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133 results on '"Perez-Mancera, Pedro A."'

2. KrasP34R and KrasT58I mutations induce distinct RASopathy phenotypes in mice

Author

Wong, Jasmine C, Perez-Mancera, Pedro A, Huang, Tannie Q, Kim, Jangkyung, Grego-Bessa, Joaquim, del pilar Alzamora, Maria, Kogan, Scott C, Sharir, Amnon, Keefe, Susan H, Morales, Carolina E, Schanze, Denny, Castel, Pau, Hirose, Kentaro, Huang, Guo N, Zenker, Martin, Sheppard, Dean, Klein, Ophir, Tuveson, David, Braun, Benjamin S, and Shannon, Kevin

Subjects
Biomedical and Clinical Sciences, Pediatric, Lung, Cancer, Rare Diseases, Genetics, Aetiology, 2.1 Biological and endogenous factors, Animals, Cardiomyopathies, Craniosynostoses, Female, Hematologic Diseases, Lung Diseases, Male, Mice, Mice, Inbred C57BL, Mutation, Pregnancy, Proto-Oncogene Proteins p21(ras), Genetic diseases, Mouse models, Signal transduction, Biomedical and clinical sciences, Health sciences
Abstract

Somatic KRAS mutations are highly prevalent in many cancers. In addition, a distinct spectrum of germline KRAS mutations causes developmental disorders called RASopathies. The mutant proteins encoded by these germline KRAS mutations are less biochemically and functionally activated than those in cancer. We generated mice harboring conditional KrasLSL-P34Rand KrasLSL-T58I knock-in alleles and characterized the consequences of each mutation in vivo. Embryonic expression of KrasT58I resulted in craniofacial abnormalities reminiscent of those seen in RASopathy disorders, and these mice exhibited hyperplastic growth of multiple organs, modest alterations in cardiac valvulogenesis, myocardial hypertrophy, and myeloproliferation. By contrast, embryonic KrasP34R expression resulted in early perinatal lethality from respiratory failure due to defective lung sacculation, which was associated with aberrant ERK activity in lung epithelial cells. Somatic Mx1-Cre-mediated activation in the hematopoietic compartment showed that KrasP34R and KrasT58I expression had distinct signaling effects, despite causing a similar spectrum of hematologic diseases. These potentially novel strains are robust models for investigating the consequences of expressing endogenous levels of hyperactive K-Ras in different developing and adult tissues, for comparing how oncogenic and germline K-Ras proteins perturb signaling networks and cell fate decisions, and for performing preclinical therapeutic trials.

Published
2020

3. Mouse Models of Pancreatic Exocrine Cancer

Author

Pérez-Mancera, Pedro A., Urrutia, Raul, Section Editor, Büchler, M. W., Section Editor, Neoptolemos, John P., Section Editor, Hackert, Th., Section Editor, Neoptolemos, John P., editor, Urrutia, Raul, editor, Abbruzzese, James L., editor, and Büchler, Markus W., editor

Published
2018
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4. Figure S7 from Oncogenic KRAS Induces NIX-Mediated Mitophagy to Promote Pancreatic Cancer

Author

Humpton, Timothy J., primary, Alagesan, Brinda, primary, DeNicola, Gina M., primary, Lu, Dan, primary, Yordanov, Georgi N., primary, Leonhardt, Carl S., primary, Yao, Melissa A., primary, Alagesan, Priya, primary, Zaatari, Maya N., primary, Park, Youngkyu, primary, Skepper, Jeremy N., primary, Macleod, Kay F., primary, Perez-Mancera, Pedro A., primary, Murphy, Michael P., primary, Evan, Gerard I., primary, Vousden, Karen H., primary, and Tuveson, David A., primary

Published
2023
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5. Supplementary Table S12 from Tissue-Specific Oncogenic Activity of KRASA146T

Author

Poulin, Emily J., primary, Bera, Asim K., primary, Lu, Jia, primary, Lin, Yi-Jang, primary, Strasser, Samantha Dale, primary, Paulo, Joao A., primary, Huang, Tannie Q., primary, Morales, Carolina, primary, Yan, Wei, primary, Cook, Joshua, primary, Nowak, Jonathan A., primary, Brubaker, Douglas K., primary, Joughin, Brian A., primary, Johnson, Christian W., primary, DeStefanis, Rebecca A., primary, Ghazi, Phaedra C., primary, Gondi, Sudershan, primary, Wales, Thomas E., primary, Iacob, Roxana E., primary, Bogdanova, Lana, primary, Gierut, Jessica J., primary, Li, Yina, primary, Engen, John R., primary, Perez-Mancera, Pedro A., primary, Braun, Benjamin S., primary, Gygi, Steven P., primary, Lauffenburger, Douglas A., primary, Westover, Kenneth D., primary, and Haigis, Kevin M., primary

Published
2023
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6. Supplementary Tables S14-S17 from Tissue-Specific Oncogenic Activity of KRASA146T

