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16 results on '"Eric R. Londin"'

1. Table S5. from Posttranscriptional Upregulation of IDH1 by HuR Establishes a Powerful Survival Phenotype in Pancreatic Cancer Cells

Author

Jordan M. Winter, Jonathan R. Brody, Christian M. Metallo, Erin L. Seifert, Eric R. Londin, Charles J. Yeo, Wei Jiang, Joseph A. Cozzitorto, Masaya Jimbo, Saswati N. Chand, Fernando F. Blanco, Cynthia Moffat, Nicole C. Mambelli-Lisboa, Katerina Dukleska, Ali Vaziri-Gohar, Avinoam Nevler, Seth J. Parker, Shruti Lal, and Mahsa Zarei

Abstract

Table S5: Results of RNA sequencing in PDA cell lines (HS-766T and MiaPaCa2) with each modulated by CRISPR/Cas9 to delete HuR expression.

Published
2023

2. Data from Posttranscriptional Upregulation of IDH1 by HuR Establishes a Powerful Survival Phenotype in Pancreatic Cancer Cells

Author

Jordan M. Winter, Jonathan R. Brody, Christian M. Metallo, Erin L. Seifert, Eric R. Londin, Charles J. Yeo, Wei Jiang, Joseph A. Cozzitorto, Masaya Jimbo, Saswati N. Chand, Fernando F. Blanco, Cynthia Moffat, Nicole C. Mambelli-Lisboa, Katerina Dukleska, Ali Vaziri-Gohar, Avinoam Nevler, Seth J. Parker, Shruti Lal, and Mahsa Zarei

Abstract

Cancer aggressiveness may result from the selective pressure of a harsh nutrient-deprived microenvironment. Here we illustrate how such conditions promote chemotherapy resistance in pancreatic ductal adenocarcinoma (PDAC). Glucose or glutamine withdrawal resulted in a 5- to 10-fold protective effect with chemotherapy treatment. PDAC xenografts were less sensitive to gemcitabine in hypoglycemic mice compared with hyperglycemic mice. Consistent with this observation, patients receiving adjuvant gemcitabine (n = 107) with elevated serum glucose levels (HgbA1C > 6.5%) exhibited improved survival. We identified enhanced antioxidant defense as a driver of chemoresistance in this setting. ROS levels were doubled in vitro by either nutrient withdrawal or gemcitabine treatment, but depriving PDAC cells of nutrients before gemcitabine treatment attenuated this effect. Mechanistic investigations based on RNAi or CRISPR approaches implicated the RNA binding protein HuR in preserving survival under nutrient withdrawal, with or without gemcitabine. Notably, RNA deep sequencing and functional analyses in HuR-deficient PDAC cell lines identified isocitrate dehydrogenase 1 (IDH1) as the sole antioxidant enzyme under HuR regulation. HuR-deficient PDAC cells lacked the ability to engraft successfully in immunocompromised mice, but IDH1 overexpression in these cells was sufficient to fully restore chemoresistance under low nutrient conditions. Overall, our findings highlight the HuR–IDH1 regulatory axis as a critical, actionable therapeutic target in pancreatic cancer. Cancer Res; 77(16); 4460–71. ©2017 AACR.

Published
2023

3. Supplemental Information from Posttranscriptional Upregulation of IDH1 by HuR Establishes a Powerful Survival Phenotype in Pancreatic Cancer Cells

Author

Jordan M. Winter, Jonathan R. Brody, Christian M. Metallo, Erin L. Seifert, Eric R. Londin, Charles J. Yeo, Wei Jiang, Joseph A. Cozzitorto, Masaya Jimbo, Saswati N. Chand, Fernando F. Blanco, Cynthia Moffat, Nicole C. Mambelli-Lisboa, Katerina Dukleska, Ali Vaziri-Gohar, Avinoam Nevler, Seth J. Parker, Shruti Lal, and Mahsa Zarei

