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1. Identification of acquired Notch3 dependency in metastatic Head and Neck Cancer

Author

Kondratyev, Maria, Pesic, Aleksandra, Ketela, Troy, Stickle, Natalie, Beswick, Christine, Shalev, Zvi, Marastoni, Stefano, Samadian, Soroush, Dvorkin-Gheva, Anna, Sayad, Azin, Bashkurov, Mikhail, Boasquevisque, Pedro, Datti, Alessandro, Pugh, Trevor J., Virtanen, Carl, Moffat, Jason, Grénman, Reidar A., Koritzinsky, Marianne, and Wouters, Bradly G.

Published
2023
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4. A clinical laboratory–developed LSC17 stemness score assay for rapid risk assessment of patients with acute myeloid leukemia

Author

Ng, Stanley W.K., Murphy, Tracy, King, Ian, Zhang, Tong, Mah, Michelle, Lu, Zhibin, Stickle, Natalie, Ibrahimova, Narmin, Arruda, Andrea, Mitchell, Amanda, Mai, Ming, He, Rong, Madala, Bindu Swapna, Viswanatha, David S., Dick, John E., Chan, Steven, Virtanen, Carl, Minden, Mark D., Mercer, Timothy, Stockley, Tracy, and Wang, Jean C.Y.

Published
2022
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5. The Prevent Ovarian Cancer Program (POCP): Identification of women at risk for ovarian cancer using complementary recruitment approaches

Author

Tone, Alicia A., McCuaig, Jeanna M., Ricker, Nicole, Boghosian, Talin, Romagnuolo, Tina, Stickle, Natalie, Virtanen, Carl, Zhang, Tong, Kim, Raymond H., Ferguson, Sarah E., May, Taymaa, Laframboise, Stephane, Armel, Susan, Demsky, Rochelle, Volenik, Alexandra, Stuart-McEwan, Terri, Shaw, Patricia, Oza, Amit, Kamel-Reid, Suzanne, Stockley, Tracy, and Bernardini, Marcus Q.

Published
2021
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8. Data from AACR Project GENIE: Powering Precision Medicine through an International Consortium

Author

André, Fabrice, primary, Arnedos, Monica, primary, Baras, Alexander S., primary, Baselga, José, primary, Bedard, Philippe L., primary, Berger, Michael F., primary, Bierkens, Mariska, primary, Calvo, Fabien, primary, Cerami, Ethan, primary, Chakravarty, Debyani, primary, Dang, Kristen K., primary, Davidson, Nancy E., primary, Del Vecchio Fitz, Catherine, primary, Dogan, Semih, primary, DuBois, Raymond N., primary, Ducar, Matthew D., primary, Futreal, P. Andrew, primary, Gao, Jianjiong, primary, Garcia, Francisco, primary, Gardos, Stu, primary, Gocke, Christopher D., primary, Gross, Benjamin E., primary, Guinney, Justin, primary, Heins, Zachary J., primary, Hintzen, Stephanie, primary, Horlings, Hugo, primary, Hudeček, Jan, primary, Hyman, David M., primary, Kamel-Reid, Suzanne, primary, Kandoth, Cyriac, primary, Kinyua, Walter, primary, Kumari, Priti, primary, Kundra, Ritika, primary, Ladanyi, Marc, primary, Lefebvre, Céline, primary, LeNoue-Newton, Michele L., primary, Lepisto, Eva M., primary, Levy, Mia A., primary, Lindeman, Neal I., primary, Lindsay, James, primary, Liu, David, primary, Lu, Zhibin, primary, MacConaill, Laura E., primary, Maurer, Ian, primary, Maxwell, David S., primary, Meijer, Gerrit A., primary, Meric-Bernstam, Funda, primary, Micheel, Christine M., primary, Miller, Clinton, primary, Mills, Gordon, primary, Moore, Nathanael D., primary, Nederlof, Petra M., primary, Omberg, Larsson, primary, Orechia, John A., primary, Park, Ben Ho, primary, Pugh, Trevor J., primary, Reardon, Brendan, primary, Rollins, Barrett J., primary, Routbort, Mark J., primary, Sawyers, Charles L., primary, Schrag, Deborah, primary, Schultz, Nikolaus, primary, Shaw, Kenna R Mills, primary, Shivdasani, Priyanka, primary, Siu, Lillian L., primary, Solit, David B., primary, Sonke, Gabe S., primary, Soria, Jean Charles, primary, Sripakdeevong, Parin, primary, Stickle, Natalie H., primary, Stricker, Thomas P., primary, Sweeney, Shawn M., primary, Taylor, Barry S., primary, ten Hoeve, Jelle J., primary, Thomas, Stacy B., primary, Van Allen, Eliezer M., primary, Van 'T Veer, Laura J., primary, van de Velde, Tony, primary, van Tinteren, Harm, primary, Velculescu, Victor E., primary, Virtanen, Carl, primary, Voest, Emile E., primary, Wang, Lucy L., primary, Wathoo, Chetna, primary, Watt, Stuart, primary, Yu, Celeste, primary, Yu, Thomas V., primary, Yu, Emily, primary, Zehir, Ahmet, primary, and Zhang, Hongxin, primary

