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17 results on '"Colom, Bartomeu"'

1. Organismal metabolism regulates the expansion of oncogenic PIK3CA mutant clones in normal esophagus

Author

Herms, Albert, Colom, Bartomeu, Piedrafita, Gabriel, Kalogeropoulou, Argyro, Banerjee, Ujjwal, King, Charlotte, Abby, Emilie, Murai, Kasumi, Caseda, Irene, Fernandez-Antoran, David, Ong, Swee Hoe, Hall, Michael W. J., Bryant, Christopher, Sood, Roshan K., Fowler, Joanna C., Pol, Albert, Frezza, Christian, Vanhaesebroeck, Bart, and Jones, Philip H.

Published
2024
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2. Self-sustaining long-term 3D epithelioid cultures reveal drivers of clonal expansion in esophageal epithelium

Author

Herms, Albert, Fernandez-Antoran, David, Alcolea, Maria P., Kalogeropoulou, Argyro, Banerjee, Ujjwal, Piedrafita, Gabriel, Abby, Emilie, Valverde-Lopez, Jose Antonio, Ferreira, Inês S., Caseda, Irene, Bejar, Maria T., Dentro, Stefan C., Vidal-Notari, Sara, Ong, Swee Hoe, Colom, Bartomeu, Murai, Kasumi, King, Charlotte, Mahbubani, Krishnaa, Saeb-Parsy, Kourosh, Lowe, Alan R., Gerstung, Moritz, and Jones, Philip H.

Published
2024
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3. Organismal metabolism regulates the expansion of oncogenic PIK3CAmutant clones in normal esophagus

Author

Herms, Albert, Colom, Bartomeu, Piedrafita, Gabriel, Kalogeropoulou, Argyro, Banerjee, Ujjwal, King, Charlotte, Abby, Emilie, Murai, Kasumi, Caseda, Irene, Fernandez-Antoran, David, Ong, Swee Hoe, Hall, Michael W. J., Bryant, Christopher, Sood, Roshan K., Fowler, Joanna C., Pol, Albert, Frezza, Christian, Vanhaesebroeck, Bart, and Jones, Philip H.

Abstract

Oncogenic PIK3CAmutations generate large clones in aging human esophagus. Here we investigate the behavior of Pik3camutant clones in the normal esophageal epithelium of transgenic mice. Expression of a heterozygous Pik3caH1047Rmutation drives clonal expansion by tilting cell fate toward proliferation. CRISPR screening and inhibitor treatment of primary esophageal keratinocytes confirmed the PI3K–mTOR pathway increased mutant cell competitive fitness. The antidiabetic drug metformin reduced mutant cell advantage in vivo and in vitro. Conversely, metabolic conditions such as type 1 diabetes or diet-induced obesity enhanced the competitive fitness of Pik3caH1047Rcells. Consistently, we found a higher density of PIK3CAgain-of-function mutations in the esophagus of individuals with high body mass index compared with those with normal weight. We conclude that the metabolic environment selectively influences the evolution of the normal epithelial mutational landscape. Clinically feasible interventions to even out signaling imbalances between wild-type and mutant cells may limit the expansion of oncogenic mutants in normal tissues.

Published
2024
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6. Epithelioids: Self-sustaining 3D epithelial cultures to study long-term processes

Author

Herms, Albert, primary, Fernandez-Antoran, David, additional, Alcolea, Maria P., additional, Kalogeropoulou, Argyro, additional, Banerjee, Ujjwal, additional, Piedrafita, Gabriel, additional, Abby, Emilie, additional, Valverde-Lopez, Jose Antonio, additional, Ferreira, Inês S., additional, Dentro, Stefan C., additional, Ong, Swee Hoe, additional, Colom, Bartomeu, additional, Murai, Kasumi, additional, King, Charlotte, additional, Mahbubani, Krishnaa, additional, Saeb-Parsy, Kourosh, additional, Lowe, Alan R, additional, Gerstung, Moritz, additional, and Jones, Philip H, additional

Published
2023
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8. Spatial competition shapes the dynamic mutational landscape of normal esophageal epithelium

Author

Colom, Bartomeu, Alcolea, Maria P, Piedrafita, Gabriel, Hall, Michael WJ, Wabik, Agnieszka, Dentro, Stefan C, Fowler, Joanna C, Herms, Albert, King, Charlotte, Ong, Swee Hoe, Sood, Roshan K, Gerstung, Moritz, Martincorena, Inigo, Hall, Benjamin A, Jones, Philip H, Colom, Bartomeu [0000-0001-6256-6462], Piedrafita, Gabriel [0000-0001-8701-1084], Ong, Swee Hoe [0000-0002-3629-5387], Sood, Roshan K [0000-0002-1318-7025], Gerstung, Moritz [0000-0001-6709-963X], Hall, Benjamin A [0000-0003-0355-2946], Jones, Philip H [0000-0002-5904-795X], and Apollo - University of Cambridge Repository