Abstract

Supplemental Methods and Supplemental Figure Legends

Published
2023

4. Supplementary Figures from Posttranscriptional Upregulation of IDH1 by HuR Establishes a Powerful Survival Phenotype in Pancreatic Cancer Cells

Author

Jordan M. Winter, Jonathan R. Brody, Christian M. Metallo, Erin L. Seifert, Eric R. Londin, Charles J. Yeo, Wei Jiang, Joseph A. Cozzitorto, Masaya Jimbo, Saswati N. Chand, Fernando F. Blanco, Cynthia Moffat, Nicole C. Mambelli-Lisboa, Katerina Dukleska, Ali Vaziri-Gohar, Avinoam Nevler, Seth J. Parker, Shruti Lal, and Mahsa Zarei

Abstract

Supplementary.Figures 1-8

Published
2023

5. Supplementary Video 2 from HuR Posttranscriptionally Regulates WEE1: Implications for the DNA Damage Response in Pancreatic Cancer Cells

Author

Jonathan R. Brody, Timothy J. Yen, Isidore Rigoutsos, Jordan M. Winter, Janet A. Sawicki, Charles J. Yeo, Zoë A. Norris, Masaya Jimbo, Carmella Romeo, Joseph A. Cozzitorto, Eric R. Londin, Vikram Bhattacharjee, Neil Beeharry, Richard A. Burkhart, and Shruti Lal

Abstract

AVI file - 8881KB, siRNA HuR cells progressing through mitosis after MMC treatment.

Published
2023

6. Supplementary Figure 2 from HuR Posttranscriptionally Regulates WEE1: Implications for the DNA Damage Response in Pancreatic Cancer Cells

Author

Jonathan R. Brody, Timothy J. Yen, Isidore Rigoutsos, Jordan M. Winter, Janet A. Sawicki, Charles J. Yeo, Zoë A. Norris, Masaya Jimbo, Carmella Romeo, Joseph A. Cozzitorto, Eric R. Londin, Vikram Bhattacharjee, Neil Beeharry, Richard A. Burkhart, and Shruti Lal

Abstract

PDF file - 658KB, HuR manipulation sensitizes PDA cells to chemotherapeutics agents.

Published
2023

7. Supplementary Video 1 from HuR Posttranscriptionally Regulates WEE1: Implications for the DNA Damage Response in Pancreatic Cancer Cells

Author

Jonathan R. Brody, Timothy J. Yen, Isidore Rigoutsos, Jordan M. Winter, Janet A. Sawicki, Charles J. Yeo, Zoë A. Norris, Masaya Jimbo, Carmella Romeo, Joseph A. Cozzitorto, Eric R. Londin, Vikram Bhattacharjee, Neil Beeharry, Richard A. Burkhart, and Shruti Lal

Abstract

AVI file - 8883KB, siRNA Control cells progressing through mitosis after MMC treatment.

Published
2023

8. Supplementary Figure 5 from HuR Posttranscriptionally Regulates WEE1: Implications for the DNA Damage Response in Pancreatic Cancer Cells

Author

Jonathan R. Brody, Timothy J. Yen, Isidore Rigoutsos, Jordan M. Winter, Janet A. Sawicki, Charles J. Yeo, Zoë A. Norris, Masaya Jimbo, Carmella Romeo, Joseph A. Cozzitorto, Eric R. Londin, Vikram Bhattacharjee, Neil Beeharry, Richard A. Burkhart, and Shruti Lal

Abstract

PDF file - 2070KB, WEE1 is post-transcriptionally regulated by HuR upon DNA damage.

Published
2023

9. Supplementary Figure 3 from HuR Posttranscriptionally Regulates WEE1: Implications for the DNA Damage Response in Pancreatic Cancer Cells

Author

Jonathan R. Brody, Timothy J. Yen, Isidore Rigoutsos, Jordan M. Winter, Janet A. Sawicki, Charles J. Yeo, Zoë A. Norris, Masaya Jimbo, Carmella Romeo, Joseph A. Cozzitorto, Eric R. Londin, Vikram Bhattacharjee, Neil Beeharry, Richard A. Burkhart, and Shruti Lal

Abstract

PDF file - 471KB, HuR silencing induced DNA damage breaks in PL5 cells.

