Mathematical modeling of inflammation in endotoxemia, hemorrhage, and trauma

Description of projects available to graduate students:
Severe infection and trauma elicit an acute inflammatory response that can lead to shock. This process involves migration and activation of leukocytes, secretion of cytokines, and the production of free radicals, which may result in organ dysfunction and death. Numerous attempts to modulate specific components of this inflammatory cascade have failed as therapies, possibly because the ultimate outcome of inflammation depends crucially on a complex interplay of interacting elements. A mathematical model that can capture the interacting global dynamics of all the elements of the inflammatory cascade may be useful to grasp this complexity. Drs. Clermont (Critical Care Medicine), Chow (Mathematics) and I have created a mathematical model describing the mediators of acute inflammation that is designed to capture the response of mice subjected to endotoxemia, surgical trauma, and hemorrhagic shock. The animal data and model output suggests that there is a common inflammatory response underlying diverse shock states. We have also modeled and obtained validating data in combination injury scenarios, as well as in humans subjected to experimental endotoxemia. This work may lead to novel diagnostics for the treatment of post-traumatic or -septic inflammation, as well as to the design of new therapeutics for these indications. We are currently pursuing numerous projects related to this mathematical model, including animal experiments in models of bacterial infection, trauma, hemorrhage, and endotoxemia; augmentation of the model with data related to adaptive immune elements (e.g. T cells and dendritic cells); and extension of this model to additional inflammatory scenarios.

Techniques graduate student will learn:
mouse and rat sugery; ELISA; flow cytometry; mathematical modeling