(4cq) Spatiotemporal Signaling During Cell Adhesion and Migration: Computational Models and Experimental Analysis

In order to further our understanding of how complex and dynamic interactions within a cell determine cell fate and function, we need a coordinated approach that combines experimental measurements and theoretical insights. In general, my research interests focus on the use of systems analysis, computational modeling, and quantitative experimentation to understand and manipulate complex biological systems by way of their cellular signaling systems. One specific aspect of cell signaling that interests me greatly is determining how cells coordinate and regulate the many signals required for cell migration. This process involves the precise regulation of creation, activation, degradation, and spatial localization of a multitude of proteins, small molecules, and lipids.

To date, my efforts have been divided between quantitative experimentation and computational modeling related to cell adhesion and migration. As a graduate student, I focused on the function of integrin proteins, which control cell adhesion and migration by binding extra-cellular matrix (ECM) proteins and transferring signals bi-directionally through the cell membrane. I studied the cellular response to the availability of ECM binding sites by confocal microscopy, and used probabilistic modeling to show how integrin cluster properties change as a function of ECM density. I also used computational modeling to evaluate the potential for a diffusing cascade of biochemical reactions to regulate integrin activation in space to create integrin clusters, and to postulate how integrin clustering may affect cell migration.

Recently I have been investigating the mechanisms that give rise to stochastic yet persistent behavior in migrating cells. Using stochastic computational modeling, I investigated how different feedback structures between adhesion dynamics and activation of the small GTPase Rac1 may be capable of tuning the frequencies of stochastic protrusion and adhesion events under various intracellular and extracellular conditions. Additionally, I used total internal reflection fluorescence (TIRF) microscopy to visualize proteins that shape cell adhesion and migration signals in migrating cells, and spatiotemporal analysis to understand how these signaling events may be related to cell morphology and migration behavior. This analysis approach provides specific insight into how cell signaling is influenced by cell morphology, and conversely how cell signaling may affect morphology and migration persistence by localizing cellular protrusion.

I am also especially interested in working with collaborators in the areas of cell biology, high-resolution microscopy, and biomaterials to develop cutting edge experimental and analytical approaches for understanding cell signaling and related physiological processes. Additionally, applications of engineering to biology and physiology provide exciting opportunities to infuse engineering education with topics that excite and engage students, and I am interested in developing ways to incorporate analysis of biological processes into classical chemical engineering coursework.