Speaker: Amandeep Kaur, Applied Mathematics Graduate Student
Title: Mathematical Modeling and Optimization Uncovers the Regulation of Factor Xa by TFPI
Abstract: Blood coagulation is a complex network of biochemical reactions involving positive and negative feedback. Positive feedback initiates the formation of blood clot and negative feedback stops its growth. Because both over-clotting and under-clotting result in serious, and sometimes deadly consequences, it is important to understand the regulation of coagulation by inhibitors. In this study, we investigate a specific coagulation inhibitor, tissue factor pathway inhibitor (TFPI), for which the mechanism of action is not fully understood. Previous mathematical models of TFPI have fit kinetic parameters to a single experimental time course but these models fail when applied to data from multiple experimental time courses simultaneously. We use mathematical modeling, optimization, and forward uncertainty propagation method to uncover the precise mechanism of action and to determine kinetic rates by considering multiple experimental data sets simultaneously. We found that there exist multiple parameter sets that may describe the data. Assuming uncertainty in the initial condition may help in giving a better fit. Our scheme is consistent with the previous experimental data and describe the biological phenomena better than the schemes presented in the past.