Author

Poulin, Emily J., primary, Bera, Asim K., primary, Lu, Jia, primary, Lin, Yi-Jang, primary, Strasser, Samantha Dale, primary, Paulo, Joao A., primary, Huang, Tannie Q., primary, Morales, Carolina, primary, Yan, Wei, primary, Cook, Joshua, primary, Nowak, Jonathan A., primary, Brubaker, Douglas K., primary, Joughin, Brian A., primary, Johnson, Christian W., primary, DeStefanis, Rebecca A., primary, Ghazi, Phaedra C., primary, Gondi, Sudershan, primary, Wales, Thomas E., primary, Iacob, Roxana E., primary, Bogdanova, Lana, primary, Gierut, Jessica J., primary, Li, Yina, primary, Engen, John R., primary, Perez-Mancera, Pedro A., primary, Braun, Benjamin S., primary, Gygi, Steven P., primary, Lauffenburger, Douglas A., primary, Westover, Kenneth D., primary, and Haigis, Kevin M., primary

Published
2023
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7. Data from Oncogenic KRAS Induces NIX-Mediated Mitophagy to Promote Pancreatic Cancer

Author

Humpton, Timothy J., primary, Alagesan, Brinda, primary, DeNicola, Gina M., primary, Lu, Dan, primary, Yordanov, Georgi N., primary, Leonhardt, Carl S., primary, Yao, Melissa A., primary, Alagesan, Priya, primary, Zaatari, Maya N., primary, Park, Youngkyu, primary, Skepper, Jeremy N., primary, Macleod, Kay F., primary, Perez-Mancera, Pedro A., primary, Murphy, Michael P., primary, Evan, Gerard I., primary, Vousden, Karen H., primary, and Tuveson, David A., primary

Published
2023
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8. Data from Tissue-Specific Oncogenic Activity of KRASA146T

Author

Poulin, Emily J., primary, Bera, Asim K., primary, Lu, Jia, primary, Lin, Yi-Jang, primary, Strasser, Samantha Dale, primary, Paulo, Joao A., primary, Huang, Tannie Q., primary, Morales, Carolina, primary, Yan, Wei, primary, Cook, Joshua, primary, Nowak, Jonathan A., primary, Brubaker, Douglas K., primary, Joughin, Brian A., primary, Johnson, Christian W., primary, DeStefanis, Rebecca A., primary, Ghazi, Phaedra C., primary, Gondi, Sudershan, primary, Wales, Thomas E., primary, Iacob, Roxana E., primary, Bogdanova, Lana, primary, Gierut, Jessica J., primary, Li, Yina, primary, Engen, John R., primary, Perez-Mancera, Pedro A., primary, Braun, Benjamin S., primary, Gygi, Steven P., primary, Lauffenburger, Douglas A., primary, Westover, Kenneth D., primary, and Haigis, Kevin M., primary

Published
2023
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9. Supplementary Figures S1-S18 from Tissue-Specific Oncogenic Activity of KRASA146T

Author

Poulin, Emily J., primary, Bera, Asim K., primary, Lu, Jia, primary, Lin, Yi-Jang, primary, Strasser, Samantha Dale, primary, Paulo, Joao A., primary, Huang, Tannie Q., primary, Morales, Carolina, primary, Yan, Wei, primary, Cook, Joshua, primary, Nowak, Jonathan A., primary, Brubaker, Douglas K., primary, Joughin, Brian A., primary, Johnson, Christian W., primary, DeStefanis, Rebecca A., primary, Ghazi, Phaedra C., primary, Gondi, Sudershan, primary, Wales, Thomas E., primary, Iacob, Roxana E., primary, Bogdanova, Lana, primary, Gierut, Jessica J., primary, Li, Yina, primary, Engen, John R., primary, Perez-Mancera, Pedro A., primary, Braun, Benjamin S., primary, Gygi, Steven P., primary, Lauffenburger, Douglas A., primary, Westover, Kenneth D., primary, and Haigis, Kevin M., primary

Published
2023
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10. Supplementary Table 3 from Fibroblasts from Distinct Pancreatic Pathologies Exhibit Disease-Specific Properties

Author

Barrera, Lawrence N., primary, Evans, Anthony, primary, Lane, Brian, primary, Brumskill, Sarah, primary, Oldfield, Frances E., primary, Campbell, Fiona, primary, Andrews, Timothy, primary, Lu, Zipeng, primary, Perez-Mancera, Pedro A., primary, Liloglou, Triantafillos, primary, Ashworth, Milton, primary, Jalali, Mehdi, primary, Dawson, Rebecca, primary, Nunes, Quentin, primary, Phillips, Phoebe A., primary, Timms, John F., primary, Halloran, Christopher, primary, Greenhalf, William, primary, Neoptolemos, John P., primary, and Costello, Eithne, primary

Published
2023
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11. Supplementary Table 1 from Fibroblasts from Distinct Pancreatic Pathologies Exhibit Disease-Specific Properties

Author

Barrera, Lawrence N., primary, Evans, Anthony, primary, Lane, Brian, primary, Brumskill, Sarah, primary, Oldfield, Frances E., primary, Campbell, Fiona, primary, Andrews, Timothy, primary, Lu, Zipeng, primary, Perez-Mancera, Pedro A., primary, Liloglou, Triantafillos, primary, Ashworth, Milton, primary, Jalali, Mehdi, primary, Dawson, Rebecca, primary, Nunes, Quentin, primary, Phillips, Phoebe A., primary, Timms, John F., primary, Halloran, Christopher, primary, Greenhalf, William, primary, Neoptolemos, John P., primary, and Costello, Eithne, primary

