MAURO CESAR CAFUNDO DE MORAIS
Projetos de Pesquisa
Unidades Organizacionais
LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina
5 resultados
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- Lessons and perspectives for applications of stochastic models in biological and cancer research(2018) SABINO, Alan U.; VASCONCELOS, Miguel Fs; SITTONI, Misaki Yamada; LAUTENSCHLAGER, Willian W.; QUEIROGA, Alexandre S.; MORAIS, Mauro Cc; RAMOS, Alexandre F.The effects of randomness, an unavoidable feature of intracellular environments, are observed at higher hierarchical levels of living matter organization, such as cells, tissues, and organisms. Additionally, the many compounds interacting as a well-orchestrated network of reactions increase the difficulties of assessing these systems using only experiments. This limitation indicates that elucidation of the dynamics of biological systems is a complex task that will benefit from the establishment of principles to help describe, categorize, and predict the behavior of these systems. The theoretical machinery already available, or ones to be discovered to help solve biological problems, might play an important role in these processes. Here, we demonstrate the application of theoretical tools by discussing some biological problems that we have approached mathematically: fluctuations in gene expression and cell proliferation in the context of loss of contact inhibition. We discuss the methods that have been employed to provide the reader with a biologically motivated phenomenological perspective of the use of theoretical methods. Finally, we end this review with a discussion of new research perspectives motivated by our results.
conferenceObject Stochastic model of contact inhibition and the proliferation of melanoma in situ.(2018) MORAIS, Mauro Cesar C.; STUHL, Izabella; SABINO, Alan U.; LAUTENSCHLAGER, Willian W.; QUEIROGA, Alexandre S.; TORTELLI JR., Tharcisio C.; CHAMMAS, Roger; SUHOV, Yuri; RAMOS, Alexandre F.bookPart Evolução do tratamento do câncer(2015) MORAIS, Mauro C. Cafundó de; JúNIOR, Gilberto de Castro- Stochastic modeling for investigation of the regulation of transcription of the RKIP gene(2020) RAMOS, A. F.; GAMA, L. dos Reis; MORAIS, M. C. C. de; MARTINS, P. C. de MeloThe plethora of intracellular compounds interacting in well-orchestrated networks of chemical reactions, and the unavoidable randomness caused by low copy numbers of reactants, are main characteristics of the intracellular environment. That results on a huge amount of possible interactions and points out a major difficulty of employing the currently available experimental techniques to understand cellular behavior. In general, well controlled experiments deal with few elements selected accordingly with a set of biological principles to describe, categorize, and predict the dynamics of a biological system. However, those mostly qualitative principles may be insufficient for understanding some cellular phenomena and the application of theoretical tools usually developed within the scope of physics, mathematics, statistics, and computer sciences that might provide additional insights for cancer biologists. In this chapter, we present a stochastic approach to the regulation of gene transcription using a constitutive and binary stochastic model. We present the exact solutions for those models and introduce a framework for using those models in a treatment context targeting the regulation of gene expression. A discussion on the limitations of our approach and on the possible biological scenarios to which it applies is presented aiming at the design of therapeutic strategies changing Raf kinase inhibitory protein (RKIP) expression levels. © 2020 Elsevier Inc. All rights reserved.
- Peri/epicellular protein disulfide isomerase-A1 acts as an upstream organizer of cytoskeletal mechanoadaptation in vascular smooth muscle cells(2019) TANAKA, Leonardo Y.; ARAUJO, Thais L. S.; I, Andres Rodriguez; FERRAZ, Mariana S.; PELEGATI, Vitor B.; MORAIS, Mauro C. C.; SANTOS, Aline M. dos; CESAR, Carlos L.; RAMOS, Alexandre F.; ALENCAR, Adriano M.; LAURINDO, Francisco R. M.Although redox processes closely interplay with mechanoresponses to control vascular remodeling, redox pathways coupling mechanostimulation to cellular cytoskeletal organization remain unclear. The peri/epicellular pool of protein disulfide isomerase-A1 (pecPDIA1) supports postinjury vessel remodeling. Using distinct models, we investigated whether pecPDIA1 could work as a redox-dependent organizer of cytoskeletal mechanoresponses. In vascular smooth muscle cells (VSMCs), pecPDIA1 immunoneutralization impaired stress fiber assembly in response to equibiaxial stretch and, under uniaxial stretch, significantly perturbed cell repositioning perpendicularly to stretch orientation. During cyclic stretch, pecPDIA1 supported thiol oxidation of the known mechanosensor beta(1)-integrin and promoted polarized compartmentalization of suifenylated proteins. Using traction force microscopy, we showed that pecPDIA1 organizes intracellular force distribution. The net contractile moment ratio of platelet-derived growth factor-exposed to basal VSMCs decreased from 0.90 +/- 0.09 (IgG-exposed controls) to 0.70 +/- 0.08 after pecPDIA1 neutralization (P < 0.05), together with an enhanced coefficient of variation for distribution of force modules, suggesting increased noise. Moreover, in a single cell model, pecPDIA1 neutralization impaired migration persistence without affecting total distance or velocity, whereas siRNA-mediated total PDIA1 silencing disabled all such variables of VSMC migration. Neither expression nor total activity of the master mechanotransmitter/regulator RhoA was affected by pecPDIA1 neutralization. However, cyclic stretch-induced focal distribution of membrane-bound RhoA was disrupted by pecPDI inhibition, which promoted a nonpolarized pattern of RhoA/caveolin-3 cluster colocalization. Accordingly, FRET biosensors showed that pecPDIA1 supports localized RhoA activity at cell protrusions versus perinuclear regions. Thus. pecPDI acts as a thiol redox-dependent organizer and noise reducer mechanism of cytoskeletal repositioning, oxidant generation, and localized RhoA activation during a variety of VSMC mechanoresponses. NEW & NOTEWORTHY Effects of a peri/epicellular pool of protein disulfide isomerase-A1 (pecPDIA1) during mechanoregulation in vascular smooth muscle cells (VSMCs) were highlighted using approaches such as equibiaxial and uniaxial stretch, random single cell migration, and traction force microscopy. pecPDIA1 regulates organization of the cytoskeleton and minimizes the noise of cell alignment, migration directionality, and persistence. pecPDIA1 mechanisms involve redox control of beta(1)-integrin and localized RhoA activation. pecPDIA1 acts as a novel organizer of mechanoadaptation responses in VSMCs.