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6 p, 3.0 MB |
Minimum action path theory reveals the details of stochastic transitions out of oscillatory states
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Cruz Moreno, Roberto de la (Universitat Autònoma de Barcelona. Departament de Matemàtiques) ;
Perez-Carrasco, Ruben (University College London. Department of Mathematics (UK)) ;
Guerrero, Pilar (University College London. Department of Mathematics (UK)) ;
Alarcón Cor, Tomás (Universitat Autònoma de Barcelona. Departament de Matemàtiques) ;
Page, Karen M. (University College London. Department of Mathematics (UK)) ;
Universitat Autònoma de Barcelona.
Centre de Recerca Matemàtica
Cell state determination is the outcome of intrinsically stochastic biochemical reactions. Transitions between such states are studied as noise-driven escape problems in the chemical species space. Escape can occur via multiple possible multidimensional paths, with probabilities depending nonlocally on the noise. [...]
2018 -  10.1103/PhysRevLett.120.128102
Physical review letters, Vol. 120, Issue 12 (March 2018) , art. 128102
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27 p, 3.0 MB |
A multiscale model of epigenetic heterogeneity-driven cell fate decision-making
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Folguera Blasco, Núria (Universitat Autònoma de Barcelona. Departament de Matemàtiques) ;
Pérez Carrasco, Rubén (University College London. Department of Mathematics) ;
Cuyàs, Elisabet (Institut d'Investigació Biomèdica de Girona) ;
Menendez, Javier A. (Institut d'Investigació Biomèdica de Girona) ;
Alarcón Cor, Tomás (Universitat Autònoma de Barcelona. Departament de Matemàtiques) ;
Universitat Autònoma de Barcelona.
Centre de Recerca Matemàtica
The inherent capacity of somatic cells to switch their phenotypic status in response to damage stimuli in vivo might have a pivotal role in ageing and cancer. However, how the entryexit mechanisms of phenotype reprogramming are established remains poorly understood. [...]
2019 - 10.1371/journal.pcbi.1006592
PLoS computational biology, Vol. 15, Issue 4 (April 2019) , art. e1006592
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19 p, 13.4 MB |
Germline BRCA1 mutation reprograms breast epithelial cell metabolism towards mitochondrial-dependent biosynthesis : evidence for metformin-based "starvation" strategies in BRCA1 carriers
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Cuyàs, Elisabet (Molecular Oncology Group, Girona Biomedical Research Institute (IDIBGI), Girona, Catalonia, Spain) ;
Fernández-Arroyo, Salvador (Hospital Universitari Sant Joan de Reus) ;
Alarcón, Tomás (Universitat Autònoma de Barcelona. Departament de Matemàtiques) ;
Joven, Jorge (Hospital Universitari Sant Joan de Reus) ;
Menendez, Javier A. (Molecular Oncology Group, Girona Biomedical Research Institute (IDIBGI), Girona, Catalonia, Spain)
We hypothesized that women inheriting one germline mutation of the BRCA1 gene ("one-hit") undergo cell-type-specific metabolic reprogramming that supports the high biosynthetic requirements of breast epithelial cells to progress to a fully malignant phenotype. [...]
2016 - 10.18632/oncotarget.9732
Oncotarget, Vol. 7 (may 2016) , p. 52974-52992
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18 p, 8.3 MB |
Suppression of endogenous lipogenesis induces reversion of the malignant phenotype and normalized differentiation in breast cancer
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Gonzalez-Guerrico, Anatilde M. (Department of Laboratory Medicine and Pathology, Division of Experimental Pathology, Mayo Clinic, Rochester, MN, USA) ;
Espinoza, Ingrid (Department of Biochemistry, University of Mississippi Medical Center, Jackson, MS, USA) ;
Schroeder, Barbara (Department of Laboratory Medicine and Pathology, Division of Experimental Pathology, Mayo Clinic, Rochester, MN, USA) ;
Park, Cheol Hong (Department of Laboratory Medicine and Pathology, Division of Experimental Pathology, Mayo Clinic, Rochester, MN, USA) ;
Chandra Mohan, KVP (Department of Laboratory Medicine and Pathology, Division of Experimental Pathology, Mayo Clinic, Rochester, MN, USA) ;
Khurana, Ashwani (Department of Laboratory Medicine and Pathology, Division of Experimental Pathology, Mayo Clinic, Rochester, MN, USA) ;
Corominas-Faja, Bruna (Molecular Oncology Group, Girona Biomedical Research Institute (IDIBGI), Girona, Spain) ;
Cuyàs, Elisabet (Molecular Oncology Group, Girona Biomedical Research Institute (IDIBGI), Girona, Spain) ;
Alarcón, Tomás (Universitat Autònoma de Barcelona. Departament de Matemàtiques) ;
Kleer, Celina (Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA) ;
Menendez, Javier A. (Molecular Oncology Group, Girona Biomedical Research Institute (IDIBGI), Girona, Spain) ;
Lupu, Ruth (Mayo Clinic Cancer Center, Rochester, MN, USA)
The correction of specific signaling defects can reverse the oncogenic phenotype of tumor cells by acting in a dominant manner over the cancer genome. Unfortunately, there have been very few successful attempts at identifying the primary cues that could redirect malignant tissues to a normal phenotype. [...]
