Mathematical Modeling of Cellular Signaling

Modeling TNFα-induced NFκB signaling in primary murine hepatocytes using quantitative experimental data and parameter estimation to understand dynamic signal transduction.

Overview

My early career training was rooted in systems biology, particularly mathematical modeling of biological processes. Under the supervision of Prof. Dr. Ursula Kummer at the Bioquant Research Institute, University of Heidelberg, I modeled the tumor necrosis factor alpha (TNFα)-induced activation of NFκB signaling.

Using quantitative data from primary murine hepatocytes, I built and validated an ordinary differential equation (ODE) model of the signaling pathway, estimating kinetic parameters and analyzing sensitivity to perturbations.

Methods

• ODE-based mathematical modeling of signaling cascades
• Parameter estimation from quantitative time-course data
• Parameter sensitivity analysis
• Experimental data from primary murine hepatocytes

Key Findings

The model successfully recapitulated dynamic NFκB activation patterns observed experimentally and identified key parameters controlling signal amplitude and oscillation frequency — providing mechanistic insight into how hepatocytes process inflammatory signals.

Relevant Publications

• Pinna F, Sahle S, Beuke K, Bissinger M, Tuncay S (maiden name), D’Alessandro LA, Gauges R, Raue A, Timmer J, Klingmüller U, Schirmacher P, Kummer U, Breuhahn K. A Systems Biology Study on NFκB Signaling in Primary Mouse Hepatocytes. Front Physiol. 2012;3:466. PubMed PMID: 23293603; DOI: 10.3389/fphys.2012.00466; PubMed Central PMCID: PMC3533138.