Epithelial-mesenchymal plasticity (EMP) and tumor cell migration play an important role in cancer progression, and an improved understanding of the mechanisms underlying these concepts is essential... Show moreEpithelial-mesenchymal plasticity (EMP) and tumor cell migration play an important role in cancer progression, and an improved understanding of the mechanisms underlying these concepts is essential for developing new targeted approaches. In this thesis, we studied these mechanisms using mathematical and computational approaches.First, we summarized and reviewed previous computational approaches that have been used to decipher EMP regulation. We then created mathematical models to explore (1) how different regulatory networks can explain epithelial-mesenchymal transition (EMT) in different cell contexts, and (2) how EMP and immune regulation can interact to cause tumor immunoevasion.Next, we studied the role of cell density in migration characteristics of triple-negative breast cancer cell lines by using a combined experimental and computational approach. We show how clustering and pseudopodial dynamics, potentially influenced by EMT-related factors, can alter the migratory behavior of these cell lines.Jointly, our work has shown that computational modeling can be used to test hypotheses based on experimental data, and generate testable hypotheses, making it a valuable addition to wet-lab experiments. Importantly, we identified mechanisms related to potential therapeutic targets, hopefully leading to improved targeted therapies and reduced cancer mortality. Show less
The overarching goal of this thesis was to examine the behavioral, computational, and neural mechanisms underlying social learning in adolescence. The first aim was to examine developmental... Show moreThe overarching goal of this thesis was to examine the behavioral, computational, and neural mechanisms underlying social learning in adolescence. The first aim was to examine developmental patterns across adolescence of two forms of social learning: (1) learning about other people, specifically, whether they are (un)cooperative and (un)trustworthy, and (2) learning for other people (prosocial learning) to know what actions may benefit or help others. I made use of multiple experimental paradigms based on well-known economic games and/or probabilistic reinforcement learning paradigms to assess these forms of social learning. Secondly, I aimed to examine underlying mechanisms and factors that account for age-related and individual differences in social learning. Applying computational modeling and functional neuroimaging as additional tools contributed to a better understanding of the underlying mechanisms and how these develop across adolescence. The findings in this thesis converge to early-to-mid adolescence as a key developmental period for developing well-adjusted social behaviors, and especially in the cooperative domain there are pronounced improvements. These studies make an important contribution to the literature on social development and learning, and may eventually contribute to interventions targeted at promoting well-adjusted behavior in typically developing adolescents, as well as youth with maladaptive social tendencies. Show less