Published
2023
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9. Table S3 from AACR Project GENIE: Powering Precision Medicine through an International Consortium

Author

André, Fabrice, primary, Arnedos, Monica, primary, Baras, Alexander S., primary, Baselga, José, primary, Bedard, Philippe L., primary, Berger, Michael F., primary, Bierkens, Mariska, primary, Calvo, Fabien, primary, Cerami, Ethan, primary, Chakravarty, Debyani, primary, Dang, Kristen K., primary, Davidson, Nancy E., primary, Del Vecchio Fitz, Catherine, primary, Dogan, Semih, primary, DuBois, Raymond N., primary, Ducar, Matthew D., primary, Futreal, P. Andrew, primary, Gao, Jianjiong, primary, Garcia, Francisco, primary, Gardos, Stu, primary, Gocke, Christopher D., primary, Gross, Benjamin E., primary, Guinney, Justin, primary, Heins, Zachary J., primary, Hintzen, Stephanie, primary, Horlings, Hugo, primary, Hudeček, Jan, primary, Hyman, David M., primary, Kamel-Reid, Suzanne, primary, Kandoth, Cyriac, primary, Kinyua, Walter, primary, Kumari, Priti, primary, Kundra, Ritika, primary, Ladanyi, Marc, primary, Lefebvre, Céline, primary, LeNoue-Newton, Michele L., primary, Lepisto, Eva M., primary, Levy, Mia A., primary, Lindeman, Neal I., primary, Lindsay, James, primary, Liu, David, primary, Lu, Zhibin, primary, MacConaill, Laura E., primary, Maurer, Ian, primary, Maxwell, David S., primary, Meijer, Gerrit A., primary, Meric-Bernstam, Funda, primary, Micheel, Christine M., primary, Miller, Clinton, primary, Mills, Gordon, primary, Moore, Nathanael D., primary, Nederlof, Petra M., primary, Omberg, Larsson, primary, Orechia, John A., primary, Park, Ben Ho, primary, Pugh, Trevor J., primary, Reardon, Brendan, primary, Rollins, Barrett J., primary, Routbort, Mark J., primary, Sawyers, Charles L., primary, Schrag, Deborah, primary, Schultz, Nikolaus, primary, Shaw, Kenna R Mills, primary, Shivdasani, Priyanka, primary, Siu, Lillian L., primary, Solit, David B., primary, Sonke, Gabe S., primary, Soria, Jean Charles, primary, Sripakdeevong, Parin, primary, Stickle, Natalie H., primary, Stricker, Thomas P., primary, Sweeney, Shawn M., primary, Taylor, Barry S., primary, ten Hoeve, Jelle J., primary, Thomas, Stacy B., primary, Van Allen, Eliezer M., primary, Van 'T Veer, Laura J., primary, van de Velde, Tony, primary, van Tinteren, Harm, primary, Velculescu, Victor E., primary, Virtanen, Carl, primary, Voest, Emile E., primary, Wang, Lucy L., primary, Wathoo, Chetna, primary, Watt, Stuart, primary, Yu, Celeste, primary, Yu, Thomas V., primary, Yu, Emily, primary, Zehir, Ahmet, primary, and Zhang, Hongxin, primary