Published
2023
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12. Supplementary Table 4 from Fibroblasts from Distinct Pancreatic Pathologies Exhibit Disease-Specific Properties

Author

Barrera, Lawrence N., primary, Evans, Anthony, primary, Lane, Brian, primary, Brumskill, Sarah, primary, Oldfield, Frances E., primary, Campbell, Fiona, primary, Andrews, Timothy, primary, Lu, Zipeng, primary, Perez-Mancera, Pedro A., primary, Liloglou, Triantafillos, primary, Ashworth, Milton, primary, Jalali, Mehdi, primary, Dawson, Rebecca, primary, Nunes, Quentin, primary, Phillips, Phoebe A., primary, Timms, John F., primary, Halloran, Christopher, primary, Greenhalf, William, primary, Neoptolemos, John P., primary, and Costello, Eithne, primary

Published
2023
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13. Data from Chemoresistance in Pancreatic Cancer Is Driven by Stroma-Derived Insulin-Like Growth Factors

Author

Ireland, Lucy, primary, Santos, Almudena, primary, Ahmed, Muhammad S., primary, Rainer, Carolyn, primary, Nielsen, Sebastian R., primary, Quaranta, Valeria, primary, Weyer-Czernilofsky, Ulrike, primary, Engle, Danielle D., primary, Perez-Mancera, Pedro A., primary, Coupland, Sarah E., primary, Taktak, Azzam, primary, Bogenrieder, Thomas, primary, Tuveson, David A., primary, Campbell, Fiona, primary, Schmid, Michael C., primary, and Mielgo, Ainhoa, primary

Published
2023
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14. Supplemental Methods from Fibroblasts from Distinct Pancreatic Pathologies Exhibit Disease-Specific Properties

Author

Barrera, Lawrence N., primary, Evans, Anthony, primary, Lane, Brian, primary, Brumskill, Sarah, primary, Oldfield, Frances E., primary, Campbell, Fiona, primary, Andrews, Timothy, primary, Lu, Zipeng, primary, Perez-Mancera, Pedro A., primary, Liloglou, Triantafillos, primary, Ashworth, Milton, primary, Jalali, Mehdi, primary, Dawson, Rebecca, primary, Nunes, Quentin, primary, Phillips, Phoebe A., primary, Timms, John F., primary, Halloran, Christopher, primary, Greenhalf, William, primary, Neoptolemos, John P., primary, and Costello, Eithne, primary

Published
2023
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15. Supplementary Figure Legends, Supplementary Tables 1 and 2 and Supplementary Materials and Methods from Chemoresistance in Pancreatic Cancer Is Driven by Stroma-Derived Insulin-Like Growth Factors

Author

Ireland, Lucy, primary, Santos, Almudena, primary, Ahmed, Muhammad S., primary, Rainer, Carolyn, primary, Nielsen, Sebastian R., primary, Quaranta, Valeria, primary, Weyer-Czernilofsky, Ulrike, primary, Engle, Danielle D., primary, Perez-Mancera, Pedro A., primary, Coupland, Sarah E., primary, Taktak, Azzam, primary, Bogenrieder, Thomas, primary, Tuveson, David A., primary, Campbell, Fiona, primary, Schmid, Michael C., primary, and Mielgo, Ainhoa, primary

Published
2023
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16. Supplementary Figures 1 through 9 from Chemoresistance in Pancreatic Cancer Is Driven by Stroma-Derived Insulin-Like Growth Factors

Author

Ireland, Lucy, primary, Santos, Almudena, primary, Ahmed, Muhammad S., primary, Rainer, Carolyn, primary, Nielsen, Sebastian R., primary, Quaranta, Valeria, primary, Weyer-Czernilofsky, Ulrike, primary, Engle, Danielle D., primary, Perez-Mancera, Pedro A., primary, Coupland, Sarah E., primary, Taktak, Azzam, primary, Bogenrieder, Thomas, primary, Tuveson, David A., primary, Campbell, Fiona, primary, Schmid, Michael C., primary, and Mielgo, Ainhoa, primary

Published
2023
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17. Data from Fibroblasts from Distinct Pancreatic Pathologies Exhibit Disease-Specific Properties

Author

Barrera, Lawrence N., primary, Evans, Anthony, primary, Lane, Brian, primary, Brumskill, Sarah, primary, Oldfield, Frances E., primary, Campbell, Fiona, primary, Andrews, Timothy, primary, Lu, Zipeng, primary, Perez-Mancera, Pedro A., primary, Liloglou, Triantafillos, primary, Ashworth, Milton, primary, Jalali, Mehdi, primary, Dawson, Rebecca, primary, Nunes, Quentin, primary, Phillips, Phoebe A., primary, Timms, John F., primary, Halloran, Christopher, primary, Greenhalf, William, primary, Neoptolemos, John P., primary, and Costello, Eithne, primary

