeat Element Life Cycle in Colorectal Cancer

Author

Rajurkar, Mihir, primary, Parikh, Aparna R., primary, Solovyov, Alexander, primary, You, Eunae, primary, Kulkarni, Anupriya S., primary, Chu, Chong, primary, Xu, Katherine H., primary, Jaicks, Christopher, primary, Taylor, Martin S., primary, Wu, Connie, primary, Alexander, Katherine A., primary, Good, Charly R., primary, Szabolcs, Annamaria, primary, Gerstberger, Stefanie, primary, Tran, Antuan V., primary, Xu, Nova, primary, Ebright, Richard Y., primary, Van Seventer, Emily E., primary, Vo, Kevin D., primary, Tai, Eric C., primary, Lu, Chenyue, primary, Joseph-Chazan, Jasmin, primary, Raabe, Michael J., primary, Nieman, Linda T., primary, Desai, Niyati, primary, Arora, Kshitij S., primary, Ligorio, Matteo, primary, Thapar, Vishal, primary, Cohen, Limor, primary, Garden, Padric M., primary, Senussi, Yasmeen, primary, Zheng, Hui, primary, Allen, Jill N., primary, Blaszkowsky, Lawrence S., primary, Clark, Jeffrey W., primary, Goyal, Lipika, primary, Wo, Jennifer Y., primary, Ryan, David P., primary, Corcoran, Ryan B., primary, Deshpande, Vikram, primary, Rivera, Miguel N., primary, Aryee, Martin J., primary, Hong, Theodore S., primary, Berger, Shelley L., primary, Walt, David R., primary, Burns, Kathleen H., primary, Park, Peter J., primary, Greenbaum, Benjamin D., primary, and Ting, David T., primary

Published
2023
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22. Supplementary Figure from Reverse Transcriptase Inhibition Disrupts Repeat Element Life Cycle in Colorectal Cancer

Author

Rajurkar, Mihir, primary, Parikh, Aparna R., primary, Solovyov, Alexander, primary, You, Eunae, primary, Kulkarni, Anupriya S., primary, Chu, Chong, primary, Xu, Katherine H., primary, Jaicks, Christopher, primary, Taylor, Martin S., primary, Wu, Connie, primary, Alexander, Katherine A., primary, Good, Charly R., primary, Szabolcs, Annamaria, primary, Gerstberger, Stefanie, primary, Tran, Antuan V., primary, Xu, Nova, primary, Ebright, Richard Y., primary, Van Seventer, Emily E., primary, Vo, Kevin D., primary, Tai, Eric C., primary, Lu, Chenyue, primary, Joseph-Chazan, Jasmin, primary, Raabe, Michael J., primary, Nieman, Linda T., primary, Desai, Niyati, primary, Arora, Kshitij S., primary, Ligorio, Matteo, primary, Thapar, Vishal, primary, Cohen, Limor, primary, Garden, Padric M., primary, Senussi, Yasmeen, primary, Zheng, Hui, primary, Allen, Jill N., primary, Blaszkowsky, Lawrence S., primary, Clark, Jeffrey W., primary, Goyal, Lipika, primary, Wo, Jennifer Y., primary, Ryan, David P., primary, Corcoran, Ryan B., primary, Deshpande, Vikram, primary, Rivera, Miguel N., primary, Aryee, Martin J., primary, Hong, Theodore S., primary, Berger, Shelley L., primary, Walt, David R., primary, Burns, Kathleen H., primary, Park, Peter J., primary, Greenbaum, Benjamin D., primary, and Ting, David T., primary

Published
2023
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23. TCRi: Information theoretic metrics for single cell RNA and TCR sequencing in cancer

Author

Ceglia, Nicholas, primary, Sethna, Zachary M., additional, Elhanati, Yuval, additional, Burman, Bharat, additional, Chow, Andrew, additional, Zamarin, Dmitriy, additional, DeWolf, Susan, additional, Shahid, Sanam, additional, Bojilova, Viktoria, additional, Rusk, Nicole, additional, Balachandran, Vinod P., additional, McPherson, Andrew, additional, Shah, Sohrab P., additional, and Greenbaum, Benjamin D., additional

Published
2022
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25. Systemic and Oligo-Acquired Resistance to PD-(L)1 Blockade in Lung Cancer

