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2. Euclid. I. Overview of the Euclid mission

Author

Euclid Collaboration, Mellier, Y., Abdurro'uf, Barroso, J. A. Acevedo, Achúcarro, A., Adamek, J., Adam, R., Addison, G. E., Aghanim, N., Aguena, M., Ajani, V., Akrami, Y., Al-Bahlawan, A., Alavi, A., Albuquerque, I. S., Alestas, G., Alguero, G., Allaoui, A., Allen, S. W., Allevato, V., Alonso-Tetilla, A. V., Altieri, B., Alvarez-Candal, A., Alvi, S., Amara, A., Amendola, L., Amiaux, J., Andika, I. T., Andreon, S., Andrews, A., Angora, G., Angulo, R. E., Annibali, F., Anselmi, A., Anselmi, S., Arcari, S., Archidiacono, M., Aricò, G., Arnaud, M., Arnouts, S., Asgari, M., Asorey, J., Atayde, L., Atek, H., Atrio-Barandela, F., Aubert, M., Aubourg, E., Auphan, T., Auricchio, N., Aussel, B., Aussel, H., Avelino, P. P., Avgoustidis, A., Avila, S., Awan, S., Azzollini, R., Baccigalupi, C., Bachelet, E., Bacon, D., Baes, M., Bagley, M. B., Bahr-Kalus, B., Balaguera-Antolinez, A., Balbinot, E., Balcells, M., Baldi, M., Baldry, I., Balestra, A., Ballardini, M., Ballester, O., Balogh, M., Bañados, E., Barbier, R., Bardelli, S., Baron, M., Barreiro, T., Barrena, R., Barriere, J. -C., Barros, B. J., Barthelemy, A., Bartolo, N., Basset, A., Battaglia, P., Battisti, A. J., Baugh, C. M., Baumont, L., Bazzanini, L., Beaulieu, J. -P., Beckmann, V., Belikov, A. N., Bel, J., Bellagamba, F., Bella, M., Bellini, E., Benabed, K., Bender, R., Benevento, G., Bennett, C. L., Benson, K., Bergamini, P., Bermejo-Climent, J. R., Bernardeau, F., Bertacca, D., Berthe, M., Berthier, J., Bethermin, M., Beutler, F., Bevillon, C., Bhargava, S., Bhatawdekar, R., Bianchi, D., Bisigello, L., Biviano, A., Blake, R. P., Blanchard, A., Blazek, J., Blot, L., Bosco, A., Bodendorf, C., Boenke, T., Böhringer, H., Boldrini, P., Bolzonella, M., Bonchi, A., Bonici, M., Bonino, D., Bonino, L., Bonvin, C., Bon, W., Booth, J. T., Borgani, S., Borlaff, A. S., Borsato, E., Bose, B., Botticella, M. T., Boucaud, A., Bouche, F., Boucher, J. S., Boutigny, D., Bouvard, T., Bouwens, R., Bouy, H., Bowler, R. A. A., Bozza, V., Bozzo, E., Branchini, E., Brando, G., Brau-Nogue, S., Brekke, P., Bremer, M. N., Brescia, M., Breton, M. -A., Brinchmann, J., Brinckmann, T., Brockley-Blatt, C., Brodwin, M., Brouard, L., Brown, M. L., Bruton, S., Bucko, J., Buddelmeijer, H., Buenadicha, G., Buitrago, F., Burger, P., Burigana, C., Busillo, V., Busonero, D., Cabanac, R., Cabayol-Garcia, L., Cagliari, M. S., Caillat, A., Caillat, L., Calabrese, M., Calabro, A., Calderone, G., Calura, F., Quevedo, B. Camacho, Camera, S., Campos, L., Canas-Herrera, G., Candini, G. P., Cantiello, M., Capobianco, V., Cappellaro, E., Cappelluti, N., Cappi, A., Caputi, K. I., Cara, C., Carbone, C., Cardone, V. F., Carella, E., Carlberg, R. G., Carle, M., Carminati, L., Caro, F., Carrasco, J. M., Carretero, J., Carrilho, P., Duque, J. Carron, Carry, B., Carvalho, A., Carvalho, C. S., Casas, R., Casas, S., Casenove, P., Casey, C. M., Cassata, P., Castander, F. J., Castelao, D., Castellano, M., Castiblanco, L., Castignani, G., Castro, T., Cavet, C., Cavuoti, S., Chabaud, P. -Y., Chambers, K. C., Charles, Y., Charlot, S., Chartab, N., Chary, R., Chaumeil, F., Cho, H., Chon, G., Ciancetta, E., Ciliegi, P., Cimatti, A., Cimino, M., Cioni, M. -R. L., Claydon, R., Cleland, C., Clément, B., Clements, D. L., Clerc, N., Clesse, S., Codis, S., Cogato, F., Colbert, J., Cole, R. E., Coles, P., Collett, T. E., Collins, R. S., Colodro-Conde, C., Colombo, C., Combes, F., Conforti, V., Congedo, G., Conseil, S., Conselice, C. J., Contarini, S., Contini, T., Conversi, L., Cooray, A. R., Copin, Y., Corasaniti, P. -S., Corcho-Caballero, P., Corcione, L., Cordes, O., Corpace, O., Correnti, M., Costanzi, M., Costille, A., Courbin, F., Mifsud, L. Courcoult, Courtois, H. M., Cousinou, M. -C., Covone, G., Cowell, T., Cragg, C., Cresci, G., Cristiani, S., Crocce, M., Cropper, M., Crouzet, P. E, Csizi, B., Cuby, J. -G., Cucchetti, E., Cucciati, O., Cuillandre, J. -C., Cunha, P. A. C., Cuozzo, V., Daddi, E., D'Addona, M., Dafonte, C., Dagoneau, N., Dalessandro, E., Dalton, G. B., D'Amico, G., Dannerbauer, H., Danto, P., Das, I., Da Silva, A., da Silva, R., Doumerg, W. d'Assignies, Daste, G., Davies, J. E., Davini, S., Dayal, P., de Boer, T., Decarli, R., De Caro, B., Degaudenzi, H., Degni, G., de Jong, J. T. A., de la Bella, L. F., de la Torre, S., Delhaise, F., Delley, D., Delucchi, G., De Lucia, G., Denniston, J., De Paolis, F., De Petris, M., Derosa, A., Desai, S., Desjacques, V., Despali, G., Desprez, G., De Vicente-Albendea, J., Deville, Y., Dias, J. D. F., Díaz-Sánchez, A., Diaz, J. J., Di Domizio, S., Diego, J. M., Di Ferdinando, D., Di