Published
2023
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10. Supplemental Methods, Supplemental Tables 1-2, Supplemental Figures 1-4 from AACR Project GENIE: Powering Precision Medicine through an International Consortium

Author

André, Fabrice, primary, Arnedos, Monica, primary, Baras, Alexander S., primary, Baselga, José, primary, Bedard, Philippe L., primary, Berger, Michael F., primary, Bierkens, Mariska, primary, Calvo, Fabien, primary, Cerami, Ethan, primary, Chakravarty, Debyani, primary, Dang, Kristen K., primary, Davidson, Nancy E., primary, Del Vecchio Fitz, Catherine, primary, Dogan, Semih, primary, DuBois, Raymond N., primary, Ducar, Matthew D., primary, Futreal, P. Andrew, primary, Gao, Jianjiong, primary, Garcia, Francisco, primary, Gardos, Stu, primary, Gocke, Christopher D., primary, Gross, Benjamin E., primary, Guinney, Justin, primary, Heins, Zachary J., primary, Hintzen, Stephanie, primary, Horlings, Hugo, primary, Hudeček, Jan, primary, Hyman, David M., primary, Kamel-Reid, Suzanne, primary, Kandoth, Cyriac, primary, Kinyua, Walter, primary, Kumari, Priti, primary, Kundra, Ritika, primary, Ladanyi, Marc, primary, Lefebvre, Céline, primary, LeNoue-Newton, Michele L., primary, Lepisto, Eva M., primary, Levy, Mia A., primary, Lindeman, Neal I., primary, Lindsay, James, primary, Liu, David, primary, Lu, Zhibin, primary, MacConaill, Laura E., primary, Maurer, Ian, primary, Maxwell, David S., primary, Meijer, Gerrit A., primary, Meric-Bernstam, Funda, primary, Micheel, Christine M., primary, Miller, Clinton, primary, Mills, Gordon, primary, Moore, Nathanael D., primary, Nederlof, Petra M., primary, Omberg, Larsson, primary, Orechia, John A., primary, Park, Ben Ho, primary, Pugh, Trevor J., primary, Reardon, Brendan, primary, Rollins, Barrett J., primary, Routbort, Mark J., primary, Sawyers, Charles L., primary, Schrag, Deborah, primary, Schultz, Nikolaus, primary, Shaw, Kenna R Mills, primary, Shivdasani, Priyanka, primary, Siu, Lillian L., primary, Solit, David B., primary, Sonke, Gabe S., primary, Soria, Jean Charles, primary, Sripakdeevong, Parin, primary, Stickle, Natalie H., primary, Stricker, Thomas P., primary, Sweeney, Shawn M., primary, Taylor, Barry S., primary, ten Hoeve, Jelle J., primary, Thomas, Stacy B., primary, Van Allen, Eliezer M., primary, Van 'T Veer, Laura J., primary, van de Velde, Tony, primary, van Tinteren, Harm, primary, Velculescu, Victor E., primary, Virtanen, Carl, primary, Voest, Emile E., primary, Wang, Lucy L., primary, Wathoo, Chetna, primary, Watt, Stuart, primary, Yu, Celeste, primary, Yu, Thomas V., primary, Yu, Emily, primary, Zehir, Ahmet, primary, and Zhang, Hongxin, primary

