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10 results on '"Maya K. Gelbard"'

1. Supplementary Table S5 from Pooled Genomic Screens Identify Anti-apoptotic Genes as Targetable Mediators of Chemotherapy Resistance in Ovarian Cancer

Author

Matthew Meyerson, Cory M. Johannessen, Levi A. Garraway, Anthony Letai, Kristopher A. Sarosiek, David D.L. Bowtell, Ursula A. Matulonis, Federica Piccioni, Andrew D. Cherniack, Felice J. Liang, Joan Montero, Jennifer L. Guerriero, Jeremy Ryan, Patrick D. Bhola, Ioannis K. Zervantonakis, Weiqun Zhang, Maya K. Gelbard, Adam G. Presser, Guo Wei, Matthew G. Rees, Sasha Pantel, Yenarae Lee, Amy Goodale, Mukta Bagul, Elizabeth L. Christie, Yvonne Y. Li, Ofir Cohen, Maria B. Baco, and Elizabeth H. Stover

Abstract

CRISPR-Cas9 screen data

Published
2023
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2. Data from Pooled Genomic Screens Identify Anti-apoptotic Genes as Targetable Mediators of Chemotherapy Resistance in Ovarian Cancer

Author

Matthew Meyerson, Cory M. Johannessen, Levi A. Garraway, Anthony Letai, Kristopher A. Sarosiek, David D.L. Bowtell, Ursula A. Matulonis, Federica Piccioni, Andrew D. Cherniack, Felice J. Liang, Joan Montero, Jennifer L. Guerriero, Jeremy Ryan, Patrick D. Bhola, Ioannis K. Zervantonakis, Weiqun Zhang, Maya K. Gelbard, Adam G. Presser, Guo Wei, Matthew G. Rees, Sasha Pantel, Yenarae Lee, Amy Goodale, Mukta Bagul, Elizabeth L. Christie, Yvonne Y. Li, Ofir Cohen, Maria B. Baco, and Elizabeth H. Stover

Abstract

High-grade serous ovarian cancer (HGSOC) is often sensitive to initial treatment with platinum and taxane combination chemotherapy, but most patients relapse with chemotherapy-resistant disease. To systematically identify genes modulating chemotherapy response, we performed pooled functional genomic screens in HGSOC cell lines treated with cisplatin, paclitaxel, or cisplatin plus paclitaxel. Genes in the intrinsic pathway of apoptosis were among the top candidate resistance genes in both gain-of-function and loss-of-function screens. In an open reading frame overexpression screen, followed by a mini-pool secondary screen, anti-apoptotic genes including BCL2L1 (BCL-XL) and BCL2L2 (BCL-W) were associated with chemotherapy resistance. In a CRISPR-Cas9 knockout screen, loss of BCL2L1 decreased cell survival whereas loss of proapoptotic genes promoted resistance. To dissect the role of individual anti-apoptotic proteins in HGSOC chemotherapy response, we evaluated overexpression or inhibition of BCL-2, BCL-XL, BCL-W, and MCL1 in HGSOC cell lines. Overexpression of anti-apoptotic proteins decreased apoptosis and modestly increased cell viability upon cisplatin or paclitaxel treatment. Conversely, specific inhibitors of BCL-XL, MCL1, or BCL-XL/BCL-2, but not BCL-2 alone, enhanced cell death when combined with cisplatin or paclitaxel. Anti-apoptotic protein inhibitors also sensitized HGSOC cells to the poly (ADP-ribose) polymerase inhibitor olaparib. These unbiased screens highlight anti-apoptotic proteins as mediators of chemotherapy resistance in HGSOC, and support inhibition of BCL-XL and MCL1, alone or combined with chemotherapy or targeted agents, in treatment of primary and recurrent HGSOC.Implications:Anti-apoptotic proteins modulate drug resistance in ovarian cancer, and inhibitors of BCL-XL or MCL1 promote cell death in combination with chemotherapy.