Giorgio, A. M., Dimauro, P., Dinis, J., Dolag, K., Dolding, C., Dole, H., Sánchez, H. Domínguez, Doré, O., Dournac, F., Douspis, M., Dreihahn, H., Droge, B., Dryer, B., Dubath, F., Duc, P. -A., Ducret, F., Duffy, C., Dufresne, F., Duncan, C. A. J., Dupac, X., Duret, V., Durrer, R., Durret, F., Dusini, S., Ealet, A., Eggemeier, A., Eisenhardt, P. R. M., Elbaz, D., Elkhashab, M. Y., Ellien, A., Endicott, J., Enia, A., Erben, T., Vigo, J. A. Escartin, Escoffier, S., Sanz, I. Escudero, Essert, J., Ettori, S., Ezziati, M., Fabbian, G., Fabricius, M., Fang, Y., Farina, A., Farina, M., Farinelli, R., Farrens, S., Faustini, F., Feltre, A., Ferguson, A. M. N., Ferrando, P., Ferrari, A. G., Ferré-Mateu, A., Ferreira, P. G., Ferreras, I., Ferrero, I., Ferriol, S., Ferruit, P., Filleul, D., Finelli, F., Finkelstein, S. L., Finoguenov, A., Fiorini, B., Flentge, F., Focardi, P., Fonseca, J., Fontana, A., Fontanot, F., Fornari, F., Fosalba, P., Fossati, M., Fotopoulou, S., Fouchez, D., Fourmanoit, N., Frailis, M., Fraix-Burnet, D., Franceschi, E., Franco, A., Franzetti, P., Freihoefer, J., Frenk, C. . S., Frittoli, G., Frugier, P. -A., Frusciante, N., Fumagalli, A., Fumagalli, M., Fumana, M., Fu, Y., Gabarra, L., Galeotta, S., Galluccio, L., Ganga, K., Gao, H., García-Bellido, J., Garcia, K., Gardner, J. P., Garilli, B., Gaspar-Venancio, L. -M., Gasparetto, T., Gautard, V., Gavazzi, R., Gaztanaga, E., Genolet, L., Santos, R. Genova, Gentile, F., George, K., Gerbino, M., Ghaffari, Z., Giacomini, F., Gianotti, F., Gibb, G. P. S., Gillard, W., Gillis, B., Ginolfi, M., Giocoli, C., Girardi, M., Giri, S. K., Goh, L. W. K., Gómez-Alvarez, P., Gonzalez-Perez, V., Gonzalez, A. H., Gonzalez, E. J., Gonzalez, J. C., Beauchamps, S. Gouyou, Gozaliasl, G., Gracia-Carpio, J., Grandis, S., Granett, B. R., Granvik, M., Grazian, A., Gregorio, A., Grenet, C., Grillo, C., Grupp, F., Gruppioni, C., Gruppuso, A., Guerbuez, C., Guerrini, S., Guidi, M., Guillard, P., Gutierrez, C. M., Guttridge, P., Guzzo, L., Gwyn, S., Haapala, J., Haase, J., Haddow, C. R., Hailey, M., Hall, A., Hall, D., Hamaus, N., Haridasu, B. S., Harnois-Déraps, J., Harper, C., Hartley, W. G., Hasinger, G., Hassani, F., Hatch, N. A., Haugan, S. V. H., Häußler, B., Heavens, A., Heisenberg, L., Helmi, A., Helou, G., Hemmati, S., Henares, K., Herent, O., Hernández-Monteagudo, C., Heuberger, T., Hewett, P. C., Heydenreich, S., Hildebrandt, H., Hirschmann, M., Hjorth, J., Hoar, J., Hoekstra, H., Holland, A. D., Holliman, M. S., Holmes, W., Hook, I., Horeau, B., Hormuth, F., Hornstrup, A., Hosseini, S., Hu, D., Hudelot, P., Hudson, M. J., Huertas-Company, M., Huff, E. M., Hughes, A. C. N., Humphrey, A., Hunt, L. K., Huynh, D. D., Ibata, R., Ichikawa, K., Iglesias-Groth, S., Ilbert, O., Ilić, S., Ingoglia, L., Iodice, E., Israel, H., Israelsson, U. E., Izzo, L., Jablonka, P., Jackson, N., Jacobson, J., Jafariyazani, M., Jahnke, K., Jain, B., Jansen, H., Jarvis, M. J., Jasche, J., Jauzac, M., Jeffrey, N., Jhabvala, M., Jimenez-Teja, Y., Muñoz, A. Jimenez, Joachimi, B., Johansson, P. H., Joudaki, S., Jullo, E., Kajava, J. J. E., Kang, Y., Kannawadi, A., Kansal, V., Karagiannis, D., Kärcher, M., Kashlinsky, A., Kazandjian, M. V., Keck, F., Keihänen, E., Kerins, E., Kermiche, S., Khalil, A., Kiessling, A., Kiiveri, K., Kilbinger, M., Kim, J., King, R., Kirkpatrick, C. C., Kitching, T., Kluge, M., Knabenhans, M., Knapen, J. H., Knebe, A., Kneib, J. -P., Kohley, R., Koopmans, L. V. E., Koskinen, H., Koulouridis, E., Kou, R., Kovács, A., Kovačić, I., Kowalczyk, A., Koyama, K., Kraljic, K., Krause, O., Kruk, S., Kubik, B., Kuchner, U., Kuijken, K., Kümmel, M., Kunz, M., Kurki-Suonio, H., Lacasa, F., Lacey, C. G., La Franca, F., Lagarde, N., Lahav, O., Laigle, C., La Marca, A., La Marle, O., Lamine, B., Lam, M. C., Lançon, A., Landt, H., Langer, M., Lapi, A., Larcheveque, C., Larsen, S. S., Lattanzi, M., Laudisio, F., Laugier, D., Laureijs, R., Laurent, V., Lavaux, G., Lawrenson, A., Lazanu, A., Lazeyras, T., Boulc'h, Q. Le, Brun, A. M. C. Le, Brun, V. Le, Leclercq, F., Lee, S., Graet, J. Le, Legrand, L., Leirvik, K. N., Jeune, M. Le, Lembo, M., Mignant, D. Le, Lepinzan, M. D., Lepori, F., Reun, A. Le, Leroy, G., Lesci, G. F., Lesgourgues, J., Leuzzi, L., Levi, M. E., Liaudat, T. I., Libet, G., Liebing, P., Ligori, S., Lilje, P. B., Lin, C. -C., Linde, D., Linder, E., Lindholm, V., Linke, L., Li, S. -S., Liu, S. J., Lloro, I., Lobo, F. S. N., Lodieu, N., Lombardi, M., Lombriser, L., Lonare, P., Longo, G., López-Caniego, M., Lopez, X. Lopez, Alvarez, J. Lorenzo, Loureiro, A., Loveday, J., Lusso, E., Macias-Perez, J., Maciaszek, T., Maggio, G., Magliocchetti, M., Magnard, F., Magnier, E. A., Magro, A., Mahler, G., Mainetti, G., Maino, D., Maiorano, E., Malavasi, N., Mamon, G. A., Mancini, C., Mandelbaum, R., Manera, M., Manjón-García, A., Mannucci, F., Mansutti, O., Outeiro, M. Manteiga, Maoli, R., Maraston, C., Marcin, S., Marcos-Arenal, P., Margalef-Bentabol, B., Marggraf, O., Marinucci, D., Marinucci, M., Markovic, K., Marleau, F. R., Marpaud, J., Martignac, J., Martín-Fleitas, J., Martin-Moruno, P., Martin, E. L., Martinelli, M., Martinet, N., Martin, H., Martins, C. J. A. P., Marulli, F., Massari, D., Massey, R., Masters, D. C., Matarrese, S., Matsuoka, Y., Matthew, S., Maughan, B. J., Mauri, N., Maurin, L., Maurogordato, S., McCarthy, K., McConnachie, A. W., McCracken, H. J., McDonald, I., McEwen, J. D., McPartland, C. J. R., Medinaceli, E., Mehta, V., Mei, S., Melchior, M., Melin, J. -B., Ménard, B., Mendes, J., Mendez-Abreu, J., Meneghetti, M., Mercurio, A., Merlin, E., Metcalf, R. B., Meylan, G., Migliaccio, M., Mignoli, M., Miller, L., Miluzio, M., Milvang-Jensen, B., Mimoso, J. P., Miquel, R., Miyatake, H., Mobasher, B., Mohr, J. J., Monaco, P., Monguió, M., Montoro, A., Mora, A., Dizgah, A. Moradinezhad, Moresco, M., Moretti, C., Morgante, G., Morisset, N., Moriya, T. J., Morris, P. W., Mortlock, D. J., Moscardini, L., Mota, D. F., Mottet, S., Moustakas