Published
2023
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18. Supplementary Table 2 from Fibroblasts from Distinct Pancreatic Pathologies Exhibit Disease-Specific Properties

Author

Barrera, Lawrence N., primary, Evans, Anthony, primary, Lane, Brian, primary, Brumskill, Sarah, primary, Oldfield, Frances E., primary, Campbell, Fiona, primary, Andrews, Timothy, primary, Lu, Zipeng, primary, Perez-Mancera, Pedro A., primary, Liloglou, Triantafillos, primary, Ashworth, Milton, primary, Jalali, Mehdi, primary, Dawson, Rebecca, primary, Nunes, Quentin, primary, Phillips, Phoebe A., primary, Timms, John F., primary, Halloran, Christopher, primary, Greenhalf, William, primary, Neoptolemos, John P., primary, and Costello, Eithne, primary

Published
2023
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19. Supplementary Figure 1 from Fibroblasts from Distinct Pancreatic Pathologies Exhibit Disease-Specific Properties

Author

Barrera, Lawrence N., primary, Evans, Anthony, primary, Lane, Brian, primary, Brumskill, Sarah, primary, Oldfield, Frances E., primary, Campbell, Fiona, primary, Andrews, Timothy, primary, Lu, Zipeng, primary, Perez-Mancera, Pedro A., primary, Liloglou, Triantafillos, primary, Ashworth, Milton, primary, Jalali, Mehdi, primary, Dawson, Rebecca, primary, Nunes, Quentin, primary, Phillips, Phoebe A., primary, Timms, John F., primary, Halloran, Christopher, primary, Greenhalf, William, primary, Neoptolemos, John P., primary, and Costello, Eithne, primary

Published
2023
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20. Supplementary Figure 2 from Fibroblasts from Distinct Pancreatic Pathologies Exhibit Disease-Specific Properties

Author

Barrera, Lawrence N., primary, Evans, Anthony, primary, Lane, Brian, primary, Brumskill, Sarah, primary, Oldfield, Frances E., primary, Campbell, Fiona, primary, Andrews, Timothy, primary, Lu, Zipeng, primary, Perez-Mancera, Pedro A., primary, Liloglou, Triantafillos, primary, Ashworth, Milton, primary, Jalali, Mehdi, primary, Dawson, Rebecca, primary, Nunes, Quentin, primary, Phillips, Phoebe A., primary, Timms, John F., primary, Halloran, Christopher, primary, Greenhalf, William, primary, Neoptolemos, John P., primary, and Costello, Eithne, primary

Published
2023
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22. Abstract C084: Oncogenic KRAS signaling drives the activation of tissue-resident fibroblasts and is required to maintain CAF heterogeneity in pancreatic cancer

Author

Caligiuri, Giuseppina, primary, Thalappillil, Jennifer S., additional, Shakiba, Mojdeh, additional, Nadella, Sandeep, additional, Hinds, Juliene, additional, Courtois, Elise, additional, Flynn, William F., additional, Alagesan, Brinda, additional, Yordanov, Georgi N., additional, Kaminow, Benjamin, additional, Robson, Paul, additional, Perez-Mancera, Pedro A., additional, Preall, Jonathan, additional, Dobin, Alexander, additional, Park, Youngku, additional, and Tuveson, David A., additional

Published
2022
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25. Abstract 3647: Oncogenic Kras drives cancer-associated fibroblast heterogeneity and substate changes in pancreatic cancer

Author

Thalappillil, Jennifer S., primary, Caligiuri, Giuseppina, additional, Nadella, Sandeep, additional, Alagesan, Brinda, additional, Yordanov, Georgi N., additional, Shakiba, Mojdeh, additional, Kaminow, Benjamin, additional, Hinds, Juliene, additional, Perez-Mancera, Pedro A., additional, Preall, Jonathan, additional, Dobin, Alexander, additional, Park, Youngkyu, additional, and Tuveson, David A., additional

Published
2022
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27. The deubiquitinase USP9X suppresses pancreatic ductal adenocarcinoma

Author

Perez-Mancera, Pedro A., Rust, Alistair G., van der Weyden, Louise, Kristiansen, Glen, Li, Allen, Sarver, Aaron L., Silverstein, Kevin A.T., Grutzmann, Robert, Aust, Daniela, Rummele, Petra, Knosel, Thomas, Herd, Colin, Stemple, Derek L., Kettleborough, Ross, Brosnan, Jacqueline A., Li, Ang, Morgan, Richard, Knight, Spencer, Yu, Jun, Stegeman, Shane, Collier, Lara S., ten Hoeve, Jelle J., de Ridder, Jeroen, Klein, Alison P., Goggins, Michael, Hruban, Ralph H., Chang, David K., Biankin, Andrew V., Grimmond, Sean M., Wessels, Lodewyk F.A., Wood, Stephen A., Iacobuzio-Donahue, Christine A., Pilarsky, Christian, Largaespada, David A., Adams, David J., and Tuveson, David A.