Published
2023
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11. Supplemental File 1 from AACR Project GENIE: Powering Precision Medicine through an International Consortium

Author

André, Fabrice, primary, Arnedos, Monica, primary, Baras, Alexander S., primary, Baselga, José, primary, Bedard, Philippe L., primary, Berger, Michael F., primary, Bierkens, Mariska, primary, Calvo, Fabien, primary, Cerami, Ethan, primary, Chakravarty, Debyani, primary, Dang, Kristen K., primary, Davidson, Nancy E., primary, Del Vecchio Fitz, Catherine, primary, Dogan, Semih, primary, DuBois, Raymond N., primary, Ducar, Matthew D., primary, Futreal, P. Andrew, primary, Gao, Jianjiong, primary, Garcia, Francisco, primary, Gardos, Stu, primary, Gocke, Christopher D., primary, Gross, Benjamin E., primary, Guinney, Justin, primary, Heins, Zachary J., primary, Hintzen, Stephanie, primary, Horlings, Hugo, primary, Hudeček, Jan, primary, Hyman, David M., primary, Kamel-Reid, Suzanne, primary, Kandoth, Cyriac, primary, Kinyua, Walter, primary, Kumari, Priti, primary, Kundra, Ritika, primary, Ladanyi, Marc, primary, Lefebvre, Céline, primary, LeNoue-Newton, Michele L., primary, Lepisto, Eva M., primary, Levy, Mia A., primary, Lindeman, Neal I., primary, Lindsay, James, primary, Liu, David, primary, Lu, Zhibin, primary, MacConaill, Laura E., primary, Maurer, Ian, primary, Maxwell, David S., primary, Meijer, Gerrit A., primary, Meric-Bernstam, Funda, primary, Micheel, Christine M., primary, Miller, Clinton, primary, Mills, Gordon, primary, Moore, Nathanael D., primary, Nederlof, Petra M., primary, Omberg, Larsson, primary, Orechia, John A., primary, Park, Ben Ho, primary, Pugh, Trevor J., primary, Reardon, Brendan, primary, Rollins, Barrett J., primary, Routbort, Mark J., primary, Sawyers, Charles L., primary, Schrag, Deborah, primary, Schultz, Nikolaus, primary, Shaw, Kenna R Mills, primary, Shivdasani, Priyanka, primary, Siu, Lillian L., primary, Solit, David B., primary, Sonke, Gabe S., primary, Soria, Jean Charles, primary, Sripakdeevong, Parin, primary, Stickle, Natalie H., primary, Stricker, Thomas P., primary, Sweeney, Shawn M., primary, Taylor, Barry S., primary, ten Hoeve, Jelle J., primary, Thomas, Stacy B., primary, Van Allen, Eliezer M., primary, Van 'T Veer, Laura J., primary, van de Velde, Tony, primary, van Tinteren, Harm, primary, Velculescu, Victor E., primary, Virtanen, Carl, primary, Voest, Emile E., primary, Wang, Lucy L., primary, Wathoo, Chetna, primary, Watt, Stuart, primary, Yu, Celeste, primary, Yu, Thomas V., primary, Yu, Emily, primary, Zehir, Ahmet, primary, and Zhang, Hongxin, primary

Published
2023
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13. The LSC17 Score Correlates with the ELN 2022 Classification of AML and Is an Independent Predictor of Detectable Measurable Residual Disease after Induction Chemotherapy

Author

Murphy, Tracy, primary, Ng, Stanley W.K., additional, King, Ian, additional, Zhang, Tong, additional, Arruda, Andrea, additional, Claudio, Jaime, additional, Pan, Kristele, additional, Rockwell, Chantal, additional, Lu, Zhibin, additional, Stickle, Natalie, additional, Virtanen, Carl, additional, Gupta, Vikas, additional, Maze, Dawn, additional, McNamara, Caroline, additional, Schimmer, Aaron D., additional, Schuh, Andre C., additional, Sibai, Hassan, additional, Yee, Karen, additional, Khalaf, Dina, additional, Leber, Brian, additional, Sabloff, Mitchell, additional, Tierens, Anne, additional, Minden, Mark D., additional, Stockley, Tracy L., additional, Chan, Steven, additional, and Wang, Jean C.Y., additional

