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17 results on '"Rao, Aparna D."'

1. Adaptive translational reprogramming of metabolism limits the response to targeted therapy in BRAFV600 melanoma

Author

Smith, Lorey K., Parmenter, Tiffany, Kleinschmidt, Margarete, Kusnadi, Eric P., Kang, Jian, Martin, Claire A., Lau, Peter, Patel, Riyaben, Lorent, Julie, Papadopoli, David, Trigos, Anna, Ward, Teresa, Rao, Aparna D., Lelliott, Emily J., Sheppard, Karen E., Goode, David, Hicks, Rodney J., Tiganis, Tony, Simpson, Kaylene J., Larsson, Ola, Blythe, Benjamin, Cullinane, Carleen, Wickramasinghe, Vihandha O., Pearson, Richard B., and McArthur, Grant A.

Published
2022
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2. Correction: Regulation of PRMT5–MDM4 axis is critical in the response to CDK4/6 inhibitors in melanoma

Author

AbuHammad, Shatha, Cullinane, Carleen, Martin, Claire, Bacolas, Zoe, Ward, Teresa, Chen, Huiqin, Slater, Alison, Ardley, Kerry, Kirby, Laura, Chan, Keefe T., Brajanovski, Natalie, Smith, Lorey K., Rao, Aparna D., Lelliott, Emily J., Kleinschmidt, Margarete, Vergara, Ismael A., Papenfuss, Anthony T., Lau, Peter, Ghosh, Prerana, Haupt, Sue, Haupt, Ygal, Sanij, Elaine, Poortinga, Gretchen, Pearson, Richard B., Falk, Hendrik, Curtis, David J., Stupple, Paul, Devlin, Mark, Street, Ian, Davies, Michael A., McArthur, Grant A., and Sheppard, Karen E.

Published
2020

3. Regulation of PRMT5–MDM4 axis is critical in the response to CDK4/6 inhibitors in melanoma

Author

AbuHammad, Shatha, Cullinane, Carleen, Martin, Claire, Bacolas, Zoe, Ward, Teresa, Chen, Huiqin, Slater, Alison, Ardley, Kerry, Kirby, Laura, Chan, Keefe T., Brajanovski, Natalie, Smith, Lorey K., Rao, Aparna D., Lelliott, Emily J., Kleinschmidt, Margarete, Vergara, Ismael A., Papenfuss, Anthony T., Lau, Peter, Ghosh, Prerana, Haupt, Sue, Haupt, Ygal, Sanij, Elaine, Poortinga, Gretchen, Pearson, Richard B., Falk, Hendrik, Curtis, David J., Stupple, Paul, Devlin, Mark, Street, Ian, Davies, Michael A., McArthur, Grant A., and Sheppard, Karen E.

Published
2019

5. Supplementary Figure from A Short Isoform of Spermatogenic Enzyme GAPDHS Functions as a Metabolic Switch and Limits Metastasis in Melanoma

Author

Gill, Jennifer G., primary, Leef, Samantha N., primary, Ramesh, Vijayashree, primary, Martin-Sandoval, Misty S., primary, Rao, Aparna D., primary, West, Lindsey, primary, Muh, Sarah, primary, Gu, Wen, primary, Zhao, Zhiyu, primary, Hosler, Gregory A., primary, Vandergriff, Travis W., primary, Durham, Alison B., primary, Mathews, Thomas P., primary, and Aurora, Arin B., primary

Published
2023
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6. Supplementary Table from A Short Isoform of Spermatogenic Enzyme GAPDHS Functions as a Metabolic Switch and Limits Metastasis in Melanoma

Author

Gill, Jennifer G., primary, Leef, Samantha N., primary, Ramesh, Vijayashree, primary, Martin-Sandoval, Misty S., primary, Rao, Aparna D., primary, West, Lindsey, primary, Muh, Sarah, primary, Gu, Wen, primary, Zhao, Zhiyu, primary, Hosler, Gregory A., primary, Vandergriff, Travis W., primary, Durham, Alison B., primary, Mathews, Thomas P., primary, and Aurora, Arin B., primary

Published
2023
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7. Data from A Short Isoform of Spermatogenic Enzyme GAPDHS Functions as a Metabolic Switch and Limits Metastasis in Melanoma

Author

Gill, Jennifer G., primary, Leef, Samantha N., primary, Ramesh, Vijayashree, primary, Martin-Sandoval, Misty S., primary, Rao, Aparna D., primary, West, Lindsey, primary, Muh, Sarah, primary, Gu, Wen, primary, Zhao, Zhiyu, primary, Hosler, Gregory A., primary, Vandergriff, Travis W., primary, Durham, Alison B., primary, Mathews, Thomas P., primary, and Aurora, Arin B., primary