Subjects
Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Pancreatic ductal adenocarcinoma (PDA) remains a lethal malignancy despite much progress concerning its molecular characterization. PDA tumours harbour four signature somatic mutations (1-4) in addition to numerous lower frequency genetic events of uncertain significance (5). Here we use Sleeping Beauty (SB) transposon-mediated insertional mutagenesis (6,7) in a mouse model of pancreatic ductal preneoplasia (8) to identify genes that cooperate with oncogenic [Kras.sup.G12D] to accelerate tumorigenesis and promote progression. Our screen revealed new candidate genes for PDA and confirmed the importance of many genes and pathways previously implicated in human PDA. The most commonly mutated gene was the X-linked deubiquitinase Usp9x, which was inactivated in over 50% of the tumours. Although previous work had attributed a pro-survival role to USP9X in human neoplasia (9), we found instead that loss of Usp9x enhances transformation and protects pancreatic cancer cells from anoikis. Clinically, low USP9X protein and messenger RNA expression in PDA correlates with poor survival after surgery, and USP9X levels are inversely associated with metastatic burden in advanced disease. Furthermore, chromatin modulation with trichostatin A or 5-aza-2'-deoxycytidine elevates USP9X expression in human PDA cell lines, indicating a clinical approach for certain patients. The conditional deletion of Usp9x cooperated with [Kras.sup.G12D] to accelerate pancreatic tumorigenesis in mice, validating their genetic interaction. We propose that USP9X is a major tumour suppressor gene with prognostic and therapeutic relevance in PDA., The biological sequelae of PDA has been partially attributed to frequent and well characterized mutations in KRAS (>90%), CDKN2A (>90%), TP53 (70%) and SMAD4 (55%) (1-4). Recent genomewide analyses have [...]

Published
2012
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30. A novel scaffold based hybrid multicellular model for pancreatic ductal adenocarcinoma – towards a better mimicry of the in vivo tumour microenvironment

Author

Gupta, Priyanka, Perez-Mancera, Pedro A., Kocher, Hemant, Nisbet, Andrew, Schettino, Giuseppe, and Velliou, Eirini

Abstract

With a very low survival rate, pancreatic ductal adenocarcinoma (PDAC) is a deadly disease. This has been primarily attributed to – (i) its late diagnosis and (ii) its high resistance to current treatment methods. The later, specifically requires the development of robust, realistic in vitro models of PDAC, capable of accurately mimicking the in vivo tumour niche. Advancements in the field of Tissue Engineering (TE) have helped the development of such models for PDAC. Herein, we report for the first time a novel hybrid, poly- urethane (PU) scaffold based, long term, multicellular (tri-culture) model of pancreatic cancer involving cancer cells, endothelial cells and stellate cells. Recognising the importance of ECM proteins for optimal growth of different cell types, the model consists of two different zones/compartments: an inner tumour compartment consisting of cancer cells (fibronectin coated) and a surrounding stromal compartment consisting of stellate and endothelial cells (collagen I coated). Our developed novel hybrid, tri-culture model supports the proliferation of all different cell types for 35 days (5 weeks), which is the longest reported time frame in vitro. Furthermore, the hybrid model showed extensive collagen I production by the cells, mimicking desmoplasia, one of PDAC’s hallmark features. Fibril alignment of the stellate cells was observed, which attested for their activated state. All three cell types expressed various cell specific markers within the scaffolds, throughout the culture period and showed cellular migration between the two zones of the hybrid scaffold. Our novel model has great potential as a low cost tool for in vitro studies of PDAC as well as for treatment screening.

Published
2020

31. Acute mutation of retinoblastoma gene function is sufficient for cell cycle re-entry

Author

Sage, Julien, Miller, Abigail L., Perez-Mancera, Pedro A., Wysocki, Julianne M., and Jacks, Tyler

Subjects
Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Author(s): Julien Sage [1]; Abigail L. Miller [1]; Pedro A. Pérez-Mancera [3]; Julianne M. Wysocki [1]; Tyler Jacks (corresponding author) [1, 2] Cancer cells arise from normal cells through the [...]

Published
2003
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32. Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes

Author

Biankin, Andrew V., Waddell, Nicola, Kassahn, Karin S., Gingras, Marie-Claude, Muthuswamy, Lakshmi B., Johns, Amber L., Miller, David K., Wilson, Peter J., Patch, Ann-Marie, Wu, Jianmin, Chang, David K., Cowley, Mark J., Gardiner, Brooke B., Song, Sarah, Harliwong, Ivon, Idrisoglu, Senel, Nourse, Craig, Nourbakhsh, Ehsan, Manning, Suzanne, Wani, Shivangi, Gongora, Milena, Pajic, Marina, Scarlett, Christopher J., Gill, Anthony J., Pinho, Andreia V., Rooman, Ilse, Anderson, Matthew, Holmes, Oliver, Leonard, Conrad, Taylor, Darrin, Wood, Scott, Xu, Qinying, Nones, Katia, Lynn Fink, J., Christ, Angelika, Bruxner, Tim, Cloonan, Nicole, Kolle, Gabriel, Newell, Felicity, Pinese, Mark, Scott Mead, R., Humphris, Jeremy L., Kaplan, Warren, Jones, Marc D., Colvin, Emily K., Nagrial, Adnan M., Humphrey, Emily S., Chou, Angela, Chin, Venessa T., Chantrill, Lorraine A., Mawson, Amanda, Samra, Jaswinder S., Kench, James G., Lovell, Jessica A., Daly, Roger J., Merrett, Neil D., Toon, Christopher, Epari, Krishna, Nguyen, Nam Q., Barbour, Andrew, Zeps, Nikolajs, Brancato, Mary-Anne L., Rowe, Sarah J., Simpson, Skye L., Martyn-Smith, Mona, Thomas, Michelle T., Pettit, Jessica, Tao, Jiang, DiPietro, Renee, Watson, Clare, Wong, Rachel, Giry-Laterriere, Marc, Pavlakis, Nick, Guminski, Alex, Asghari, Ray, Pavey, Darren A., Das, Amitabha, Cosman, Peter H., Ismail, Kasim, O’Connor, Chelsie, Lam, Vincent W., McLeod, Duncan, Pleass, Henry C., Richardson, Arthur, James, Virginia, Cooper, Caroline L., Joseph, David, Sandroussi, Charbel, Crawford, Michael, Gallagher, James, Texler, Michael, Forrest, Cindy, Laycock, Andrew, Epari, Krishna P., Ballal, Mo, Fletcher, David R., Mukhedkar, Sanjay, Spry, Nigel A., DeBoer, Bastiaan, Chai, Ming, Beilin, Maria, Feeney, Kynan, Ruszkiewicz, Andrew R., Worthley, Chris, Tan, Chuan P., Debrencini, Tamara, Chen, John, Brooke-Smith, Mark E., Papangelis, Virginia, Tang, Henry, Barbour, Andrew P., Clouston, Andrew D., Martin, Patrick, O’Rourke, Thomas J., Chiang, Amy, Fawcett, Jonathan W., Slater, Kellee, Yeung, Shinn, Hatzifotis, Michael, Hodgkinson, Peter, Christophi, Christopher, Nikfarjam, Mehrdad, Mountain Victorian Cancer Biobank, Angela, Eshleman, James R., Schulick, Richard D., Wolfgang, Christopher L., Morgan, Richard A., Hodgin, Mary B., Lawlor, Rita T., Capelli, Paola, Beghelli, Stefania, Corbo, Vincenzo, Scardoni, Maria, Pederzoli, Paolo, Tortora, Giampaolo, Bassi, Claudio, Kakkar, Nipun, Zhao, Fengmei, Qing Wu, Yuan, Wang, Min, Muzny, Donna M., Fisher, William E., Charles Brunicardi, F., Hodges, Sally E., Reid, Jeffrey G., Drummond, Jennifer, Chang, Kyle, Han, Yi, Lewis, Lora R., Dinh, Huyen, Buhay, Christian J., Beck, Timothy, Timms, Lee, Sam, Michelle, Begley, Kimberly, Brown, Andrew, Pai, Deepa, Panchal, Ami, Buchner, Nicholas, De Borja, Richard, Denroche, Robert E., Yung, Christina K., Serra, Stefano, Onetto, Nicole, Mukhopadhyay, Debabrata, Tsao, Ming-Sound, Shaw, Patricia A., Petersen, Gloria M., Gallinger, Steven, Hruban, Ralph H., Maitra, Anirban, Iacobuzio-Donahue, Christine A., Tempero, Margaret A., Mann, Karen M., Jenkins, Nancy A., Perez-Mancera, Pedro A., Adams, David J., Largaespada, David A., Wessels, Lodewyk F. A., Rust, Alistair G., Stein, Lincoln D., Tuveson, David A., Copeland, Neal G., Musgrove, Elizabeth A., Scarpa, Aldo, Hudson, Thomas J., Sutherland, Robert L., Wheeler, David A., Pearson, John V., McPherson, John D., Gibbs, Richard A., and Grimmond, Sean M.

Published
2012
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34. ZNF703 is a common Luminal B breast cancer oncogene that differentially regulates luminal and basal progenitors in human mammary epithelium

Author

Holland, Daniel G., Burleigh, Angela, Git, Anna, Goldgraben, Mae A., Perez-Mancera, Pedro A., Chin, Suet-Feung, Hurtado, Antonio, Bruna, Alejandra, Ali, Raza H., Greenwood, Wendy, Dunning, Mark J., Samarajiwa, Shamith, Menon, Suraj, Rueda, Oscar M., Lynch, Andy G., McKinney, Steven, Ellis, Ian O., Eaves, Connie J., Carroll, Jason S., Curtis, Christina, Aparicio, Samuel, and Caldas, Carlos

Published
2011
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35. Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma

Author

Varela, Ignacio, Tarpey, Patrick, Raine, Keiran, Huang, Dachuan, Ong, Choon Kiat, Stephens, Philip, Davies, Helen, Jones, David, Lin, Meng-Lay, Teague, Jon, Bignell, Graham, Butler, Adam, Cho, Juok, Dalgliesh, Gillian L., Galappaththige, Danushka, Greenman, Chris, Hardy, Claire, Jia, Mingming, Latimer, Calli, Lau, King Wai, Marshall, John, McLaren, Stuart, Menzies, Andrew, Mudie, Laura, Stebbings, Lucy, Largaespada, David A., Wessels, L. F. A., Richard, Stephane, Kahnoski, Richard J., Anema, John, Tuveson, David A., Perez-Mancera, Pedro A., Mustonen, Ville, Fischer, Andrej, Adams, David J., Rust, Alistair, Chan-on, Waraporn, Subimerb, Chutima, Dykema, Karl, Furge, Kyle, Campbell, Peter J., Teh, Bin Tean, Stratton, Michael R., and Futreal, Andrew P.