Published
2023
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3. Supplementary Table S1 from Pooled Genomic Screens Identify Anti-apoptotic Genes as Targetable Mediators of Chemotherapy Resistance in Ovarian Cancer

Author

Matthew Meyerson, Cory M. Johannessen, Levi A. Garraway, Anthony Letai, Kristopher A. Sarosiek, David D.L. Bowtell, Ursula A. Matulonis, Federica Piccioni, Andrew D. Cherniack, Felice J. Liang, Joan Montero, Jennifer L. Guerriero, Jeremy Ryan, Patrick D. Bhola, Ioannis K. Zervantonakis, Weiqun Zhang, Maya K. Gelbard, Adam G. Presser, Guo Wei, Matthew G. Rees, Sasha Pantel, Yenarae Lee, Amy Goodale, Mukta Bagul, Elizabeth L. Christie, Yvonne Y. Li, Ofir Cohen, Maria B. Baco, and Elizabeth H. Stover

Abstract

ORF overexpression screen data

Published
2023
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4. Supplementary methods from Pooled Genomic Screens Identify Anti-apoptotic Genes as Targetable Mediators of Chemotherapy Resistance in Ovarian Cancer

Author

Matthew Meyerson, Cory M. Johannessen, Levi A. Garraway, Anthony Letai, Kristopher A. Sarosiek, David D.L. Bowtell, Ursula A. Matulonis, Federica Piccioni, Andrew D. Cherniack, Felice J. Liang, Joan Montero, Jennifer L. Guerriero, Jeremy Ryan, Patrick D. Bhola, Ioannis K. Zervantonakis, Weiqun Zhang, Maya K. Gelbard, Adam G. Presser, Guo Wei, Matthew G. Rees, Sasha Pantel, Yenarae Lee, Amy Goodale, Mukta Bagul, Elizabeth L. Christie, Yvonne Y. Li, Ofir Cohen, Maria B. Baco, and Elizabeth H. Stover

Abstract

Supplementary detailed methods

Published
2023
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5. Supplementary Table S4 from Pooled Genomic Screens Identify Anti-apoptotic Genes as Targetable Mediators of Chemotherapy Resistance in Ovarian Cancer

Author

Matthew Meyerson, Cory M. Johannessen, Levi A. Garraway, Anthony Letai, Kristopher A. Sarosiek, David D.L. Bowtell, Ursula A. Matulonis, Federica Piccioni, Andrew D. Cherniack, Felice J. Liang, Joan Montero, Jennifer L. Guerriero, Jeremy Ryan, Patrick D. Bhola, Ioannis K. Zervantonakis, Weiqun Zhang, Maya K. Gelbard, Adam G. Presser, Guo Wei, Matthew G. Rees, Sasha Pantel, Yenarae Lee, Amy Goodale, Mukta Bagul, Elizabeth L. Christie, Yvonne Y. Li, Ofir Cohen, Maria B. Baco, and Elizabeth H. Stover

Abstract

Secondary mini-pool overexpression screen data

Published
2023
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6. Supplementary Table S3 from Pooled Genomic Screens Identify Anti-apoptotic Genes as Targetable Mediators of Chemotherapy Resistance in Ovarian Cancer

Author

Matthew Meyerson, Cory M. Johannessen, Levi A. Garraway, Anthony Letai, Kristopher A. Sarosiek, David D.L. Bowtell, Ursula A. Matulonis, Federica Piccioni, Andrew D. Cherniack, Felice J. Liang, Joan Montero, Jennifer L. Guerriero, Jeremy Ryan, Patrick D. Bhola, Ioannis K. Zervantonakis, Weiqun Zhang, Maya K. Gelbard, Adam G. Presser, Guo Wei, Matthew G. Rees, Sasha Pantel, Yenarae Lee, Amy Goodale, Mukta Bagul, Elizabeth L. Christie, Yvonne Y. Li, Ofir Cohen, Maria B. Baco, and Elizabeth H. Stover

Abstract

ORF constructs in secondary mini-pool overexpression screen

Published
2023
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7. Supplementary Table S2 from Pooled Genomic Screens Identify Anti-apoptotic Genes as Targetable Mediators of Chemotherapy Resistance in Ovarian Cancer