Published
2022
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15. Diversity in the Expressed Genomic Host Response to Myocardial Infarction

Author

Toma, Augustin, primary, dos Santos, Claudia, additional, Burzyńska, Beata, additional, Góra, Monika, additional, Kiliszek, Marek, additional, Stickle, Natalie, additional, Kirsten, Holger, additional, Kosyakovsky, Leah B., additional, Wang, Bo, additional, van Diepen, Sean, additional, Epelman, Slava, additional, Szekely, Yishay, additional, Marshall, John C., additional, Billia, Filio, additional, and Lawler, Patrick R., additional

Published
2022
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16. The Prevent Ovarian Cancer Program (POCP): Identification of Women at Risk for Ovarian Cancer Using Complementary Recruitment Approaches

Author

Tone, Alicia A., primary, McCuaig, Jeanna M., additional, Ricker, Nicole, additional, Boghosian, Talin, additional, Romagnuolo, Tina, additional, Stickle, Natalie, additional, Virtanen, Carl, additional, Zhang, Tong, additional, Kim, Raymond H., additional, Ferguson, Sarah E., additional, May, Taymaa, additional, Laframboise, Stephane, additional, Armel, Susan, additional, Demsky, Rochelle, additional, Volenik, Alexandra, additional, Stuart-McEwan, Terri, additional, Shaw, Patricia, additional, Oza, Amit, additional, Kamel-Reid, Suzanne, additional, Stockley, Tracy, additional, and Bernardini, Marcus Q., additional

Published
2021
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18. Inferior Outcomes with a High LSC17 Score Can be Improved with Flag-IDA

Author

Murphy, Tracy, primary, Ng, Stanley W.K., additional, King, Ian, additional, Zhang, Tong, additional, Arruda, Andrea, additional, Ibrahimova, Narmin, additional, Claudio, Jaime O., additional, Ferrera, Fiona, additional, Pan, Kristele, additional, Rockwell, Chantal, additional, Lu, Zhibin, additional, Stickle, Natalie, additional, Virtanen, Carl, additional, Gupta, Vikas, additional, Maze, Dawn, additional, McNamara, Caroline J, additional, Schimmer, Aaron D, additional, Schuh, Andre C., additional, Sibai, Hassan, additional, Yee, Karen W.L., additional, Khalaf, Dina, additional, Leber, Brian, additional, Sabloff, Mitchell, additional, Tierens, Anne, additional, Minden, Mark D., additional, Stockley, Tracy L., additional, Chan, Steven M, additional, and Wang, Jean C.Y., additional

Published
2020
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22. Trial in Progress: Feasibility and Validation Study of the LSC17 Score in Acute Myeloid Leukemia Patients

Author

Murphy, Tracy, primary, Ng, Stanley W.K., additional, Zhang, Tong, additional, King, Ian, additional, Arruda, Andrea, additional, Claudio, Jaime O., additional, Ibrahimova, Narmin, additional, Ferrera, Fiona, additional, Rockwell, Chantal, additional, Lu, Zhibin, additional, Stickle, Natalie, additional, Virtanen, Carl, additional, Leber, Brian, additional, Sabloff, Mitchell, additional, Minden, Mark D., additional, Stockley, Tracy L., additional, Chan, Steven M, additional, and Wang, Jean C.Y., additional

Published
2019
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24. Abstract 3054: Cell surface targets in head and neck cancer

