Conceder a(o) professor(a) MUHAMAD SUBHI MAHMUD HASAN HUSEIN, lotado(a) no Colégio de Aplicação (CA/CED), afastamento em regime de tempo integral para cursar Doutorado no exterior

Bintz, Marcus

Heath, James R.

Liu, Victoria

Ng, Alphonsus H. C.

Ribas, Antoni

Robert, Lidia

Su, Yapeng

Wei, Wei

Yang, Yezi

PLoS Computational Biology

Direção do CED

Repositório Institucional da UFSC

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Phenotypic plasticity is associated with non-genetic drug tolerance in several cancers. Such plasticity can arise from chromatin remodeling, transcriptomic reprogramming, and/or protein signaling rewiring, and is characterized as a cell state transition in response to molecular or physical perturbations. This, in turn, can confound interpretations of drug responses and resistance development. Using BRAF-mutant melanoma cell lines as the prototype, we report on a joint theoretical and experimental investigation of the cell-state transition dynamics associated with BRAF inhibitor drug tolerance. Thermodynamically motivated surprisal analysis of transcriptome data was used to treat the cell population as an entropy maximizing system under the influence of time-dependent constraints. This permits the extraction of an epigenetic potential landscape for drug-induced phenotypic evolution. Single-cell flow cytometry data of the same system were modeled with a modified Fokker-Planck-type kinetic model. The two approaches yield a consistent picture that accounts for the phenotypic heterogeneity observed over the course of drug tolerance development. The results reveal that, in certain plastic cancers, the population heterogeneity and evolution of cell phenotypes may be understood by accounting for the competing interactions of the epigenetic potential landscape and state-dependent cell proliferation. Accounting for such competition permits accurate, experimentally verifiable predictions that can potentially guide the design of effective treatment strategies

Yapeng Su

Marcus Bintz

Yezi Yang

Lidia Robert

Alphonsus H C Ng

Victoria Liu

Antoni Ribas

James R Heath

Wei Wei

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Phenotypic heterogeneity and evolution of melanoma cells associated with targeted therapy resistance.

Caltech Authors - Main

Phenotypic heterogeneity and evolution of melanoma cells associated with targeted therapy resistance

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Repositório Institucional da UFSC

Directory of Open Access Journals

Caltech Authors - Main

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Caltech Authors - Main