Author

Matthew Meyerson, Cory M. Johannessen, Levi A. Garraway, Anthony Letai, Kristopher A. Sarosiek, David D.L. Bowtell, Ursula A. Matulonis, Federica Piccioni, Andrew D. Cherniack, Felice J. Liang, Joan Montero, Jennifer L. Guerriero, Jeremy Ryan, Patrick D. Bhola, Ioannis K. Zervantonakis, Weiqun Zhang, Maya K. Gelbard, Adam G. Presser, Guo Wei, Matthew G. Rees, Sasha Pantel, Yenarae Lee, Amy Goodale, Mukta Bagul, Elizabeth L. Christie, Yvonne Y. Li, Ofir Cohen, Maria B. Baco, and Elizabeth H. Stover

Abstract

ORF overexpression screen enrichment analysis

Published
2023
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8. Supplementary Table S6 from Pooled Genomic Screens Identify Anti-apoptotic Genes as Targetable Mediators of Chemotherapy Resistance in Ovarian Cancer

Author

Matthew Meyerson, Cory M. Johannessen, Levi A. Garraway, Anthony Letai, Kristopher A. Sarosiek, David D.L. Bowtell, Ursula A. Matulonis, Federica Piccioni, Andrew D. Cherniack, Felice J. Liang, Joan Montero, Jennifer L. Guerriero, Jeremy Ryan, Patrick D. Bhola, Ioannis K. Zervantonakis, Weiqun Zhang, Maya K. Gelbard, Adam G. Presser, Guo Wei, Matthew G. Rees, Sasha Pantel, Yenarae Lee, Amy Goodale, Mukta Bagul, Elizabeth L. Christie, Yvonne Y. Li, Ofir Cohen, Maria B. Baco, and Elizabeth H. Stover

Abstract

CRISPR-Cas9 screen enrichment analysis

Published
2023
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9. Data from Genetic Ancestry Contributes to Somatic Mutations in Lung Cancers from Admixed Latin American Populations

Author

Matthew Meyerson, Alexander Gusev, Andres F. Cardona, Oscar Arrieta, Geoffrey R. Oxnard, Joshua D. Campbell, Gavin Ha, Yoichiro Mitsuishi, Luis Corrales-Rodriguez, Maya K. Gelbard, July Rodriguez, Giulio Genovese, Jacqueline Watson, Anwesha Nag, Aaron R. Thorner, Nick Patterson, Giovanny Soca-Chafre, and Jian Carrot-Zhang

Abstract

Inherited lung cancer risk, particularly in nonsmokers, is poorly understood. Genomic and ancestry analysis of 1,153 lung cancers from Latin America revealed striking associations between Native American ancestry and their somatic landscape, including tumor mutational burden, and specific driver mutations in EGFR, KRAS, and STK11. A local Native American ancestry risk score was more strongly correlated with EGFR mutation frequency compared with global ancestry correlation, suggesting that germline genetics (rather than environmental exposure) underlie these disparities.Significance:The frequency of somatic EGFR and KRAS mutations in lung cancer varies by ethnicity, but we do not understand why. Our study suggests that the variation in EGFR and KRAS mutation frequency is associated with genetic ancestry and suggests further studies to identify germline alleles that underpin this association.See related commentary by Gomez et al., p. 534.This article is highlighted in the In This Issue feature, p. 521

Published
2023
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10. Supplementary Data from Genetic Ancestry Contributes to Somatic Mutations in Lung Cancers from Admixed Latin American Populations

Author

Matthew Meyerson, Alexander Gusev, Andres F. Cardona, Oscar Arrieta, Geoffrey R. Oxnard, Joshua D. Campbell, Gavin Ha, Yoichiro Mitsuishi, Luis Corrales-Rodriguez, Maya K. Gelbard, July Rodriguez, Giulio Genovese, Jacqueline Watson, Anwesha Nag, Aaron R. Thorner, Nick Patterson, Giovanny Soca-Chafre, and Jian Carrot-Zhang

Abstract

Supplementary Figures

Published
2023
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