Published
2011
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36. Fibroblasts from Distinct Pancreatic Pathologies Exhibit Disease-Specific Properties

Author

Barrera, Lawrence N., primary, Evans, Anthony, additional, Lane, Brian, additional, Brumskill, Sarah, additional, Oldfield, Frances E., additional, Campbell, Fiona, additional, Andrews, Timothy, additional, Lu, Zipeng, additional, Perez-Mancera, Pedro A., additional, Liloglou, Triantafillos, additional, Ashworth, Milton, additional, Jalali, Mehdi, additional, Dawson, Rebecca, additional, Nunes, Quentin, additional, Phillips, Phoebe A., additional, Timms, John F., additional, Halloran, Christopher, additional, Greenhalf, William, additional, Neoptolemos, John P., additional, and Costello, Eithne, additional

Published
2020
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38. Oncogenic KRAS Induces NIX-Mediated Mitophagy to Promote Pancreatic Cancer

Author

Humpton, Timothy J., primary, Alagesan, Brinda, additional, DeNicola, Gina M., additional, Lu, Dan, additional, Yordanov, Georgi N., additional, Leonhardt, Carl S., additional, Yao, Melissa A., additional, Alagesan, Priya, additional, Zaatari, Maya N., additional, Park, Youngkyu, additional, Skepper, Jeremy N., additional, Macleod, Kay F., additional, Perez-Mancera, Pedro A., additional, Murphy, Michael P., additional, Evan, Gerard I., additional, Vousden, Karen H., additional, and Tuveson, David A., additional

Published
2019
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39. PDAC-associated fibroblasts are less responsive to an anti-fibrotic stimulus and more responsive to a positive regulator of fibroblast activation than normal activated fibroblasts

Author

Barrera, Lawrence N., primary, Evans, Anthony, additional, Lane, Brian, additional, Brumskill, Sarah, additional, Oldfield, Frances, additional, Campbell, Fioana, additional, Andrews, Timothy, additional, Lu, Zipeng, additional, Perez-Mancera, Pedro A., additional, Liloglou, Triantafillos, additional, Jalali, Mehdi, additional, Dawson, Rebecca, additional, Nunes, Quentin, additional, Phillips, Phoebe, additional, Timms, John F., additional, Menon, Usha, additional, Halloran, Christopher, additional, Greenhalf, William, additional, Neoptolemos, John P., additional, and Costello, Eithne, additional

Published
2019
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40. Tissue-Specific Oncogenic Activity of KRASA146T

Author

Poulin, Emily J., primary, Bera, Asim K., additional, Lu, Jia, additional, Lin, Yi-Jang, additional, Strasser, Samantha Dale, additional, Paulo, Joao A., additional, Huang, Tannie Q., additional, Morales, Carolina, additional, Yan, Wei, additional, Cook, Joshua, additional, Nowak, Jonathan A., additional, Brubaker, Douglas K., additional, Joughin, Brian A., additional, Johnson, Christian W., additional, DeStefanis, Rebecca A., additional, Ghazi, Phaedra C., additional, Gondi, Sudershan, additional, Wales, Thomas E., additional, Iacob, Roxana E., additional, Bogdanova, Lana, additional, Gierut, Jessica J., additional, Li, Yina, additional, Engen, John R., additional, Perez-Mancera, Pedro A., additional, Braun, Benjamin S., additional, Gygi, Steven P., additional, Lauffenburger, Douglas A., additional, Westover, Kenneth D., additional, and Haigis, Kevin M., additional

Published
2019
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41. Chemoresistance in Pancreatic Cancer Is Driven by Stroma-Derived Insulin-Like Growth Factors

Author

Ireland, Lucy, Santos, Almudena, Ahmed, Muhammad S., Rainer, Carolyn, Nielsen, Sebastian R., Quaranta, Valeria, Weyer-Czernilofsky, Ulrike, Engle, Danielle D., Perez-Mancera, Pedro A., Coupland, Sarah E., Taktak, Azzam, Bogenrieder, Thomas, Tuveson, David A., Campbell, Fiona, Schmid, Michael C., and Mielgo, Ainhoa

Subjects
Pancreatic Neoplasms, Mice, Somatomedins, Cell Line, Tumor, Animals, Humans, Article, Cell Proliferation, Signal Transduction
Abstract