Author

Schoenfeld, Adam J., primary, Rizvi, Hira A., additional, Memon, Danish, additional, Shaverdian, Narek, additional, Bott, Matthew J., additional, Sauter, Jennifer L., additional, Tsai, C. Jillian, additional, Lihm, Jayon, additional, Hoyos, David, additional, Plodkowski, Andrew J., additional, Perez-Johnston, Rocio, additional, Sawan, Peter, additional, Egger, Jacklynn V., additional, Greenbaum, Benjamin D., additional, Rimner, Andreas, additional, Riely, Gregory J., additional, Rudin, Charles M., additional, Rusch, Valerie W., additional, Gomez, Daniel R., additional, and Hellmann, Matthew D., additional

Published
2022
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26. Integrative Analysis of Checkpoint Blockade Response in Advanced Non-Small Cell Lung Cancer

Author

Ravi, Arvind, primary, Gainor, Justin F, additional, Arniella, Monica B, additional, Holton, Mark, additional, Freeman, Samuel S, additional, Stewart, Chip, additional, Leshchiner, Ignaty, additional, Kim, Jaegil, additional, Akiyama, Yo, additional, Griffin, Aaron T, additional, Vokes, Natalie I, additional, Sakhi, Mustafa, additional, Kamesan, Vashine, additional, Rizvi, Hira, additional, Ricciuti, Biagio, additional, Forde, Patrick M, additional, Anagnostou, Valsamo, additional, Reiss, Jonathan W, additional, Gibbons, Don L, additional, Pennell, Nathan A, additional, Velcheti, Vamsidhar, additional, Digumarthy, Subbha R, additional, Mino-Kenudson, Mari, additional, Califano, Andrea, additional, Heymach, John V, additional, Herbst, Roy S, additional, Brahmer, Julie R, additional, Schalper, Kurt A, additional, Velculescu, Victor E, additional, Henick, Brian S, additional, Rizvi, Naiyer, additional, Janne, Pasi A, additional, Awad, Mark M, additional, Chow, Andrew, additional, Greenbaum, Benjamin D, additional, Luksza, Marta, additional, Shaw, Alice T, additional, Wolchok, Jedd, additional, Hacohen, Nir, additional, Getz, Gad, additional, and Hellmann, Matthew D, additional

Published
2022
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27. Reverse Transcriptase Inhibition Disrupts Repeat Element Life Cycle in Colorectal Cancer

Author

Rajurkar, Mihir, primary, Parikh, Aparna R., additional, Solovyov, Alexander, additional, You, Eunae, additional, Kulkarni, Anupriya S., additional, Chu, Chong, additional, Xu, Katherine H., additional, Jaicks, Christopher, additional, Taylor, Martin S., additional, Wu, Connie, additional, Alexander, Katherine A., additional, Good, Charly R., additional, Szabolcs, Annamaria, additional, Gerstberger, Stefanie, additional, Tran, Antuan V., additional, Xu, Nova, additional, Ebright, Richard Y., additional, Van Seventer, Emily E., additional, Vo, Kevin D., additional, Tai, Eric C., additional, Lu, Chenyue, additional, Joseph-Chazan, Jasmin, additional, Raabe, Michael J., additional, Nieman, Linda T., additional, Desai, Niyati, additional, Arora, Kshitij S., additional, Ligorio, Matteo, additional, Thapar, Vishal, additional, Cohen, Limor, additional, Garden, Padric M., additional, Senussi, Yasmeen, additional, Zheng, Hui, additional, Allen, Jill N., additional, Blaszkowsky, Lawrence S., additional, Clark, Jeffrey W., additional, Goyal, Lipika, additional, Wo, Jennifer Y., additional, Ryan, David P., additional, Corcoran, Ryan B., additional, Deshpande, Vikram, additional, Rivera, Miguel N., additional, Aryee, Martin J., additional, Hong, Theodore S., additional, Berger, Shelley L., additional, Walt, David R., additional, Burns, Kathleen H., additional, Park, Peter J., additional, Greenbaum, Benjamin D., additional, and Ting, David T., additional

Published
2022
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28. Impaired Humoral Immunity Is Associated With Prolonged COVID-19 Despite Robust CD8 T-Cell Responses