Published
2023
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8. In vivo characterization of glutamine metabolism identifies therapeutic targets in clear cell renal cell carcinoma

Author

Kaushik, Akash K., primary, Tarangelo, Amy, additional, Boroughs, Lindsey K., additional, Ragavan, Mukundan, additional, Zhang, Yuanyuan, additional, Wu, Cheng-Yang, additional, Li, Xiangyi, additional, Ahumada, Kristen, additional, Chiang, Jui-Chung, additional, Tcheuyap, Vanina T., additional, Saatchi, Faeze, additional, Do, Quyen N., additional, Yong, Cissy, additional, Rosales, Tracy, additional, Stevens, Christina, additional, Rao, Aparna D., additional, Faubert, Brandon, additional, Pachnis, Panayotis, additional, Zacharias, Lauren G., additional, Vu, Hieu, additional, Cai, Feng, additional, Mathews, Thomas P., additional, Genovese, Giannicola, additional, Slusher, Barbara S., additional, Kapur, Payal, additional, Sun, Xiankai, additional, Merritt, Matthew, additional, Brugarolas, James, additional, and DeBerardinis, Ralph J., additional

Published
2022
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10. Cancer Metabolism

Author

Pavlova, Natalya N., primary, Rao, Aparna D., additional, DeBerardinis, Ralph J., additional, and Thompson, Craig B., additional

Published
2022
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11. In vivo isotope tracing reveals a requirement for the electron transport chain in glucose and glutamine metabolism by tumors

Author

Pachnis, Panayotis, primary, Wu, Zheng, additional, Faubert, Brandon, additional, Tasdogan, Alpaslan, additional, Gu, Wen, additional, Shelton, Spencer, additional, Solmonson, Ashley, additional, Rao, Aparna D., additional, Kaushik, Akash K., additional, Rogers, Thomas J., additional, Ubellacker, Jessalyn M., additional, LaVigne, Collette A., additional, Yang, Chendong, additional, Ko, Bookyung, additional, Ramesh, Vijayashree, additional, Sudderth, Jessica, additional, Zacharias, Lauren G., additional, Martin-Sandoval, Misty S., additional, Do, Duyen, additional, Mathews, Thomas P., additional, Zhao, Zhiyu, additional, Mishra, Prashant, additional, Morrison, Sean J., additional, and DeBerardinis, Ralph J., additional

Published
2022
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12. A Short Isoform of Spermatogenic Enzyme GAPDHS Functions as a Metabolic Switch and Limits Metastasis in Melanoma

Author

Gill, Jennifer G., primary, Leef, Samantha N., additional, Ramesh, Vijayashree, additional, Martin-Sandoval, Misty S., additional, Rao, Aparna D., additional, West, Lindsey, additional, Muh, Sarah, additional, Gu, Wen, additional, Zhao, Zhiyu, additional, Hosler, Gregory A., additional, Vandergriff, Travis W., additional, Durham, Alison B., additional, Mathews, Thomas P., additional, and Aurora, Arin B., additional

Published
2022
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13. Adaptive translational reprogramming of metabolism limits the response to targeted therapy in BRAFV600 melanoma.

Author

Smith, Lorey K., Parmenter, Tiffany, Kleinschmidt, Margarete, Kusnadi, Eric P., Kang, Jian, Martin, Claire A., Lau, Peter, Patel, Riyaben, Lorent, Julie, Papadopoli, David, Trigos, Anna, Ward, Teresa, Rao, Aparna D., Lelliott, Emily J., Sheppard, Karen E., Goode, David, Hicks, Rodney J., Tiganis, Tony, Simpson, Kaylene J., and Larsson, Ola

Subjects
MELANOMA, METABOLIC regulation, PROTEIN metabolism, METABOLISM, TREATMENT effectiveness
Abstract

Despite the success of therapies targeting oncogenes in cancer, clinical outcomes are limited by residual disease that ultimately results in relapse. This residual disease is often characterized by non-genetic adaptive resistance, that in melanoma is characterised by altered metabolism. Here, we examine how targeted therapy reprograms metabolism in BRAF-mutant melanoma cells using a genome-wide RNA interference (RNAi) screen and global gene expression profiling. Using this systematic approach we demonstrate post-transcriptional regulation of metabolism following BRAF inhibition, involving selective mRNA transport and translation. As proof of concept we demonstrate the RNA processing kinase U2AF homology motif kinase 1 (UHMK1) associates with mRNAs encoding metabolism proteins and selectively controls their transport and translation during adaptation to BRAF-targeted therapy. UHMK1 inactivation induces cell death by disrupting therapy induced metabolic reprogramming, and importantly, delays resistance to BRAF and MEK combination therapy in multiple in vivo models. We propose selective mRNA processing and translation by UHMK1 constitutes a mechanism of non-genetic resistance to targeted therapy in melanoma by controlling metabolic plasticity induced by therapy. Different adaptive mechanisms have been reported to reduce the efficacy of mutant BRAF inhibition in melanoma. Here, the authors show BRAF inhibition induces the translational regulation of metabolic genes leading to acquired therapy resistance. [ABSTRACT FROM AUTHOR]