, L. A., Moutard, T., Müller, T., Munari, E., Murphree, G., Murray, C., Murray, N., Musi, P., Nadathur, S., Nagam, B. C., Nagao, T., Naidoo, K., Nakajima, R., Nally, C., Natoli, P., Navarro-Alsina, A., Girones, D. Navarro, Neissner, C., Nersesian, A., Nesseris, S., Nguyen-Kim, H. N., Nicastro, L., Nichol, R. C., Nielbock, M., Niemi, S. -M., Nieto, S., Nilsson, K., Noller, J., Norberg, P., Nouri-Zonoz, A., Ntelis, P., Nucita, A. A., Nugent, P., Nunes, N. J., Nutma, T., Ocampo, I., Odier, J., Oesch, P. A., Oguri, M., Oliveira, D. Magalhaes, Onoue, M., Oosterbroek, T., Oppizzi, F., Ordenovic, C., Osato, K., Pacaud, F., Pace, F., Padilla, C., Paech, K., Pagano, L., Page, M. J., Palazzi, E., Paltani, S., Pamuk, S., Pandolfi, S., Paoletti, D., Paolillo, M., Papaderos, P., Pardede, K., Parimbelli, G., Parmar, A., Partmann, C., Pasian, F., Passalacqua, F., Paterson, K., Patrizii, L., Pattison, C., Paulino-Afonso, A., Paviot, R., Peacock, J. A., Pearce, F. R., Pedersen, K., Peel, A., Peletier, R. F., Ibanez, M. Pellejero, Pello, R., Penny, M. T., Percival, W. J., Perez-Garrido, A., Perotto, L., Pettorino, V., Pezzotta, A., Pezzuto, S., Philippon, A., Pierre, M., Piersanti, O., Pietroni, M., Piga, L., Pilo, L., Pires, S., Pisani, A., Pizzella, A., Pizzuti, L., Plana, C., Polenta, G., Pollack, J. E., Poncet, M., Pöntinen, M., Pool, P., Popa, L. A., Popa, V., Popp, J., Porciani, C., Porth, L., Potter, D., Poulain, M., Pourtsidou, A., Pozzetti, L., Prandoni, I., Pratt, G. W., Prezelus, S., Prieto, E., Pugno, A., Quai, S., Quilley, L., Racca, G. D., Raccanelli, A., Rácz, G., Radinović, S., Radovich, M., Ragagnin, A., Ragnit, U., Raison, F., Ramos-Chernenko, N., Ranc, C., Rasera, Y., Raylet, N., Rebolo, R., Refregier, A., Reimberg, P., Reiprich, T. H., Renk, F., Renzi, A., Retre, J., Revaz, Y., Reylé, C., Reynolds, L., Rhodes, J., Ricci, F., Ricci, M., Riccio, G., Ricken, S. O., Rissanen, S., Risso, I., Rix, H. -W., Robin, A. C., Rocca-Volmerange, B., Rocci, P. -F., Rodenhuis, M., Rodighiero, G., Monroy, M. Rodriguez, Rollins, R. P., Romanello, M., Roman, J., Romelli, E., Romero-Gomez, M., Roncarelli, M., Rosati, P., Rosset, C., Rossetti, E., Roster, W., Rottgering, H. J. A., Rozas-Fernández, A., Ruane, K., Rubino-Martin, J. A., Rudolph, A., Ruppin, F., Rusholme, B., Sacquegna, S., Sáez-Casares, I., Saga, S., Saglia, R., Sahlén, M., Saifollahi, T., Sakr, Z., Salvalaggio, J., Salvaterra, R., Salvati, L., Salvato, M., Salvignol, J. -C., Sánchez, A. G., Sanchez, E., Sanders, D. B., Sapone, D., Saponara, M., Sarpa, E., Sarron, F., Sartori, S., Sartoris, B., Sassolas, B., Sauniere, L., Sauvage, M., Sawicki, M., Scaramella, R., Scarlata, C., Scharré, L., Schaye, J., Schewtschenko, J. A., Schindler, J. -T., Schinnerer, E., Schirmer, M., Schmidt, F., Schmidt, M., Schneider, A., Schneider, M., Schneider, P., Schöneberg, N., Schrabback, T., Schultheis, M., Schulz, S., Schuster, N., Schwartz, J., Sciotti, D., Scodeggio, M., Scognamiglio, D., Scott, D., Scottez, V., Secroun, A., Sefusatti, E., Seidel, G., Seiffert, M., Sellentin, E., Selwood, M., Semboloni, E., Sereno, M., Serjeant, S., Serrano, S., Setnikar, G., Shankar, F., Sharples, R. M., Short, A., Shulevski, A., Shuntov, M., Sias, M., Sikkema, G., Silvestri, A., Simon, P., Sirignano, C., Sirri, G., Skottfelt, J., Slezak, E., Sluse, D., Smith, G. P., Smith, L. C., Smith, R. E., Smit, S. J. A., Soldano, F., Solheim, B. G. B., Sorce, J. G., Sorrenti, F., Soubrie, E., Spinoglio, L., Mancini, A. Spurio, Stadel, J., Stagnaro, L., Stanco, L., Stanford, S. A., Starck, J. -L., Stassi, P., Steinwagner, J., Stern, D., Stone, C., Strada, P., Strafella, F., Stramaccioni, D., Surace, C., Sureau, F., Suyu, S. H., Swindells, I., Szafraniec, M., Szapudi, I., Taamoli, S., Talia, M., Tallada-Crespí, P., Tanidis, K., Tao, C., Tarrío, P., Tavagnacco, D., Taylor, A. N., Taylor, J. E., Taylor, P. L., Teixeira, E. M., Tenti, M., Idiago, P. Teodoro, Teplitz, H. I., Tereno, I., Tessore, N., Testa, V., Testera, G., Tewes, M., Teyssier, R., Theret, N., Thizy, C., Thomas, P. D., Toba, Y., Toft, S., Toledo-Moreo, R., Tolstoy, E., Tommasi, E., Torbaniuk, O., Torradeflot, F., Tortora, C., Tosi, S., Tosti, S., Trifoglio, M., Troja, A., Trombetti, T., Tronconi, A., Tsedrik, M., Tsyganov, A., Tucci, M., Tutusaus, I., Uhlemann, C., Ulivi, L., Urbano, M., Vacher, L., Vaillon, L., Valageas, P., Valdes, I., Valentijn, E. A., Valenziano, L., Valieri, C., Valiviita, J., Broeck, M. Van den, Vassallo, T., Vavrek, R., Vega-Ferrero, J., Venemans, B., Venhola, A., Ventura, S., Kleijn, G. Verdoes, Vergani, D., Verma, A., Vernizzi, F., Veropalumbo, A., Verza, G., Vescovi, C., Vibert, D., Viel, M., Vielzeuf, P., Viglione, C., Viitanen, A., Villaescusa-Navarro, F., Vinciguerra, S., Visticot, F., Voggel, K., von Wietersheim-Kramsta, M., Vriend, W. J., Wachter, S., Walmsley, M., Walth, G., Walton, D. M., Walton, N. A., Wander, M., Wang, L., Wang, Y., Weaver, J. R., Weller, J., Wetzstein, M., Whalen, D. J., Whittam, I. H., Widmer, A., Wiesmann, M., Wilde, J., Williams, O. R., Winther, H. -A., Wittje, A., Wong, J. H. W., Wright, A. H., Yankelevich, V., Yeung, H. W., Yoon, M., Youles, S., Yung, L. Y. A., Zacchei, A., Zalesky, L., Zamorani, G., Vitorelli, A. Zamorano, Marc, M. Zanoni, Zennaro, M., Zerbi, F. M., Zinchenko, I. A., Zoubian, J., Zucca, E., and Zumalacarregui, M.