Author

Kondratyev, Maria, primary, Pesic, Aleksandra, additional, Sayad, Azin, additional, Ketela, Troy, additional, Stickle, Natalie, additional, Virtanen, Carl, additional, Moffat, Jason, additional, Ailles, Laurie, additional, Koritzinsky, Marianne, additional, and Wouters, Brad, additional

Published
2019
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25. Somatic Tumor Variant Filtration Strategies to Optimize Tumor-Only Molecular Profiling Using Targeted Next-Generation Sequencing Panels

Author

Sukhai, Mahadeo A., primary, Misyura, Maksym, additional, Thomas, Mariam, additional, Garg, Swati, additional, Zhang, Tong, additional, Stickle, Natalie, additional, Virtanen, Carl, additional, Bedard, Philippe L., additional, Siu, Lillian L., additional, Smets, Tina, additional, Thijs, Gert, additional, Van Vooren, Steven, additional, Kamel-Reid, Suzanne, additional, and Stockley, Tracy L., additional

Published
2019
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27. Tumor and germline next generation sequencing in high grade serous cancer: experience from a large population‐based testing program.

Author

Care, Melanie, McCuaig, Jeanna, Clarke, Blaise, Grenier, Sylvie, Kim, Raymond H, Rouzbahman, Marjan, Stickle, Natalie, Bernardini, Marcus, and Stockley, Tracy L.

Abstract

The aim of this study was to determine the prevalence of somatic and germline pathogenic variants (PVs) in high‐grade serous cancer (HGSC) and to demonstrate the technical feasibility and effectiveness of a large‐scale, population‐based tumor testing program. It involved a retrospective review of genetic test results in 600 consecutive HGSC tumor samples and a subsequent comparison of germline and tumor results in a subset of 200 individuals. Tumor testing was successful in 95% of samples (570/600) with at least one BRCA1/2 PV identified in 16% (93/570) of cases. Among the 200 paired cases, BRCA1/2 PVs were detected in 38 tumors (19%); 58% were somatic (22/38); and 42% were germline (16/38). There was 100% concordance between germline and tumor test results. This is the largest series of BRCA1/2 testing in HGSC (tumor‐only and paired cohorts), reported to date, and our data show that an effectively designed and validated population‐based tumor testing program can be used to determine both treatment eligibility and hereditary cancer risk. [ABSTRACT FROM AUTHOR]

Published
2021
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28. Abstract 407: Novel targets in metastatic HNSCC

Author

Kondratyev, Maria, primary, Pesic, Aleksandra, additional, Ketela, Troy, additional, Sayad, Azin, additional, Marastoni, Stephano, additional, Mofat, Jason, additional, Virtanen, Carl, additional, Stickle, Natalie, additional, Grenman, Reider, additional, and Wouters, Brad, additional

Published
2018
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29. Identification of Acquired Notch3 Dependency in Metastatic Head and Neck Cancer

Author

Kondratyev, Maria, primary, Pesic, Aleksandra, additional, Sayad, Azin, additional, Ketela, Troy, additional, Stickle, Natalie, additional, Beswick, Christine, additional, Shalev, Zvi, additional, Marastoni, Stefano, additional, Samadian, Soroush, additional, Bashkurov, Mikhail, additional, Boasquevisque, Pedro, additional, Datti, Alessandro, additional, Pugh, Trevor J., additional, Virtanen, Carl, additional, Moffat, Jason, additional, Grénman, Reidar A., additional, Koritzinsky, Marianne, additional, and Wouters, Bradly G., additional

Published
2018
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31. Efficient generation of patient-matched malignant and normal primary cell cultures from clear cell renal cell carcinoma patients: clinically relevant models for research and personalized medicine

Author

Lobo, Nazleen C., primary, Gedye, Craig, additional, Apostoli, Anthony J., additional, Brown, Kevin R., additional, Paterson, Joshua, additional, Stickle, Natalie, additional, Robinette, Michael, additional, Fleshner, Neil, additional, Hamilton, Robert J., additional, Kulkarni, Girish, additional, Zlotta, Alexandre, additional, Evans, Andrew, additional, Finelli, Antonio, additional, Moffat, Jason, additional, Jewett, Michael A. S., additional, and Ailles, Laurie, additional