Published
2022
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14. Adaptive post-transcriptional reprogramming of metabolism limits response to targeted therapy in BRAFV600 melanoma

Author

Smith, Lorey K, primary, Parmenter, Tiffany, additional, Kleinschmidt, Margarete, additional, Kusnadi, Eric P, additional, Kang, Jian, additional, Martin, Claire A, additional, Lau, Peter, additional, Lorent, Julie, additional, Trigos, Anna, additional, Ward, Teresa, additional, Rao, Aparna D, additional, Lelliott, Emily J, additional, Sheppard, Karen E, additional, Goode, David, additional, Hicks, Rodney J, additional, Tiganis, Tony, additional, Simpson, Kaylene J, additional, Larsson, Ola, additional, Cullinane, Carleen, additional, Wickramasinghe, Vihandha O, additional, Pearson, Richard B, additional, and McArthur, Grant A, additional

Published
2019
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17. In vivo characterization of glutamine metabolism identifies therapeutic targets in clear cell renal cell carcinoma

Author

Akash K. Kaushik, Amy Tarangelo, Lindsey K. Boroughs, Mukundan Ragavan, Yuanyuan Zhang, Cheng-Yang Wu, Xiangyi Li, Kristen Ahumada, Jui-Chung Chiang, Vanina T. Tcheuyap, Faeze Saatchi, Quyen N. Do, Cissy Yong, Tracy Rosales, Christina Stevens, Aparna D. Rao, Brandon Faubert, Panayotis Pachnis, Lauren G. Zacharias, Hieu Vu, Feng Cai, Thomas P. Mathews, Giannicola Genovese, Barbara S. Slusher, Payal Kapur, Xiankai Sun, Matthew Merritt, James Brugarolas, Ralph J. DeBerardinis, Kaushik, Akash K [0000-0002-8200-2370], Tarangelo, Amy [0000-0002-0571-3582], Ragavan, Mukundan [0000-0001-8678-4229], Li, Xiangyi [0000-0002-6157-8047], Chiang, Jui-Chung [0000-0001-9979-8347], Tcheuyap, Vanina T [0000-0002-6817-9241], Saatchi, Faeze [0000-0001-9151-7133], Do, Quyen N [0000-0001-9511-7866], Yong, Cissy [0000-0002-8697-1494], Rosales, Tracy [0000-0002-7285-2427], Rao, Aparna D [0000-0002-6394-0011], Faubert, Brandon [0000-0002-2886-886X], Pachnis, Panayotis [0000-0002-3019-7874], Mathews, Thomas P [0000-0002-9355-8243], Slusher, Barbara S [0000-0001-9814-4157], Sun, Xiankai [0000-0002-5140-6110], Merritt, Matthew [0000-0003-4617-9651], Brugarolas, James [0000-0002-8575-499X], DeBerardinis, Ralph J [0000-0002-2705-7432], and Apollo - University of Cambridge Repository

Subjects
Mice, Multidisciplinary, Glutaminase, Glutamine, Humans, Animals, Carcinoma, Renal Cell, Kidney Neoplasms, Isocitrate Dehydrogenase
Abstract

Targeting metabolic vulnerabilities has been proposed as a therapeutic strategy in renal cell carcinoma (RCC). Here, we analyzed the metabolism of patient-derived xenografts (tumorgrafts) from diverse subtypes of RCC. Tumorgrafts from VHL -mutant clear cell RCC (ccRCC) retained metabolic features of human ccRCC and engaged in oxidative and reductive glutamine metabolism. Genetic silencing of isocitrate dehydrogenase-1 or isocitrate dehydrogenase-2 impaired reductive labeling of tricarboxylic acid (TCA) cycle intermediates in vivo and suppressed growth of tumors generated from tumorgraft-derived cells. Glutaminase inhibition reduced the contribution of glutamine to the TCA cycle and resulted in modest suppression of tumorgraft growth. Infusions with [amide- 15 N]glutamine revealed persistent amidotransferase activity during glutaminase inhibition, and blocking these activities with the amidotransferase inhibitor JHU-083 also reduced tumor growth in both immunocompromised and immunocompetent mice. We conclude that ccRCC tumorgrafts catabolize glutamine via multiple pathways, perhaps explaining why it has been challenging to achieve therapeutic responses in patients by inhibiting glutaminase.

Published
2022

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