Subjects
Astrophysics - Cosmology and Nongalactic Astrophysics, Astrophysics - Astrophysics of Galaxies, Astrophysics - Instrumentation and Methods for Astrophysics
Abstract

The current standard model of cosmology successfully describes a variety of measurements, but the nature of its main ingredients, dark matter and dark energy, remains unknown. Euclid is a medium-class mission in the Cosmic Vision 2015-2025 programme of the European Space Agency (ESA) that will provide high-resolution optical imaging, as well as near-infrared imaging and spectroscopy, over about 14,000 deg^2 of extragalactic sky. In addition to accurate weak lensing and clustering measurements that probe structure formation over half of the age of the Universe, its primary probes for cosmology, these exquisite data will enable a wide range of science. This paper provides a high-level overview of the mission, summarising the survey characteristics, the various data-processing steps, and data products. We also highlight the main science objectives and expected performance., Comment: Accepted for publication in the A&A special issue`Euclid on Sky'

Published
2024

5. Bacterial aggregation facilitates internalin-mediated invasion of Listeria monocytogenes

Author

Liam Feltham, Josephine Moran, Marie Goldrick, Elizabeth Lord, David G. Spiller, Jennifer S. Cavet, Mark Muldoon, Ian. S. Roberts, and Pawel Paszek

Subjects
Listeria monocytogenes, host-pathogen interactions, aggregation, PrfA regulon, live-cell microscopy, Microbiology, QR1-502
Abstract

Dissemination of food-borne L. monocytogenes in the host relies on internalin-mediated invasion, but the underlying invasion strategies remain elusive. Here we use live-cell microscopy to follow single cell interactions between individual human cells and L. monocytogenes and elucidate mechanisms associated with internalin B (InlB)-mediated invasion. We demonstrate that whilst a replicative invasion of nonphagocytic cells is a rare event even at high multiplicities of invasion, L. monocytogenes overcomes this by utilising a strategy relaying on PrfA-mediated ActA-based aggregation. We show that L. monocytogenes forms aggregates in extracellular host cell environment, which promote approximately 5-fold more host cell adhesions than the non-aggregating actA-ΔC mutant (which lacks the C-terminus coding region), with the adhering bacteria inducing 3-fold more intracellular invasions. Aggregation is associated with robust MET tyrosine kinase receptor clustering in the host cells, a hallmark of InlB-mediated invasion, something not observed with the actA-ΔC mutant. Finally, we show via RNA-seq analyses that aggregation involves a global adaptive response to host cell environment (including iron depletion), resulting in metabolic changes in L. monocytogenes and upregulation of the PrfA virulence regulon. Overall, our analyses provide new mechanistic insights into internalin-mediated host-pathogen interactions of L. monocytogenes.

Published
2024
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6. Therapeutic targeting of EP300/CBP by bromodomain inhibition in hematologic malignancies

Author

Nicosia, Luciano, Spencer, Gary J., Brooks, Nigel, Amaral, Fabio M.R., Basma, Naseer J., Chadwick, John A., Revell, Bradley, Wingelhofer, Bettina, Maiques-Diaz, Alba, Sinclair, Oliver, Camera, Francesco, Ciceri, Filippo, Wiseman, Daniel H., Pegg, Neil, West, Will, Knurowski, Tomasz, Frese, Kris, Clegg, Karen, Campbell, Victoria L., Cavet, James, Copland, Mhairi, Searle, Emma, and Somervaille, Tim C.P.

Published
2023
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7. Telemedicina: Desafios Éticos e Regulatórios

Author

Adriano Marteleto Godinho, Amanda de Meirelles Belliard, Antônio Carlos Efing, Caroline Amadori Cavet, Eduardo Dantas, Fernanda Schaefer, Filipe Medon, Frederico Glitz, Gabriel Schulman, Henrique Manoel Alves, Igor de Lucena Mascarenhas, João Pedro Gebran Neto, José Luiz de Moura Faleiros Júnior, Karin Cristina

Published
2023

8. P863: AN OPEN-LABEL PHASE I/IIA STUDY TO EVALUATE THE SAFETY AND EFFICACY OF CCS1477 AS MONOTHERAPY AND IN COMBINATION WITH POMALIDOMIDE/DEXAMETHASONE IN RELAPSED/REFRACTORY MULTIPLE MYELOMA

Author

Emma Searle, Jim Cavet, Steven Knapper, Ceri Bygrave, Victoria Campbell, Dima El-Sharkawi, Charlotte Pawlyn, Maria Creignou, Harriet S. Walter, David Valcarcel, Marta Hidalgo, Tomasz Knurowski, Karen Clegg, Neil Pegg, Will West, Debbie Haynes, Kris Frese, and Tim C. P. Somervaille

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Published
2023
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10. Chest CT Characteristics are Strongly Predictive of Mortality in Patients with COVID-19 Pneumonia: A Multicentric Cohort Study

Author

Malécot, Nicolas, Chrusciel, Jan, Sanchez, Stéphane, Sellès, Philippe, Goetz, Christophe, Lévêque, Henri-Paul, Parizel, Elizabeth, Pradel, Jean, Almhana, Mouklès, Bouvier, Elodie, Uyttenhove, Fabian, Bonnefoy, Etienne, Vazquez, Guillermo, Adib, Omar, Calvo, Philippe, Antoine, Colette, Jullien, Veronique, Cirille, Sylvia, Dumas, Antoine, Defasque, Anthony, Ben Ghorbal, Yassine, Elkadri, Marwan, Schertz, Mathieu, and Cavet, Madeleine

Published
2022
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11. Limited efficacy of APRIL CAR in patients with multiple myeloma indicate challenges in the use of natural ligands for CAR T-cell therapy

Author

Simon Thomas, Julia Taylor, Manuel Rodriguez-Justo, Kwee Yong, Mathieu Ferrari, Shimobi Onuoha, Sonja Zweegman, Rakesh Popat, Lydia Lee, Wen Chean Lim, Daria Galas-Filipowicz, Kent Fung, Dominic Patel, Zulaikha Akbar, Elena Alvarez Mediavilla, Patrycja Wawrzyniecka, Debarati Shome, Rogier M Reijmers, Trillian Gregg, Leigh Wood, William Day, Virginie Cerec, Shaun Cordoba, Nushmia Khokhar, Vijay Peddareddigari, Muhammad Al-Hajj, Jim Cavet, and Martin Pule