Published
2016
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36. Additional file 10: Figure S1. of Efficient generation of patient-matched malignant and normal primary cell cultures from clear cell renal cell carcinoma patients: clinically relevant models for research and personalized medicine

Author

Nazleen Lobo, Gedye, Craig, Apostoli, Anthony, Brown, Kevin, Paterson, Joshua, Stickle, Natalie, Robinette, Michael, Fleshner, Neil, Hamilton, Robert, Girish Kulkarni, Zlotta, Alexandre, Evans, Andrew, Finelli, Antonio, Moffat, Jason, Jewett, Michael, and Ailles, Laurie

Subjects
3. Good health
Abstract

Copy number profiles of primary cultures and matched primary tumors and adjacent normal tissues. Figure S2. Morphology of VHLmut vs. VHLwt cultures. Figure S3. VHLwt cells do not express distal tubule markers. Figure S4. Xenografts derived from RCC#243mut and RCC#407mut cultures. Figure S5. Hierarchical clustering heatmap of Pearson correlation coefficients between matched VHLmut cells, VHLwt cells and primary tumor tissues. Figure S6. Functional annotation of 211 VHLmut-associated genes (red) and 382 VHLwt-associated genes. Figure S7. Enrichment map of tumor tissue vs. VHLmut culture gene expression profiles. (PPTX 10688 kb)

37. Additional file 10: Figure S1. of Efficient generation of patient-matched malignant and normal primary cell cultures from clear cell renal cell carcinoma patients: clinically relevant models for research and personalized medicine

Author

Nazleen Lobo, Gedye, Craig, Apostoli, Anthony, Brown, Kevin, Paterson, Joshua, Stickle, Natalie, Robinette, Michael, Fleshner, Neil, Hamilton, Robert, Girish Kulkarni, Zlotta, Alexandre, Evans, Andrew, Finelli, Antonio, Moffat, Jason, Jewett, Michael, and Ailles, Laurie

Subjects
3. Good health
Abstract

Copy number profiles of primary cultures and matched primary tumors and adjacent normal tissues. Figure S2. Morphology of VHLmut vs. VHLwt cultures. Figure S3. VHLwt cells do not express distal tubule markers. Figure S4. Xenografts derived from RCC#243mut and RCC#407mut cultures. Figure S5. Hierarchical clustering heatmap of Pearson correlation coefficients between matched VHLmut cells, VHLwt cells and primary tumor tissues. Figure S6. Functional annotation of 211 VHLmut-associated genes (red) and 382 VHLwt-associated genes. Figure S7. Enrichment map of tumor tissue vs. VHLmut culture gene expression profiles. (PPTX 10688 kb)

38. Peroxisome Proliferator-Activated Receptor-δ Supports the Metabolic Requirements of Cell Growth in TCRα-SelectedThymocytes and Peripheral CD4+ T Cells.

Author

Fei Linda Zhao, Ahn, Jeeyoon Jennifer, Chen, Edward L. Y., Tae Joon Yi, Stickle, Natalie H., David Spaner, David Z, Zúñiga-Pflücker, Juan Carlos, and Dunn, Shannon E.