Tumor-associated macrophages (TAM) and myofibroblasts are key drivers in cancer that are associated with drug resistance in many cancers, including pancreatic ductal adenocarcinoma (PDAC). However, our understanding of the molecular mechanisms by which TAM and fibroblasts contribute to chemoresistance is unclear. In this study, we found that TAM and myofibroblasts directly support chemoresistance of pancreatic cancer cells by secreting insulin-like growth factors (IGF) 1 and 2, which activate insulin/IGF receptors on pancreatic cancer cells. Immunohistochemical analysis of biopsies from patients with pancreatic cancer revealed that 72% of the patients expressed activated insulin/IGF receptors on tumor cells, and this positively correlates with increased CD163+ TAM infiltration. In vivo, we found that TAM and myofibroblasts were the main sources of IGF production, and pharmacologic blockade of IGF sensitized pancreatic tumors to gemcitabine. These findings suggest that inhibition of IGF in combination with chemotherapy could benefit patients with PDAC, and that insulin/IGF1R activation may be used as a biomarker to identify patients for such therapeutic intervention.

Published
2016

42. Disease associated fibroblasts from various pancreatic disorders exhibit subtype specific genetic profile

Author

Barrera, Lawrence, primary, Evans, Anthony, additional, Lane, Brian, additional, Brumskill, Sarah, additional, Oldfield, Frances, additional, Campbell, Fioana, additional, Andrews, Timothy, additional, Perez-Mancera, Pedro, additional, Liloglou, Triantafillos, additional, Phillips, Phoebe, additional, Halloran, Christopher, additional, Greenhalf, William, additional, Neoptolemos, John P., additional, and Costello, Eithne, additional

Published
2018
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45. Chemoresistance in Pancreatic Cancer Is Driven by Stroma-Derived Insulin-Like Growth Factors

Author

Ireland, Lucy, primary, Santos, Almudena, additional, Ahmed, Muhammad S., additional, Rainer, Carolyn, additional, Nielsen, Sebastian R., additional, Quaranta, Valeria, additional, Weyer-Czernilofsky, Ulrike, additional, Engle, Danielle D., additional, Perez-Mancera, Pedro A., additional, Coupland, Sarah E., additional, Taktak, Azzam, additional, Bogenrieder, Thomas, additional, Tuveson, David A., additional, Campbell, Fiona, additional, Schmid, Michael C., additional, and Mielgo, Ainhoa, additional

Published
2016
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46. Identification of novel signalling pathways dysregulated in pancreatic cancer-associated fibroblasts

Author

Barrera, Lawrence, primary, Lane, Brian, additional, Brumskill, Sarah, additional, Oldfield, Frances, additional, Lamond, Rebecca, additional, Wilkinson, Luke, additional, Bermejo-Rodriguez, Camino, additional, Aughton, Karen, additional, Sanna, Roberta, additional, Nunes, Quentin, additional, Perez-Mancera, Pedro, additional, Campbell, Fiona, additional, Andrews, Timothy, additional, Phillips, Phoebe, additional, Halloran, Christopher, additional, Sutton, Robert, additional, Greenhalf, William, additional, Neoptolemos, John, additional, and Costello, Eithne, additional

Published
2016
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47. Abstract 798: Clonal analysis and clinical translation of pancreatic adenocarcinoma genomes.

Author

Barrett, Michael T., primary, Lenkiewicz, Elizabeth, additional, Lisa, Evers, additional, Perez-Mancera, Pedro, additional, Tuveson, David, additional, Aust, Daniela, additional, Pilarsky, Christian, additional, Aziz, Meraj, additional, Posner, Richard, additional, Ramanathan, Ramesh, additional, Velculescu, Victor, additional, Kramer, Amy, additional, Drebin, Jeffrey, additional, and Von Hoff, Daniel D., additional

Published
2013
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50. Erratum: Corrigendum: Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma

Author

Varela, Ignacio, primary, Tarpey, Patrick, additional, Raine, Keiran, additional, Huang, Dachuan, additional, Ong, Choon Kiat, additional, Stephens, Philip, additional, Davies, Helen, additional, Jones, David, additional, Lin, Meng-Lay, additional, Teague, Jon, additional, Bignell, Graham, additional, Butler, Adam, additional, Cho, Juok, additional, Dalgliesh, Gillian L., additional, Galappaththige, Danushka, additional, Greenman, Chris, additional, Hardy, Claire, additional, Jia, Mingming, additional, Latimer, Calli, additional, Lau, KingWai, additional, Marshall, John, additional, McLaren, Stuart, additional, Menzies, Andrew, additional, Mudie, Laura, additional, Stebbings, Lucy, additional, Largaespada, David A., additional, A.Wessels, L. F., additional, Richard, Stephane, additional, J.Kahnoski, Richard, additional, Anema, John, additional, A.Tuveson, David, additional, Perez-Mancera, Pedro A., additional, Mustonen, Ville, additional, Fischer, Andrej, additional, Adams, David J., additional, Rust, Alistair, additional, Chan-on, Waraporn, additional, Subimerb, Chutima, additional, Dykema, Karl, additional, Furge, Kyle, additional, Campbell, Peter J., additional, Teh, Bin Tean, additional, Stratton, Michael R., additional, and Futreal, P. Andrew, additional

Published
2012
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