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Browsing by Author "Rodrigues, S."

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    ItemOpen Access
    Blocking PI3K p110β attenuates development of PTEN-deficient castration-resistant prostate cancer
    (American Association for Cancer Research, 2022-01-26) Gao, X.; Wang, Y.; Ribeiro, C. F.; Manokaran, C.; Chang, H.; Von, T.; Rodrigues, S.; Çizmecioğlu, Onur; Jia, S.; Korpal, M.; Korn, J. M.; Wang, Z.; Schmit, F.; Jiang, L.; Pagliarini, R.; Yang, Y.; Sethi, I.; Signoretti, S.; Yuan, G.; Loda, M.; Zhao, J. J.; Roberts, T. M.
    A common outcome of androgen deprivation in prostate cancer therapy is disease relapse and progression to castration-resistant prostate cancer (CRPC) via multiple mechanisms. To gain insight into the recent clinical findings that highlighted genomic alterations leading to hyperactivation of PI3K, we examined the roles of the commonly expressed p110 catalytic isoforms of PI3K in a murine model of Pten-null invasive CRPC. While blocking p110α had negligible effects in the development of Pten-null invasive CRPC, either genetic or pharmacologic perturbation of p110β dramatically slowed CRPC initiation and progression. Once fully established, CRPC tumors became partially resistant to p110β inhibition, indicating the acquisition of new dependencies. Driven by our genomic analyses highlighting potential roles for the p110β/RAC/PAK1 and β-catenin pathways in CRPC, we found that combining p110β with RAC/PAK1 or tankyrase inhibitors significantly reduced the growth of murine and human CRPC organoids in vitro and in vivo. Because p110β activity is dispensable for most physiologic processes, our studies support novel therapeutic strategies both for preventing disease progression into CRPC and for treating CRPC.
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    Building bridges through science
    (Elsevier (Cell Press), 2017-11) Lissek, T.; Adams, M.; Adelman, J.; Ahissar, E.; Akaaboune, M.; Akil, H.; al’Absi, M.; Arain, F.; Arango-Lasprilla, J. C.; Atasoy, D.; Avila, J.; Badawi, A.; Bading, H.; Mannan Baig, A.; Baleriola, J.; Belmonte, C.; Bertocchi, I.; Betz, H.; Blakemore, C.; Blanke, O.; Boehm-Sturm, P.; Bonhoeffer, T.; Bonifazi, P.; Brose, N.; Campolongo, P.; Celikel, T.; C. Chang, C.; Chang, T.; Citri, A.; Cline, H. T.; Cortes, J. M.; Cullen, K.; Dean, K.; Delgado-Garcia, J. M.; Desroches, M.; Disterhoft, J. F.; Dowling, J. E.; Draguhn, A.; El-Khamisy, S. F.; El Manira, A.; Enam, S. A.; Encinas, J. M.; Erramuzpe, A.; Esteban, J. A.; Fariñas, I.; Fischer, E.; Fukunaga, I.; Gabilondo, I.; Ganten, D.; Gidon, A.; Gomez-Esteban, J. C.; Greengard, P.; Grinevich, V.; Gruart, A.; Guillemin, R.; Hariri, A. R.; Hassan, B.; Häusser, M.; Hayashi, Y.; K. Hussain, N.; Jabbar, A. A.; Jaber, M.; Jahn, R.; Janahi, E. M.; Kabbaj, M.; Kettenmann, H.; Kindt, M.; Knafo, S.; Köhr, G.; Komai, S.; Krugers, H.; Kuhn, B.; Ghazal, N. L.; Larkum, M. E.; London, M.; Lutz, B.; Matute, C.; Martinez-Millan, L.; Maroun, M.; McGaugh, J.; Moustafa, A. A.; Nasim, A.; Nave, K. A.; Neher, E.; Nikolich, K.; Outeiro, T.; Palmer, L. M.; Penagarikano, O.; Perez-Otano, I.; Pfaff, D. W.; Poucet, B.; Rahman, A.; Ramos-Cabrer, P.; Rashidy-Pour, A.; Roberts, R. J.; Rodrigues, S.; Sanes, J. R.; Schaefer, A. T.; Segal, M.; Segev, I.; Shafqat, S.; Siddiqui, N. A.; Soreq, H.; Soriano-García, E.; Spanagel, R.; Sprengel, R.; Stuart, G.; Südhof, T. C.; Tønnesen, J.; Treviño, M.; Uthman, B. M.; Venter, J. C.; Verkhratsky, A.; Weiss, C.; Wiesel, T. N.; Yaksi, E.; Yizhar, O.; Young, L. J.; Young, Y.; Zawia, N. H.; Zugaza, J. L.; Hasan, M. T.
    Science is ideally suited to connect people from different cultures and thereby foster mutual understanding. To promote international life science collaboration, we have launched “The Science Bridge” initiative. Our current project focuses on partnership between Western and Middle Eastern neuroscience communities.

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