Subjects
*T cells, *CELL cycle, *CELL growth, *THYMOCYTES, *CELL proliferation, *PROGENITOR cells, *CD4 antigen, *MICE
Abstract

During T cell development, progenitor thymocytes undergo a large proliferative burst immediately following successful TCRb rearrangement, and defects in genes that regulate this proliferation have a profound effect on thymus cellularity and output. Although the signaling pathways that initiate cell cycling and nutrient uptake after TCRb selection are understood, less is known about the transcriptional programs that regulate the metabolic machinery to promote biomass accumulation during this process. In this article, we report that mice with whole body deficiency in the nuclear receptor peroxisome proliferator-activated receptor-δ (PPARδmut) exhibit a reduction in spleen and thymus cellularity, with a decrease in thymocyte cell number starting at the double-negative 4 stage of thymocyte development. Although in vivo DNA synthesis was normal in PPARδmut thymocytes, studies in the OP9-δelta-like 4 in vitro system of differentiation revealed that PPARδmut double-negative 3 cells underwent fewer cell divisions. Naive CD4+ T cells from PPARδmut mice also exhibited reduced proliferation upon TCR and CD28 stimulation in vitro. Growth defects in PPAR-δ-δeficient thymocytes and peripheral CD4+ T cells correlated with decreases in extracellular acidification rate, mitochondrial reserve, and expression of a host of genes involved in glycolysis, oxidative phosphorylation, and lipogenesis. By contrast, mice with T cell-restricted deficiency of Ppard starting at the double-positive stage of thymocyte development, although exhibiting defective CD4+ T cell growth, possessed a normal T cell compartment, pointing to developmental defects as a cause of peripheral T cell lymphopenia in PPARδmut mice. These findings implicate PPAR-δ as a regulator of the metabolic program during thymocyte and T cell growth. [ABSTRACT FROM AUTHOR]

Published
2018
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39. Peroxisome Proliferator-Activated Receptor-δ Supports the Metabolic Requirements of Cell Growth in TCRβ-Selected Thymocytes and Peripheral CD4 + T Cells.

Author

Zhao FL, Ahn JJ, Chen ELY, Yi TJ, Stickle NH, Spaner D, Zúñiga-Pflücker JC, and Dunn SE

Subjects
Animals, CD4-Positive T-Lymphocytes immunology, Cell Proliferation physiology, Gene Rearrangement, beta-Chain T-Cell Antigen Receptor, Mice, Mice, Inbred C57BL, Receptors, Antigen, T-Cell, alpha-beta immunology, Thymocytes immunology, CD4-Positive T-Lymphocytes metabolism, Cell Differentiation immunology, Receptors, Cytoplasmic and Nuclear metabolism, Thymocytes metabolism
Abstract

During T cell development, progenitor thymocytes undergo a large proliferative burst immediately following successful TCRβ rearrangement, and defects in genes that regulate this proliferation have a profound effect on thymus cellularity and output. Although the signaling pathways that initiate cell cycling and nutrient uptake after TCRβ selection are understood, less is known about the transcriptional programs that regulate the metabolic machinery to promote biomass accumulation during this process. In this article, we report that mice with whole body deficiency in the nuclear receptor peroxisome proliferator-activated receptor-δ (PPARδ mut ) exhibit a reduction in spleen and thymus cellularity, with a decrease in thymocyte cell number starting at the double-negative 4 stage of thymocyte development. Although in vivo DNA synthesis was normal in PPARδ mut thymocytes, studies in the OP9-delta-like 4 in vitro system of differentiation revealed that PPARδ mut double-negative 3 cells underwent fewer cell divisions. Naive CD4 + T cells from PPARδ mut mice also exhibited reduced proliferation upon TCR and CD28 stimulation in vitro. Growth defects in PPAR-δ-deficient thymocytes and peripheral CD4 + T cells correlated with decreases in extracellular acidification rate, mitochondrial reserve, and expression of a host of genes involved in glycolysis, oxidative phosphorylation, and lipogenesis. By contrast, mice with T cell-restricted deficiency of Ppard starting at the double-positive stage of thymocyte development, although exhibiting defective CD4 + T cell growth, possessed a normal T cell compartment, pointing to developmental defects as a cause of peripheral T cell lymphopenia in PPARδ mut mice. These findings implicate PPAR-δ as a regulator of the metabolic program during thymocyte and T cell growth., (Copyright © 2018 by The American Association of Immunologists, Inc.)

Published
2018
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