Published
2023

12. Supplementary Video 3 from HuR Posttranscriptionally Regulates WEE1: Implications for the DNA Damage Response in Pancreatic Cancer Cells

Author

Jonathan R. Brody, Timothy J. Yen, Isidore Rigoutsos, Jordan M. Winter, Janet A. Sawicki, Charles J. Yeo, Zoë A. Norris, Masaya Jimbo, Carmella Romeo, Joseph A. Cozzitorto, Eric R. Londin, Vikram Bhattacharjee, Neil Beeharry, Richard A. Burkhart, and Shruti Lal

Abstract

AVI file - 8882KB, Untreated siRNA HuR cells progressing through mitosis.

Published
2023

14. Supplementary Table 1 from HuR Posttranscriptionally Regulates WEE1: Implications for the DNA Damage Response in Pancreatic Cancer Cells

Author

Jonathan R. Brody, Timothy J. Yen, Isidore Rigoutsos, Jordan M. Winter, Janet A. Sawicki, Charles J. Yeo, Zoë A. Norris, Masaya Jimbo, Carmella Romeo, Joseph A. Cozzitorto, Eric R. Londin, Vikram Bhattacharjee, Neil Beeharry, Richard A. Burkhart, and Shruti Lal

Abstract

PDF file - 64KB, Class of drugs used in the drug sensitivity assays performed in MiaPaCa2 cells against siRNA Control and HuR, respective IC50 of each drug identified.

Published
2023

15. CoAIMs: a cost-effective panel of ancestry informative markers for determining continental origins.

Author

Eric R Londin, Margaret A Keller, Cathleen Maista, Gretchen Smith, Laura A Mamounas, Ran Zhang, Steven J Madore, Katrina Gwinn, and Roderick A Corriveau

Subjects
Medicine, Science
Abstract

Genetic ancestry is known to impact outcomes of genotype-phenotype studies that are designed to identify risk for common diseases in human populations. Failure to control for population stratification due to genetic ancestry can significantly confound results of disease association studies. Moreover, ancestry is a critical factor in assessing lifetime risk of disease, and can play an important role in optimizing treatment. As modern medicine moves towards using personal genetic information for clinical applications, it is important to determine genetic ancestry in an accurate, cost-effective and efficient manner. Self-identified race is a common method used to track and control for population stratification; however, social constructs of race are not necessarily informative for genetic applications. The use of ancestry informative markers (AIMs) is a more accurate method for determining genetic ancestry for the purposes of population stratification.Here we introduce a novel panel of 36 microsatellite (MSAT) AIMs that determines continental admixture proportions. This panel, which we have named Continental Ancestry Informative Markers or CoAIMs, consists of MSAT AIMs that were chosen based upon their measure of genetic variance (F(st)), allele frequencies and their suitability for efficient genotyping. Genotype analysis using CoAIMs along with a Bayesian clustering method (STRUCTURE) is able to discern continental origins including Europe/Middle East (Caucasians), East Asia, Africa, Native America, and Oceania. In addition to determining continental ancestry for individuals without significant admixture, we applied CoAIMs to ascertain admixture proportions of individuals of self declared race.CoAIMs can be used to efficiently and effectively determine continental admixture proportions in a sample set. The CoAIMs panel is a valuable resource for genetic researchers performing case-control genetic association studies, as it can control for the confounding effects of population stratification. The MSAT-based approach used here has potential for broad applicability as a cost effective tool toward determining admixture proportions.