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Background We used a proliferating ligand (APRIL) to construct a ligand-based third generation chimeric antigen receptor (CAR) able to target two myeloma antigens, B-cell maturation antigen (BCMA) and transmembrane activator and CAML interactor.Methods The APRIL CAR was evaluated in a Phase 1 clinical trial (NCT03287804, AUTO2) in patients with relapsed, refractory multiple myeloma. Eleven patients received 13 doses, the first 15×106 CARs, and subsequent patients received 75,225,600 and 900×106 CARs in a 3+3 escalation design.Results The APRIL CAR was well tolerated. Five (45.5%) patients developed Grade 1 cytokine release syndrome and there was no neurotoxicity. However, responses were only observed in 45.5% patients (1×very good partial response, 3×partial response, 1×minimal response). Exploring the mechanistic basis for poor responses, we then compared the APRIL CAR to two other BCMA CARs in a series of in vitro assays, observing reduced interleukin-2 secretion and lack of sustained tumor control by APRIL CAR regardless of transduction method or co-stimulatory domain. There was also impaired interferon signaling of APRIL CAR and no evidence of autoactivation. Thus focusing on APRIL itself, we confirmed similar affinity to BCMA and protein stability in comparison to BCMA CAR binders but reduced binding by cell-expressed APRIL to soluble BCMA and reduced avidity to tumor cells. This indicated either suboptimal folding or stability of membrane-bound APRIL attenuating CAR activation.Conclusions The APRIL CAR was well tolerated, but the clinical responses observed in AUTO2 were disappointing. Subsequently, when comparing the APRIL CAR to other BCMA CARs, we observed in vitro functional deficiencies due to reduced target binding by cell-expressed ligand.

Published
2023
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12. The deficiency in Th2-like Tfh cells affects the maturation and quality of HIV-specific B cell response in viremic infection

Author

Alessandra Noto, Madeleine Suffiotti, Victor Joo, Antonio Mancarella, Francesco A. Procopio, Guy Cavet, Yvonne Leung, Jean-Marc Corpataux, Matthias Cavassini, Agostino Riva, Leonidas Stamatatos, Raphael Gottardo, Adrian B. McDermott, Richard A. Koup, Craig Fenwick, Matthieu Perreau, and Giuseppe Pantaleo

Subjects
lymph nodes, follicular T helper cells, germinal center B cells (GC B cells), HIV-1 infection, T helper cell, Immunologic diseases. Allergy, RC581-607
Abstract

Optimal T follicular helper (Tfh) cells function is important to promote the development of germinal centers and maturation of high affinity antigen-specific B cells. We have found that the expression of CXCR3 defines distinct Tfh subsets: CXCR3+ Th1-like Tfh cells mainly producing single IFN-γ and dual IL-21/IFN-γ and CXCR3- Th2-like Tfh cells mainly producing single IL-4 and dual IL-21/IL-4 cytokines. CXCR3- Th2-like Tfhs are significantly reduced during ongoing HIV replication. While the percentage of Th2-like Tfh cells correlates with that of total and cycling HIV-specific B cells, the percentage of CXCR3+ Th1-like Tfhs correlates with HIV-specific B cells expressing T-bet and CXCR3. Of note, only IL-4 and IL-21 cytokines boosted efficient maturation of HIV-specific B cells while IFN-γ induced expression of T-bet and CXCR3 in B cells. Interestingly, total and HIV-specific CXCR3+ B cells showed lower rate of somatic hypermutation, as compared to CXCR3- B cells. Therefore, the imbalance in Th2/Th1-like Tfhs affects B cell responses in viremic HIV infection.

Published
2022
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14. A candidate antibody drug for prevention of malaria

Author

Williams, Katherine L., primary, Guerrero, Steve, additional, Flores-Garcia, Yevel, additional, Kim, Dongkyoon, additional, Williamson, Kevin S., additional, Siska, Christine, additional, Smidt, Pauline, additional, Jepson, Sofia Z., additional, Li, Kan, additional, Dennison, S. Moses, additional, Mathis-Torres, Shamika, additional, Chen, Xiaomu, additional, Wille-Reece, Ulrike, additional, MacGill, Randall S., additional, Walker, Michael, additional, Jongert, Erik, additional, King, C. Richter, additional, Ockenhouse, Christian, additional, Glanville, Jacob, additional, Moon, James E., additional, Regules, Jason A., additional, Tan, Yann Chong, additional, Cavet, Guy, additional, Lippow, Shaun M., additional, Robinson, William H., additional, Dutta, Sheetij, additional, Tomaras, Georgia D., additional, Zavala, Fidel, additional, Ketchem, Randal R., additional, and Emerling, Daniel E., additional

Published
2024
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15. Bacterial aggregation facilitates internalin-mediated invasion of Listeria monocytogenes.

Author

Feltham, Liam, Moran, Josephine, Goldrick, Marie, Lord, Elizabeth, Spiller, David G., Cavet, Jennifer S., Muldoon, Mark, Roberts, Ian. S., and Paszek, Pawel

Subjects
PROTEIN-tyrosine kinases, LISTERIA monocytogenes, BACTERIAL adhesion, THROMBIN receptors, RNA sequencing, MICROSCOPY
Abstract

Dissemination of food-borne L. monocytogenes in the host relies on internalinmediated invasion, but the underlying invasion strategies remain elusive. Here we use live-cell microscopy to follow single cell interactions between individual human cells and L. monocytogenes and elucidate mechanisms associated with internalin B (InlB)-mediated invasion. We demonstrate that whilst a replicative invasion of nonphagocytic cells is a rare event even at high multiplicities of invasion, L. monocytogenes overcomes this by utilising a strategy relaying on PrfA-mediated ActA-based aggregation. We show that L. monocytogenes forms aggregates in extracellular host cell environment, which promote approximately 5-fold more host cell adhesions than the non-aggregating actA-DC mutant (which lacks the C-terminus coding region), with the adhering bacteria inducing 3-fold more intracellular invasions. Aggregation is associated with robust MET tyrosine kinase receptor clustering in the host cells, a hallmark of InlB-mediated invasion, something not observed with the actA-DC mutant. Finally, we show via RNA-seq analyses that aggregation involves a global adaptive response to host cell environment (including iron depletion), resulting in metabolic changes in L. monocytogenes and upregulation of the PrfA virulence regulon. Overall, our analyses provide new mechanistic insights into internalin-mediated host-pathogen interactions of L. monocytogenes. [ABSTRACT FROM AUTHOR]

Published
2024
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17. P863: AN OPEN-LABEL PHASE I/IIA STUDY TO EVALUATE THE SAFETY AND EFFICACY OF CCS1477 AS MONOTHERAPY AND IN COMBINATION WITH POMALIDOMIDE/DEXAMETHASONE IN RELAPSED/REFRACTORY MULTIPLE MYELOMA

Author

Searle, Emma, primary, Cavet, Jim, additional, Knapper, Steven, additional, Bygrave, Ceri, additional, Campbell, Victoria, additional, El-Sharkawi, Dima, additional, Pawlyn, Charlotte, additional, Creignou, Maria, additional, Walter, Harriet S., additional, Valcarcel, David, additional, Hidalgo, Marta, additional, Knurowski, Tomasz, additional, Clegg, Karen, additional, Pegg, Neil, additional, West, Will, additional, Haynes, Debbie, additional, Frese, Kris, additional, and Somervaille, Tim C. P., additional

Published
2023
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18. Fragment correlation mass spectrometry: Determining the structures of biopolymers in a complex mixture without isolating individual components.