Author

Lyudovyk, Olga, primary, Kim, Justin Y., additional, Qualls, David, additional, Hwee, Madeline A., additional, Boutemine, Sawsan R., additional, Elhanati, Yuval, additional, Solovyov, Alexander, additional, Douglas, Melanie, additional, Chen, Eunise, additional, Babady, Ngolela Esther, additional, Ramanathan, Lakshmi, additional, Vedantam, Pallavi, additional, Gouma, Sigrid, additional, Wong, Philip, additional, Hensley, Scott E., additional, Greenbaum, Benjamin D., additional, Huang, Alexander, additional, and Vardhana, Santosha Adipudi, additional

Published
2022
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29. Tissue-Specific Landscape of the Human T Cell Repertoire in Graft-Versus-Host Disease

Author

DeWolf, Susan, primary, Nichols, Katherine, additional, Elhanati, Yuval, additional, Nguyen, Chi L., additional, Waters, Nicholas R., additional, Rodriguez, Natasia, additional, Giardina, Paul A., additional, Slingerland, John B., additional, Andrlová, Hana, additional, Kappagantula, Rajya, additional, Li, Yanyun, additional, Baez, Priscilla, additional, Murali, Rajmohan, additional, Hayashi, Akimasa, additional, Lee, Nicole, additional, Dai, Anqi, additional, Kousa, Anastasia I., additional, Blouin, Amanda G., additional, Ponce, Doris M., additional, Landau, Heather J., additional, Politikos, Ioannis, additional, Tamari, Roni, additional, Hanash, Alan M., additional, Jenq, Robert R., additional, Giralt, Sergio A., additional, Markey, Kate A., additional, Zhang, Yanming, additional, Perales, Miguel-Angel, additional, Socci, Nicholas D., additional, Greenbaum, Benjamin D., additional, Iacobuzio-Donahue, Christine, additional, Hollmann, Travis J., additional, van den Brink, Marcel R.M., additional, and Peled, Jonathan U., additional

Published
2022
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31. Abstract PR-003: High quality neoantigens are immunoedited in long-term pancreatic cancer survivors

Author

Rojas, Luis A., primary, Łuksza, Marta, additional, Sethna, Zachary M., additional, Soares, Kevin, additional, Leung, Joanne, additional, Lihm, Jayon, additional, Hoyos, David, additional, Dobrin, Anton, additional, Kappagantula, Rajya, additional, Makohon-Moore, Alvin, additional, Johns, Amber, additional, Gill, Anthony, additional, Amisaki, Masataka, additional, Guasp, Pablo, additional, Zebboudj, Abderezak, additional, Yu, Rebecca, additional, Chandra, Adrienne Kaya, additional, Odgerel, Zagaa, additional, Sadelain, Michel, additional, Patterson, Erin, additional, Iacobuzio-Donahue, Christine, additional, Greenbaum, Benjamin D., additional, and Balachandran, Vinod P., additional

Published
2021
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32. Repeats Mimic Pathogen-Associated Patterns Across a Vast Evolutionary Landscape

Author

Šulc, Petr, primary, Di Gioacchino, Andrea, additional, Solovyov, Alexander, additional, Marhon, Sajid A, additional, Sun, Siyu, additional, Lindholm, Haavard, additional, Chen, Raymond, additional, Hosseini, Amir, additional, Jiang, Hua, additional, Ly, Bao-Han, additional, Mehdipour, Parinaz, additional, Abdel-Wahab, Omar I., additional, Vabret, Nicolas, additional, LaCava, John, additional, De Carvalho, Daniel, additional, Monasson, Rémi, additional, Cocco, Simona, additional, and Greenbaum, Benjamin D., additional

Published
2021
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33. sgDI-tector: defective interfering viral genome bioinformatics for detection of coronavirus subgenomic RNAs

Author

Di Gioacchino, Andrea, Legendre, Rachel, Rahou, Yannis, Najburg, Valérie, Charneau, Pierre, Greenbaum, Benjamin D., Tangy, Frédéric, van der Werf, Sylvie, Cocco, Simona, and Komarova, Anastassia V.