Published
2010
Full Text
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16. Integrated Genomic Characterization of Pancreatic Ductal Adenocarcinoma

Author

Benjamin J. Raphael, Ralph H. Hruban, Andrew J. Aguirre, Richard A. Moffitt, Jen Jen Yeh, Chip Stewart, A. Gordon Robertson, Andrew D. Cherniack, Manaswi Gupta, Gad Getz, Stacey B. Gabriel, Matthew Meyerson, Carrie Cibulskis, Suzanne S. Fei, Toshinori Hinoue, Hui Shen, Peter W. Laird, Shiyun Ling, Yiling Lu, Gordon B. Mills, Rehan Akbani, Phillipe Loher, Eric R. Londin, Isidore Rigoutsos, Aristeidis G. Telonis, Ewan A. Gibb, Anna Goldenberg, Aziz M. Mezlini, Katherine A. Hoadley, Eric Collisson, Eric Lander, Bradley A. Murray, Julian Hess, Mara Rosenberg, Louis Bergelson, Hailei Zhang, Juok Cho, Grace Tiao, Jaegil Kim, Dimitri Livitz, Ignaty Leshchiner, Brendan Reardon, Eliezer Van Allen, Atanas Kamburov, Rameen Beroukhim, Gordon Saksena, Steven E. Schumacher, Michael S. Noble, David I. Heiman, Nils Gehlenborg, Michael S. Lawrence, Volkan Adsay, Gloria Petersen, David Klimstra, Nabeel Bardeesy, Mark D.M. Leiserson, Reanne Bowlby, Katayoon Kasaian, Inanc Birol, Karen L. Mungall, Sara Sadeghi, John N. Weinstein, Paul T. Spellman, Yuexin Liu, Laufey T. Amundadottir, Joel Tepper, Aatur D. Singhi, Rajiv Dhir, Drwiega Paul, Thomas Smyrk, Lizhi Zhang, Paula Kim, Jay Bowen, Jessica Frick, Julie M. Gastier-Foster, Mark Gerken, Kevin Lau, Kristen M. Leraas, Tara M. Lichtenberg, Nilsa C. Ramirez, Jeremy Renkel, Mark Sherman, Lisa Wise, Peggy Yena, Erik Zmuda, Juliann Shih, Adrian Ally, Miruna Balasundaram, Rebecca Carlsen, Andy Chu, Eric Chuah, Amanda Clarke, Noreen Dhalla, Robert A. Holt, Steven J.M. Jones, Darlene Lee, Yussanne Ma, Marco A. Marra, Michael Mayo, Richard A. Moore, Andrew J. Mungall, Jacqueline E. Schein, Payal Sipahimalani, Angela Tam, Nina Thiessen, Kane Tse, Tina Wong, Denise Brooks, J. Todd Auman, Saianand Balu, Tom Bodenheimer, D. Neil Hayes, Alan P. Hoyle, Stuart R. Jefferys, Corbin D. Jones, Shaowu Meng, Piotr A. Mieczkowski, Lisle E. Mose, Charles M. Perou, Amy H. Perou, Jeffrey Roach, Yan Shi, Janae V. Simons, Tara Skelly, Matthew G. Soloway, Donghui Tan, Umadevi Veluvolu, Joel S. Parker, Matthew D. Wilkerson, Anil Korkut, Yasin Senbabaoglu, Patrick Burch, Robert McWilliams, Kari Chaffee, Ann Oberg, Wei Zhang, Marie-Claude Gingras, David A. Wheeler, Liu Xi, Monique Albert, John Bartlett, Harman Sekhon, Yeager Stephen, Zaren Howard, Miller Judy, Anne Breggia, Rachna T. Shroff, Sudha Chudamani, Jia Liu, Laxmi Lolla, Rashi Naresh, Todd Pihl, Qiang Sun, Yunhu Wan, Ye Wu, Smith Jennifer, Kevin Roggin, Karl-Friedrich Becker, Madhusmita Behera, Joseph Bennett, Lori Boice, Eric Burks, Carlos Gilberto Carlotti Junior, John Chabot, Daniela Pretti da Cunha Tirapelli, Jose Sebastião dos Santos, Michael Dubina, Jennifer Eschbacher, Mei Huang, Lori Huelsenbeck-Dill, Roger Jenkins, Alexey Karpov, Rafael Kemp, Vladimir Lyadov, Shishir Maithel, Georgy Manikhas, Eric Montgomery, Houtan Noushmehr, Adeboye Osunkoya, Taofeek Owonikoko, Oxana Paklina, Olga Potapova, Suresh Ramalingam, W. Kimryn Rathmell, Kimberly Rieger-Christ, Charles Saller, Galiya Setdikova, Alexey Shabunin, Gabriel Sica, Tao Su, Travis Sullivan, Pat Swanson, Katherine Tarvin, Michael Tavobilov, Leigh B. Thorne, Stefan Urbanski, Olga Voronina, Timothy Wang, Daniel Crain, Erin Curley, Johanna Gardner, David Mallery, Scott Morris, Joseph Paulauskis, Robert Penny, Candace Shelton, Troy Shelton, Klaus-Peter Janssen, Oliver Bathe, Nathan Bahary, Julia Slotta-Huspenina, Amber Johns, Hanina Hibshoosh, Rosa F. Hwang, Antonia Sepulveda, Amie Radenbaugh, Stephen B. Baylin, Mario Berrios, Moiz S. Bootwalla, Andrea Holbrook, Phillip H. Lai, Dennis T. Maglinte, Swapna Mahurkar, Timothy J. Triche, David J. Van Den Berg, Daniel J. Weisenberger, Lynda Chin, Raju Kucherlapati, Melanie Kucherlapati, Angeliki Pantazi, Peter Park, Doug Voet, Pei Lin, Scott Frazer, Timothy Defreitas, Sam Meier, Sun Young Kwon, Yong Hoon Kim, Sang-Jae Park, Sung-Sik Han, Seong Hoon Kim, Hark Kim, Emma Furth, Margaret Tempero, Chris Sander, Andrew Biankin, David Chang, Peter Bailey, Anthony Gill, James Kench, Sean Grimmond, Australian Pancreatic Cancer Genome Initiative (APGI, Russell Postier, Rosemary Zuna, Hugues Sicotte, John A. Demchok, Martin L. Ferguson, Carolyn M. Hutter, Kenna R. Mills Shaw, Margi Sheth, Heidi J. Sofia, Roy Tarnuzzer, Zhining Wang, Liming Yang, Jiashan (Julia) Zhang, Ina Felau, and Jean C. Zenklusen