Author

Yangjie Li, Cavet, Guy, Zare, Richard N., and Driver, Taran

Subjects
*TANDEM mass spectrometry, *ION traps, *ION pairs, *MASS spectrometry, *BIOPOLYMERS
Abstract

Fragment correlation mass spectrometry correlates ion pairs generated from the same fragmentation pathway, achieved by covariance mapping of tandem mass spectra generated with an unmodified linear ion trap without preseparation. We enable the identification of different precursors at different charge states in a complex mixture from a large isolation window, empowering an analytical approach for data-independent acquisition. The method resolves and matches isobaric fragments, internal ions, and disulfide bond fragments. We suggest that this method represents a major advance for analyzing structures of biopolymers in mixtures. [ABSTRACT FROM AUTHOR]

Published
2024
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21. Limited efficacy of APRIL CAR in patients with multiple myeloma indicate challenges in the use of natural ligands for CAR T-cell therapy

Author

Lee, Lydia, primary, Lim, Wen Chean, additional, Galas-Filipowicz, Daria, additional, Fung, Kent, additional, Taylor, Julia, additional, Patel, Dominic, additional, Akbar, Zulaikha, additional, Alvarez Mediavilla, Elena, additional, Wawrzyniecka, Patrycja, additional, Shome, Debarati, additional, Reijmers, Rogier M, additional, Gregg, Trillian, additional, Wood, Leigh, additional, Day, William, additional, Cerec, Virginie, additional, Ferrari, Mathieu, additional, Thomas, Simon, additional, Cordoba, Shaun, additional, Onuoha, Shimobi, additional, Khokhar, Nushmia, additional, Peddareddigari, Vijay, additional, Al-Hajj, Muhammad, additional, Cavet, Jim, additional, Zweegman, Sonja, additional, Rodriguez-Justo, Manuel, additional, Yong, Kwee, additional, Pule, Martin, additional, and Popat, Rakesh, additional

Published
2023
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22. An antibody drug engineered for prevention of malaria in global populations

Author

Emerling, Daniel, primary, Williams, Katherine, additional, Guerrero, Steve, additional, Flores-Garcia, Yevel, additional, Andrews, Kayla, additional, Kim, Dongkyoon, additional, Williamson, Kevin, additional, Siska, Christine, additional, Smidt, Pauline, additional, Jepson, Sofia, additional, Liu, Hong, additional, Li, Kan, additional, Dennison, S, additional, Mathis-Torres, Shamika, additional, Chen, Xiaomu, additional, Wille-Reece, Ulrike, additional, MacGill, Randall, additional, Walker, Michael, additional, Jongert, Erik, additional, King, C, additional, Ockenhouse, Christian, additional, Glanville, Jacob, additional, Moon, James, additional, Regules, Jason, additional, Tan, Yann Chong, additional, Cavet, Guy, additional, Lippow, Shaun, additional, Robinson, William, additional, Dutta, Sheetij, additional, Tomaras, Georgia, additional, Zavala, Fidel, additional, and Ketchem, Randal, additional

Published
2023
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23. Supplementary Table S1 from Genetic Alterations and Oncogenic Pathways Associated with Breast Cancer Subtypes

Author

Hu, Xiaolan, primary, Stern, Howard M., primary, Ge, Lin, primary, O'Brien, Carol, primary, Haydu, Lauren, primary, Honchell, Cynthia D., primary, Haverty, Peter M., primary, Peters, Brock A., primary, Wu, Thomas D., primary, Amler, Lukas C., primary, Chant, John, primary, Stokoe, David, primary, Lackner, Mark R., primary, and Cavet, Guy, primary

Published
2023
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25. Supplementary Data from Oncogenic Activating Mutations Are Associated with Local Copy Gain

Author

Modrek, Barmak, primary, Ge, Lin, primary, Pandita, Ajay, primary, Lin, Eva, primary, Mohan, Sankar, primary, Yue, Peng, primary, Guerrero, Steve, primary, Lin, William M., primary, Pham, Thinh, primary, Modrusan, Zora, primary, Seshagiri, Somasekar, primary, Stern, Howard M., primary, Waring, Paul, primary, Garraway, Levi A., primary, Chant, John, primary, Stokoe, David, primary, and Cavet, Guy, primary

Published
2023
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26. Supplementary Figures S1-S4 from Genetic Alterations and Oncogenic Pathways Associated with Breast Cancer Subtypes

Author

Hu, Xiaolan, primary, Stern, Howard M., primary, Ge, Lin, primary, O'Brien, Carol, primary, Haydu, Lauren, primary, Honchell, Cynthia D., primary, Haverty, Peter M., primary, Peters, Brock A., primary, Wu, Thomas D., primary, Amler, Lukas C., primary, Chant, John, primary, Stokoe, David, primary, Lackner, Mark R., primary, and Cavet, Guy, primary

Published
2023
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27. SUSTENTABILIDADE NAS UNIVERSIDADES: INTERESSES, CRÍTICAS E PREOCUPAÇÕES DA COMUNIDADE ACADÊMICA SOBRE ATITUDES SUSTENTÁVEIS ALICERÇADO AO UI GREENMETRIC

Author

Cavet, Guilherme Rodrigues, Lago, Sandra Mara Stocker, Johann, Jerry Adriani, and Bertolini, Geysler Rogis Flor

Subjects
RSU, Ranking GM, Universidades Sustentáveis, Comunidade Acadêmica
Abstract

Um dos modos de medir o quanto uma universidade é sustentável, é por meio do UI GreenMetric (GM) Ranking, que realiza uma análise dos três pilares da sustentabilidade, por meio de seis categorias avaliadas: infraestrutura e meio ambiente; energia; resíduos; água; transporte; e educação. Neste estudo se objetiva analisar as preocupações e interesses da comunidade acadêmica, fundamentado pelo GM Ranking, sobre as práticas sustentáveis do Campus. Foram realizadas análises sobre quatro variáveis: gênero, vínculo com a instituição, acadêmicos que cursam ou não disciplinas sobre sustentabilidade e faixa etária, os resultados indicam que não houve diferenças significativas entre diferenças de sexo e de vínculos com a universidade, porém acadêmicos que cursam disciplinas sobre sustentabilidade tem mais interesse sobre o tema, e os mais jovens, além do interesse, se mostram mais preocupados com o assunto. Conclui-se que há uma demanda por cursos, treinamentos e disciplinas curriculares sobre sustentabilidade por parte da comunidade acadêmica, e que os mais jovens são mais críticos e preocupados com as atitudes sustentáveis do campus.

Published
2023

28. An antibody drug engineered for prevention of malaria in global populations

Author

Katherine Williams, Steve Guerrero, Yevel Flores-Garcia, Kayla Andrews, Dongkyoon Kim, Kevin Williamson, Christine Siska, Pauline Smidt, Sofia Jepson, Hong Liu, Kan Li, S Dennison, Shamika Mathis-Torres, Xiaomu Chen, Ulrike Wille-Reece, Randall MacGill, Michael Walker, Erik Jongert, C King, Christian Ockenhouse, Jacob Glanville, James Moon, Jason Regules, Yann Chong Tan, Guy Cavet, Shaun Lippow, William Robinson, Sheetij Dutta, Georgia Tomaras, Fidel Zavala, Randal Ketchem, and Daniel Emerling

Abstract

Over 80% of malaria-attributable deaths are in children under five. However, the only malaria vaccine recommended by the World Health Organization (WHO) for paediatric use, Mosquirix™, has limited efficacy. Complementary strategies, like monoclonal antibodies (mAbs), will be required to eradicate malaria. To discover new anti-malaria mAbs, we evaluated >28,000 antibody sequences from circulating B cells obtained from 45 Mosquirix™ vaccinees and selected 369 for testing. Many antibodies bound the circumsporozoite protein (CSP), a main surface protein on malaria and the malaria antigen in Mosquirix™, and several were exceptionally protective in mouse models of malaria. Through this work, we identified surprising correlations that suggest certain CSP sequences in Mosquirix™ may induce immunodominant antibody responses that dilute protective immunity. Further, we selected the antibodies most protective in preclinical mouse models and engineered them for improved manufacturability and developability to meet WHO guidelines. An optimised clinical candidate, MAM01, suitable for paediatric populations living in low-to-middle-income countries, was selected for clinical development.