2016 - 10.18632/oncotarget.9463
Oncotarget, Vol. 7 (may 2016) , p. 71151-71168
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13 p, 3.9 MB |
Accelerated geroncogenesis in hereditary breast-ovarian cancer syndrome
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Menendez, Javier A. (Institut d'Investigació Biomèdica de Girona) ;
Folguera-Blasco, Núria (Centre de Recerca Matemàtica) ;
Cuyàs Navarro, Elisabet (Institut d'Investigació Biomèdica de Girona) ;
Fernández-Arroyo, Salvador (Hospital Universitari de Sant Joan) ;
Joven, Jorge (Hospital Universitari de Sant Joan) ;
Alarcón Cor, Tomás (Universitat Autònoma de Barcelona. Departament de Matemàtiques)
The geroncogenesis hypothesis postulates that the decline in metabolic cellular health that occurs naturally with aging drives a "field effect" predisposing normal tissues for cancer development. We propose that mutations in the cancer susceptibility genes BRCA1/2 might trigger "accelerated geroncogenesis" in breast and ovarian epithelia. [...]
2016 - 10.18632/oncotarget.7867
Oncotarget, Vol. 7, issue 11 (March 2016) , p. 11959-11971
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11 p, 2.4 MB |
Oncometabolic nuclear reprogramming of cancer stemness
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Menendez, Javier A. (Institut Català d'Oncologia) ;
Corominas-Faja, Bruna (Institut d'Investigació Biomèdica de Girona) ;
Cuyàs, Elisabet (Institut d'Investigació Biomèdica de Girona) ;
García, María G. (Instituto Universitario de Oncología del Principado de Asturias) ;
Fernández-Arroyo, Salvador (Hospital Universitari de Sant Joan) ;
Fernández, Agustín F. (Instituto Universitario de Oncología del Principado de Asturias) ;
Joven, Jorge (Hospital Universitari de Sant Joan) ;
Fraga, Mario F. (Instituto Universitario de Oncología del Principado de Asturias) ;
Alarcón Cor, Tomás (Centre de Recerca Matemàtica)
By impairing histone demethylation and locking cells into a reprogramming-prone state, oncometabolites can partially mimic the process of induced pluripotent stem cell generation. Using a systems biology approach, combining mathematical modeling, computation, and proof-of-concept studies with live cells, we found that an oncometabolite-driven pathological version of nuclear reprogramming increases the speed and efficiency of dedifferentiating committed epithelial cells into stem-like states with only a minimal core of stemness transcription factors. [...]
2016 - 10.1016/j.stemcr.2015.12.012
Stem cell reports, Vol. 6, issue 3 (March 2016) , p. 273-283
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17 p, 1.1 MB |
Hybrid approaches for multiple-species stochastic reaction-diffusion models
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Spill, Fabian (Boston University. Department of Mechanical Engineering) ;
Guerrero, Pilar (University College London. Department of Mathematics) ;
Alarcón Cor, Tomás (Centre de Recerca Matemàtica) ;
Maini, Philip K. (Wolfson Centre for Mathematical Biology) ;
Byrne, Helen (Wolfson Centre for Mathematical Biology)
Reaction-diffusion models are used to describe systems in fields as diverse as physics, chemistry, ecology and biology. The fundamental quantities in such models are individual entities such as atoms and molecules, bacteria, cells or animals, which move and/or react in a stochastic manner. [...]
2015 - 10.1016/j.jcp.2015.07.002
Journal of computational physics, Vol. 299 (Oct. 2015) , p. 429-445
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