Subjects
0301 basic medicine, Cancer Research, Proteome, endocrine system diseases, ARID1A, medicine.disease_cause, Article, Epigenesis, Genetic, PBRM1, Proto-Oncogene Proteins p21(ras), 03 medical and health sciences, CDKN2A, Pancreatic cancer, microRNA, medicine, GNAS complex locus, Humans, neoplasms, biology, Proteomic Profiling, Gene Expression Profiling, ADENOCARCINOMA, Genomics, Cell Biology, DNA Methylation, medicine.disease, digestive system diseases, 3. Good health, Gene Expression Regulation, Neoplastic, Pancreatic Neoplasms, 030104 developmental biology, Oncology, Mutation, Cancer research, biology.protein, KRAS, Transcriptome, Carcinoma, Pancreatic Ductal
Abstract

Summary We performed integrated genomic, transcriptomic, and proteomic profiling of 150 pancreatic ductal adenocarcinoma (PDAC) specimens, including samples with characteristic low neoplastic cellularity. Deep whole-exome sequencing revealed recurrent somatic mutations in KRAS , TP5 3, CDKN2A , SMAD4 , RNF43 , ARID1A , TGFβR2 , GNAS , RREB1 , and PBRM1 . KRAS wild-type tumors harbored alterations in other oncogenic drivers, including GNAS , BRAF , CTNNB1 , and additional RAS pathway genes. A subset of tumors harbored multiple KRAS mutations, with some showing evidence of biallelic mutations. Protein profiling identified a favorable prognosis subset with low epithelial-mesenchymal transition and high MTOR pathway scores. Associations of non-coding RNAs with tumor-specific mRNA subtypes were also identified. Our integrated multi-platform analysis reveals a complex molecular landscape of PDAC and provides a roadmap for precision medicine.

Published
2017

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