Published
2023
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31. Supplementary Figures S1-S4 from Genetic Alterations and Oncogenic Pathways Associated with Breast Cancer Subtypes

Author

Guy Cavet, Mark R. Lackner, David Stokoe, John Chant, Lukas C. Amler, Thomas D. Wu, Brock A. Peters, Peter M. Haverty, Cynthia D. Honchell, Lauren Haydu, Carol O'Brien, Lin Ge, Howard M. Stern, and Xiaolan Hu

Abstract

Supplementary Figures S1-S4 from Genetic Alterations and Oncogenic Pathways Associated with Breast Cancer Subtypes

Published
2023
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32. Data from Oncogenic Activating Mutations Are Associated with Local Copy Gain

Author

Guy Cavet, David Stokoe, John Chant, Levi A. Garraway, Paul Waring, Howard M. Stern, Somasekar Seshagiri, Zora Modrusan, Thinh Pham, William M. Lin, Steve Guerrero, Peng Yue, Sankar Mohan, Eva Lin, Ajay Pandita, Lin Ge, and Barmak Modrek

Abstract

Although activating mutations and gains in copy number are key mechanisms for oncogene activation, the relationship between the two is not well understood. In this study, we focused on KRAS copy gains and mutations in non–small cell lung cancer. We found that KRAS copy gains occur more frequently in tumors with KRAS activating mutations and are associated with large increases in KRAS expression. These copy gains tend to be more focal in tumors with activating mutations than in those with wild-type KRAS. Fluorescence in situ hybridization analysis revealed that some tumors have homogeneous low-level gains of the KRAS locus, whereas others have high-level amplification of KRAS, often in only a fraction of tumor cells. Associations between activating mutation and copy gains were also observed for other oncogenes (EGFR in non–small cell lung cancer, BRAF and NRAS in melanoma). Activating mutations were associated with copy gains only at the mutated oncogene locus but not other oncogene loci. However, KRAS activating mutations in colorectal cancer were not associated with copy gains. Future work is warranted to clarify the relationship among the different mechanisms of oncogene activation. (Mol Cancer Res 2009;7(8):1244–52)

Published
2023
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33. Commentary on this Article from Molecular predictors of response to a humanized anti–insulin-like growth factor-I receptor monoclonal antibody in breast and colorectal cancer

Author

Mark R. Lackner, Lukas C. Amler, Xiaolan Hu, Guy Cavet, Elizabeth Luis, Gail D. Lewis Phillips, Leanne Berry, Fiona Zhong, Ling-Yuh Huw, Heidi Savage, Carol O'Brien, and Jiping Zha

Abstract

Commentary on this Article from Molecular predictors of response to a humanized anti–insulin-like growth factor-I receptor monoclonal antibody in breast and colorectal cancer

Published
2023
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34. Data from Molecular predictors of response to a humanized anti–insulin-like growth factor-I receptor monoclonal antibody in breast and colorectal cancer

Author

Mark R. Lackner, Lukas C. Amler, Xiaolan Hu, Guy Cavet, Elizabeth Luis, Gail D. Lewis Phillips, Leanne Berry, Fiona Zhong, Ling-Yuh Huw, Heidi Savage, Carol O'Brien, and Jiping Zha

Abstract

The insulin-like growth factor-I receptor (IGF-IR) pathway is required for the maintenance of the transformed phenotype in neoplastic cells and hence has been the subject of intensive drug discovery efforts. A key aspect of successful clinical development of targeted therapies directed against IGF-IR will be identification of responsive patient populations. Toward that end, we have endeavored to identify predictive biomarkers of response to an anti-IGF-IR-targeting monoclonal antibody in preclinical models of breast and colorectal cancer. We find that levels of the IGF-IR itself may have predictive value in these tumor types and identify other gene expression predictors of in vitro response. Studies in breast cancer models suggest that IGF-IR expression is both correlated and functionally linked with estrogen receptor signaling and provide a basis for both patient stratification and rational combination therapy with antiestrogen-targeting agents. In addition, we find that levels of other components of the signaling pathway such as the adaptor proteins IRS1 and IRS2, as well as the ligand IGF-II, have predictive value and report on the development of a pathway-focused panel of diagnostic biomarkers that could be used to test these hypotheses during clinical development of IGF-IR-targeting therapies. [Mol Cancer Ther 2009;8(8):2110–21]

Published
2023
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35. Supplementary Figures 1-7 from Molecular predictors of response to a humanized anti–insulin-like growth factor-I receptor monoclonal antibody in breast and colorectal cancer

Author

Mark R. Lackner, Lukas C. Amler, Xiaolan Hu, Guy Cavet, Elizabeth Luis, Gail D. Lewis Phillips, Leanne Berry, Fiona Zhong, Ling-Yuh Huw, Heidi Savage, Carol O'Brien, and Jiping Zha

Abstract

Supplementary Figures 1-7 from Molecular predictors of response to a humanized anti–insulin-like growth factor-I receptor monoclonal antibody in breast and colorectal cancer

Published
2023
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36. Data from In vivo Antitumor Activity of MEK and Phosphatidylinositol 3-Kinase Inhibitors in Basal-Like Breast Cancer Models

Author

Mark R. Lackner, Lori S. Friedman, Marcia Belvin, Lukas Amler, Lesley Murray, Leanne Berry, Wei Zhou, Tom Truong, Elizabeth Punnoose, Heidi Savage, Tom Januario, Kenneth Jung, Steve Guerrero, Guy Cavet, Zachary Boyd, Carol O'Brien, and Klaus P. Hoeflich

Abstract

Purpose: The pathways underlying basal-like breast cancer are poorly understood, and as yet, there is no approved targeted therapy for this disease. We investigated the role of mitogen-activated protein kinase kinase (MEK) and phosphatidylinositol 3-kinase (PI3K) inhibitors as targeted therapies for basal-like breast cancer.Experimental Design: We used pharmacogenomic analysis of a large panel of breast cancer cell lines with detailed accompanying molecular information to identify molecular predictors of response to a potent and selective inhibitor of MEK and also to define molecular mechanisms underlying combined MEK and PI3K targeting in basal-like breast cancer. Hypotheses were confirmed by testing in multiple tumor xenograft models.Results: We found that basal-like breast cancer models have an activated RAS-like transcriptional program and show greater sensitivity to a selective inhibitor of MEK compared with models representative of other breast cancer subtypes. We also showed that loss of PTEN is a negative predictor of response to MEK inhibition, that treatment with a selective MEK inhibitor caused up-regulation of PI3K pathway signaling, and that dual blockade of both PI3K and MEK/extracellular signal–regulated kinase signaling synergized to potently impair the growth of basal-like breast cancer models in vitro and in vivo.Conclusions: Our studies suggest that single-agent MEK inhibition is a promising therapeutic modality for basal-like breast cancers with intact PTEN, and also provide a basis for rational combination of MEK and PI3K inhibitors in basal-like cancers with both intact and deleted PTEN.