Abstract

Coronavirus RNA-dependent RNA polymerases produce subgenomic RNAs (sgRNAs) that encode viral structural and accessory proteins. User-friendly bioinformatic tools to detect and quantify sgRNA production are urgently needed to study the growing number of next-generation sequencing (NGS) data of SARS-CoV-2. We introduced sgDI-tector to identify and quantify sgRNA in SARS-CoV-2 NGS data. sgDI-tector allowed detection of sgRNA without initial knowledge of the transcription-regulatory sequences. We produced NGS data and successfully detected the nested set of sgRNAs with the ranking M > ORF3a > N>ORF6 > ORF7a > ORF8 > S > E>ORF7b. We also compared the level of sgRNA production with other types of viral RNA products such as defective interfering viral genomes.

Published
2022
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34. Disruption of cellular plasticity by repeat RNAs in human pancreatic cancer.

Author

You E, Danaher P, Lu C, Sun S, Zou L, Phillips IE, Rojas AS, Ho NI, Song Y, Raabe MJ, Xu KH, Richieri PM, Li H, Aston N, Porter RL, Patel BK, Nieman LT, Schurman N, Hudson BM, North K, Church SE, Deshpande V, Liss AS, Kim TK, Cui Y, Kim Y, Greenbaum BD, Aryee MJ, and Ting DT

Abstract

Aberrant expression of repeat RNAs in pancreatic ductal adenocarcinoma (PDAC) mimics viral-like responses with implications on tumor cell state and the response of the surrounding microenvironment. To better understand the relationship of repeat RNAs in human PDAC, we performed spatial molecular imaging at single-cell resolution in 46 primary tumors, revealing correlations of high repeat RNA expression with alterations in epithelial state in PDAC cells and myofibroblast phenotype in cancer-associated fibroblasts (CAFs). This loss of cellular identity is observed with dosing of extracellular vesicles (EVs) and individual repeat RNAs of PDAC and CAF cell culture models pointing to cell-cell intercommunication of these viral-like elements. Differences in PDAC and CAF responses are driven by distinct innate immune signaling through interferon regulatory factor 3 (IRF3). The cell-context-specific viral-like responses to repeat RNAs provide a mechanism for modulation of cellular plasticity in diverse cell types in the PDAC microenvironment., Competing Interests: Declaration of interests D.T.T. and B.D.G. are co-founders with equity and consulting fees from ROME Therapeutics, a company developing drugs targeting repetitive elements, but this work was not supported by ROME Therapeutics. D.T.T. received in kind research support and a speaking honorarium from NanoString Technologies, and in kind research support from ACD-Biotechne, which was used in this work. M.J.A. is a co-founder of, owns equity in, and receives consulting fees from SeQure Dx, unrelated to this work. M.J.A. receives consulting fees from Chroma Medicine, unrelated to this work. P.D., N.S., B.M.H., K.N., S.E.C., T.K.K., Y.C., and Y.K. are or were employees of NanoString Technologies. D.T.T. has received consulting fees from PanTher Therapeutics, AstraZeneca, Sonata Therapeutics, Moderna, abrdn, Astellas, and Leica Biosystems Imaging; is a founder and has equity in PanTher Therapeutics and TellBio, Inc.; and is on the scientific advisory board with equity for ImproveBio, Inc., which are not related to this work. D.T.T. receives research support from Sanofi, AVA LifeScience GmbH, and Incyte, which was not used in this work. B.D.G. is a consultant or received honoraria for Darwin Health, Merck, PMV Pharma, Merck, Bristol-Meyers Squibb, and Chugai Pharmaceuticals and has research funding from Bristol-Meyers Squibb., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Published
2024
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35. Distinct genomic and immunologic tumor evolution in germline TP53 -driven breast cancers.

