(172h) Integrated Modeling Framework for Signaling, Transcription and Cell Fate and Their Clinical Significance
AIChE Annual Meeting
2017
2017 Annual Meeting
Food, Pharmaceutical & Bioengineering Division
Quantitative Approaches to Disease Mechanisms and Therapies II
Monday, October 30, 2017 - 2:36pm to 2:54pm
Abstract: Cellular behavior is regulated by complex signaling networks which
in turn are influenced extracellular environment, membrane trafficking
processes and in combination regulate the nuclear events leading to
transcription. These processes operate at very different length and time
scales and key information about them like rates of interactions, expression
levels are often incomplete which makes mathematical modeling of these
networks difficult. Here we develop a general approaches to integrate
signaling models operating at different time scales and also a signaling and
trafficking model operating at different timescales. To validate the models
we performed extensive sensitivity analyses and studied the robustness and
evolvability of these models. These were utilized in interpreting the
experimental results, designing further experiments and making useful
clinical predictions. This framework was applied to a core signaling module
of Ras-MAPK, PI3K/AKT and JAK/STAT pathway which is a critical cellular
network often altered in various cancers of lung, liver and prostate. We
studied the interaction of this network with p53 mediated DNA damage
response pathway and Rab8/Rab11 regulated late endocytic recycling pathways.
in turn are influenced extracellular environment, membrane trafficking
processes and in combination regulate the nuclear events leading to
transcription. These processes operate at very different length and time
scales and key information about them like rates of interactions, expression
levels are often incomplete which makes mathematical modeling of these
networks difficult. Here we develop a general approaches to integrate
signaling models operating at different time scales and also a signaling and
trafficking model operating at different timescales. To validate the models
we performed extensive sensitivity analyses and studied the robustness and
evolvability of these models. These were utilized in interpreting the
experimental results, designing further experiments and making useful
clinical predictions. This framework was applied to a core signaling module
of Ras-MAPK, PI3K/AKT and JAK/STAT pathway which is a critical cellular
network often altered in various cancers of lung, liver and prostate. We
studied the interaction of this network with p53 mediated DNA damage
response pathway and Rab8/Rab11 regulated late endocytic recycling pathways.
Acknowledgements: This Work was supported by European Commission Grant FP7-ICT-2011-9-600841 and NIH 1U54CA193417