Published
2023
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37. Supplementary Data from In vivo Antitumor Activity of MEK and Phosphatidylinositol 3-Kinase Inhibitors in Basal-Like Breast Cancer Models

Author

Mark R. Lackner, Lori S. Friedman, Marcia Belvin, Lukas Amler, Lesley Murray, Leanne Berry, Wei Zhou, Tom Truong, Elizabeth Punnoose, Heidi Savage, Tom Januario, Kenneth Jung, Steve Guerrero, Guy Cavet, Zachary Boyd, Carol O'Brien, and Klaus P. Hoeflich

Abstract

Supplementary Data from In vivo Antitumor Activity of MEK and Phosphatidylinositol 3-Kinase Inhibitors in Basal-Like Breast Cancer Models

Published
2023
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41. Data from Functional Genomics Identifies ABCC3 as a Mediator of Taxane Resistance in HER2-Amplified Breast Cancer

Author

Mark R. Lackner, Lukas C. Amler, Zora Modrusan, Celina Sanchez Rivers, Karen Toy, Sankar Mohan, Lauren Haydu, Xiaolan Hu, Ajay Pandita, Guy Cavet, and Carol O'Brien

Abstract

Breast cancer is a heterogeneous disease with distinct molecular subtypes characterized by differential response to targeted and chemotherapeutic agents. Enhanced understanding of the genetic alterations characteristic of different subtypes is needed to pave the way for more personalized administration of therapeutic agents. We have taken a functional genomics approach using a well-characterized panel of breast cancer cell lines to identify putative biomarkers of resistance to antimitotic agents such as paclitaxel and monomethyl-auristatin-E (MMAE). In vitro studies revealed a striking difference in sensitivity to these agents between cell lines from different subtypes, with basal-like cell lines being significantly more sensitive to both agents than luminal or HER2-amplified cell lines. Genome-wide association studies using copy number data from Affymetrix single nucleotide polymorphism arrays identified amplification of the chromosome 17q21 region as being highly associated with resistance to both paclitaxel and MMAE. An unbiased approach consisting of RNA interference and high content analysis was used to show that amplification and concomitant overexpression of the gene encoding the ABCC3 drug transporter is responsible for conferring in vitro resistance to paclitaxel and MMAE. We also show that amplification of ABCC3 is present in primary breast tumors and that it occurs predominantly in HER2-amplified and luminal tumors, and we report on development of a specific fluorescence in situ hybridization assay that may have utility as a predictive biomarker of taxane resistance in breast cancer. [Cancer Res 2008;68(13):5380–9]

Published
2023
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43. Supplementary Figure Legends 1-5 from Functional Genomics Identifies ABCC3 as a Mediator of Taxane Resistance in HER2-Amplified Breast Cancer

Author

Mark R. Lackner, Lukas C. Amler, Zora Modrusan, Celina Sanchez Rivers, Karen Toy, Sankar Mohan, Lauren Haydu, Xiaolan Hu, Ajay Pandita, Guy Cavet, and Carol O'Brien

Abstract

Supplementary Figure Legends 1-5 from Functional Genomics Identifies ABCC3 as a Mediator of Taxane Resistance in HER2-Amplified Breast Cancer

Published
2023
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48. How a European network of FAIR-enabling Trustworthy Data Repositories can align to the vision of EOSC

Author

Anglada, Lluís, Antos, David, Burgi, Pierre-Yves, Cavet, Cécile, Celjak, Draženko, Dillo, Ingrid, Dubois, Olesea, Fernandes, Rui, Lamers, Didi, L'Hours, Hervé, Venkataraman, Shanmugasundaram, Viljoen, Matthew, Wyns, Roxanne, L'Hours, Hervé, and Wyns, Roxanne

Subjects
EOSC, HorizonEU, EOSC Association, Advancing OpenScience in Europe, Long term data preservation, EOSC Association Long Term Data Preservation Task Force, OpenScience, Trustworthy Digital Repositories, FAIR, Response paper
Abstract

This paper is a response from the EOSC Association Long Term Data Preservation Task Force to the working paper “Toward a European network of FAIR-enabling Trustworthy Digital Repositories”. In this response the EOSC LTDP Task Force addresses the proposals in the paper and elaborates on how the suggested functions can contribute to realising the EOSC.

Published
2023
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49. EOSC Preservation: Overview Discussion Paper

Author

Andreu, Toni, Anglada, Lluís, Antos, David, Bähr, Thomas, Brzeźniak, Maciej, Burgi, Pierre-Yves, Cavet, Cécile, Celjak, Draženko, Crépé-Renaudin, Sabine, De Loof, Chris, Dillo, Ingrid, Dubois, Olesea, Fernandes, Rui, Forsström, Pirjo-Leena, Ganis, Gerardo, Gibney, Eileen, Holl, András, L'Hours, Hervé, Lamers, Didi, Lammert, Andrea, Lloret Iglesias, Lara, Maggi, Marcello, Majdanski, Mariusz, Nief, Jean-Yves, Novacek, Jiri, Piroi, Florina, Presser, Karl, Saenen, Bregt, Shankar, Sangeetha, Smareglia, Riccardo, Stockhause, Martina, Stokes, Paul, Tenhunen, Ville, Venkataraman, Shanmugasundaram, Viljoen, Matthew, Wali, Mojib, Wyns, Roxanne, Hervé L'Hours, and Roxanne Wyns

Subjects
EOSC, HorizonEU, EOSC Association, Advancing OpenScience in Europe, EOSC Association Long Term Data Preservation Task force, Long term data preservation, OpenScience, Trustworthy Digital Repositories, FAIR, Overview Discussion Paper
Abstract

TheLong-Term Data Preservation Task Force(LTDP TF) of the EOSC Association has since its establishment worked on mapping the status and further clarification of the meaning of long-term preservation within the EOSC. This work has resulted in anoverview and discussion paperto presents the context, activities and ongoing issues surrounding the EOSC Association Long Term Data Preservation Task Force. The paper describes our approach on preservation in the context of EOSC concerning outcomes, systems, and actions with attention to the vision, roles, finance, and networks needed to deliver preservation for FAIR digital objects in the EOSC. This document is intended to collect community feedback on our approach as well as future recommendations to be considered. We kindly ask the community for feedback on our approach as well as future recommendations to be considered through a short survey: https://ec.europa.eu/eusurvey/runner/TFLTDPsurvey2023

Published
2023
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50. CCR Translation for the Article from In vivo Antitumor Activity of MEK and Phosphatidylinositol 3-Kinase Inhibitors in Basal-Like Breast Cancer Models

Author

Hoeflich, Klaus P., primary, O'Brien, Carol, primary, Boyd, Zachary, primary, Cavet, Guy, primary, Guerrero, Steve, primary, Jung, Kenneth, primary, Januario, Tom, primary, Savage, Heidi, primary, Punnoose, Elizabeth, primary, Truong, Tom, primary, Zhou, Wei, primary, Berry, Leanne, primary, Murray, Lesley, primary, Amler, Lukas, primary, Belvin, Marcia, primary, Friedman, Lori S., primary, and Lackner, Mark R., primary

Published
2023
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