Author

Boruah N, Hoyos D, Moses R, Hausler R, Desai H, Le AN, Good M, Kelly G, Raghavakaimal A, Tayeb M, Narasimhamurthy M, Doucette A, Gabriel P, Feldman MJ, Park J, de Rodas ML, Schalper KA, Goldfarb SB, Nayak A, Levine AJ, Greenbaum BD, and Maxwell KN

Abstract

Pathogenic germline TP53 alterations cause Li-Fraumeni Syndrome (LFS), and breast cancer is the most common cancer in LFS females. We performed first of its kind multimodal analysis of LFS breast cancer (LFS-BC) compared to sporadic premenopausal BC. Nearly all LFS-BC underwent biallelic loss of TP53 with no recurrent oncogenic variants except ERBB2 (HER2) amplification. Compared to sporadic BC, in situ and invasive LFS-BC exhibited a high burden of short amplified aneuploid segments (SAAS). Pro-apoptotic p53 target genes BAX and TP53I3 failed to be up-regulated in LFS-BC as was seen in sporadic BC compared to normal breast tissue. LFS-BC had lower CD8+ T-cell infiltration compared to sporadic BC yet higher levels of proliferating cytotoxic T-cells. Within LFS-BC, progression from in situ to invasive BC was marked by an increase in chromosomal instability with a decrease in proliferating cytotoxic T-cells. Our study uncovers critical events in mutant p53-driven tumorigenesis in breast tissue., Competing Interests: NB, RM, RH, HD, AL, MG, GK, AR, MT, MLR and KNM report no conflicts of interest. KAS reports fees for consultant services, advisor or speaker from Clinica Alemana Santiago, Shattuck Labs, AstraZeneca, Takeda, Torque/Repertoire Therapeutics, CSRlife, Agenus, Genmab, Sanofi, Parthenon Therapeutics, Bristol-Myers Squibb, Roche, Molecular Templates, Merck, PeerView, PER and Forefront Collaborative. KAS reports research funding from Tesaro/GSK, Moderna Inc., Takeda, Surface Oncology, Merck, Bristol-Myers Squibb, AstraZeneca, Ribon Therapeutics, Eli Lilly, Boehringer-Ingelheim, Roche and Akoya Biosciences. AJL is founder and shareholder of PMV Pharma, a biotech company that works on reactivator of mutant p53. B.G. has received honoraria for speaking engagements from Merck, Bristol Meyers Squibb, and Chugai Pharmaceuticals; has received research funding from Bristol Meyers Squibb and Merck; and has been a compensated consultant for Darwin Health, Merck, PMV Pharma, Shennon Biotechnologies, and ROME Therapeutics of which he is a co-founder.

Published
2024
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36. Cancer cells co-evolve with retrotransposons to mitigate viral mimicry.

Author

Sun S, Hong J, You E, Tsanov KM, Chacon-Barahona J, Gioacchino AD, Hoyos D, Li H, Jiang H, Ly H, Marhon S, Murali R, Chanda P, Karacay A, Vabret N, De Carvalho DD, LaCava J, Lowe SW, Ting DT, Iacobuzio-Donahue CA, Solovyov A, and Greenbaum BD

Abstract

Overexpression of repetitive elements is an emerging hallmark of human cancers 1 . Diverse repeats can mimic viruses by replicating within the cancer genome through retrotransposition, or presenting pathogen-associated molecular patterns (PAMPs) to the pattern recognition receptors (PRRs) of the innate immune system 2-5 . Yet, how specific repeats affect tumor evolution and shape the tumor immune microenvironment (TME) in a pro- or anti-tumorigenic manner remains poorly defined. Here, we integrate whole genome and total transcriptome data from a unique autopsy cohort of multiregional samples collected in pancreatic ductal adenocarcinoma (PDAC) patients, into a comprehensive evolutionary analysis. We find that more recently evolved S hort I nterspersed N uclear E lements (SINE), a family of retrotransposable repeats, are more likely to form immunostimulatory double-strand RNAs (dsRNAs). Consequently, younger SINEs are strongly co-regulated with RIG-I like receptor associated type-I interferon genes but anti-correlated with pro-tumorigenic macrophage infiltration. We discover that immunostimulatory SINE expression in tumors is regulated by either L ong I nterspersed N uclear E lements 1 (LINE1/L1) mobility or ADAR1 activity in a TP53 mutation dependent manner. Moreover, L1 retrotransposition activity tracks with tumor evolution and is associated with TP53 mutation status. Altogether, our results suggest pancreatic tumors actively evolve to modulate immunogenic SINE stress and induce pro-tumorigenic inflammation. Our integrative, evolutionary analysis therefore illustrates, for the first time, how dark matter genomic repeats enable tumors to co-evolve with the TME by actively regulating viral mimicry to their selective advantage.

Published
2023
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