Subjects
Male, High-Throughput Nucleotide Sequencing, Membrane Proteins, Reproducibility of Results, Mice, Transgenic, Epithelium, Mice, Inbred C57BL, ADAM10 Protein, Esophagus, Mutation, Animals, Cell Lineage, Diethylnitrosamine, Female, Receptor, Notch2, Amyloid Precursor Protein Secretases, Receptor, Notch1, Tumor Suppressor Protein p53, health care economics and organizations
Abstract

During aging, progenitor cells acquire mutations, which may generate clones that colonize the surrounding tissue. By middle age, normal human tissues, including the esophageal epithelium (EE), become a patchwork of mutant clones. Despite their relevance for understanding aging and cancer, the processes that underpin mutational selection in normal tissues remain poorly understood. Here, we investigated this issue in the esophageal epithelium of mutagen-treated mice. Deep sequencing identified numerous mutant clones with multiple genes under positive selection, including Notch1, Notch2 and Trp53, which are also selected in human esophageal epithelium. Transgenic lineage tracing revealed strong clonal competition that evolved over time. Clone dynamics were consistent with a simple model in which the proliferative advantage conferred by positively selected mutations depends on the nature of the neighboring cells. When clones with similar competitive fitness collide, mutant cell fate reverts towards homeostasis, a constraint that explains how selection operates in normal-appearing epithelium.

Published
2020

10. Levelling out differences in aerobic glycolysis neutralizes the competitive advantage of oncogenicPIK3CAmutant progenitors in the esophagus

Author

Herms, Albert, primary, Colom, Bartomeu, additional, Piedrafita, Gabriel, additional, Murai, Kasumi, additional, Ong, Swee Hoe, additional, Fernandez-Antoran, David, additional, Bryant, Christopher, additional, Frezza, Christian, additional, Vanhaesebroeck, Bart, additional, and Jones, Philip H., additional

Published
2021
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12. Spatial competition shapes the dynamic mutational landscape of normal esophageal epithelium

Author

Colom, Bartomeu, primary, Alcolea, Maria P., additional, Piedrafita, Gabriel, additional, Hall, Michael W. J., additional, Wabik, Agnieszka, additional, Dentro, Stefan C., additional, Fowler, Joanna C., additional, Herms, Albert, additional, King, Charlotte, additional, Ong, Swee Hoe, additional, Sood, Roshan K., additional, Gerstung, Moritz, additional, Martincorena, Inigo, additional, Hall, Benjamin A., additional, and Jones, Philip H., additional

Published
2020
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17. Sexual Dimorphism in the Alterations of Cardiac Muscle Mitochondrial Bioenergetics Associated to the Ageing Process.

Author

Colom, Bartomeu, Oliver, Jordi, and Garcia-Palmer, Francisco J.

Subjects
*BIOENERGETICS, *SEXUAL dimorphism, *AGE factors in disease, *MYOCARDIUM physiology, *HEART failure, *MITOCHONDRIAL physiology, *PROTEIN metabolism, *ENZYME metabolism, *ADENOSINE triphosphatase, *AGE distribution, *ANIMALS, *ENERGY metabolism, *HYDROGEN peroxide, *MITOCHONDRIA, *RATS, *SEX distribution, *TRANSCRIPTION factors, *DNA-binding proteins, *OXYGEN consumption
Abstract

The incidence of cardiac disease is age and sex dependent, but the mechanisms governing these associations remain poorly understood. Mitochondria are the organelles in charge of producing energy for the cells, and their malfunction has been linked to cardiovascular disease and heart failure. Interestingly, heart mitochondrial content and functionality are also age and sex dependent. Here we investigated the combinatory effects of age and sex in mitochondrial bioenergetics that could help to understand their role on cardiac disease. Cardiac mitochondria from 6- and 24-month-old male and female Wistar rats were isolated, and the enzymatic activities of the oxidative-phosphorylative complexes I, III, and IV and ATPase, as well as the protein levels of complex IV, β-ATPase, and mitochondrial transcription factor A (TFAM), were measured. Furthermore, heart DNA content, citrate synthase activity, mitochondrial protein content, oxygen consumption, and H2O2 generation were also determined. Results showed a reduction in heart mitochondrial mass and functionality with age that correlated with increased H2O2 generation. Moreover, sex-dependent differences were found in several of these parameters. In particular, old females exhibited a significant loss of mitochondrial function and increased relative H2O2 production compared with their male counterparts. The results demonstrate a sex dimorphism in the age-associated defects on cardiac mitochondrial function. [ABSTRACT FROM AUTHOR]

Published
2015
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