Mathematical modeling

My early career was focused on training in and applying systems biology approaches, particularly mathematical modeling, to biological processes. Under the supervision of Dr. Ursula Kummer, I modeled the tumor necrosis factor alpha (TNFα) induced activation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling using quantitative data from primary hepatocytes. TNFα is a proinflammatory cytokine that activates the NF-κB signaling pathway and is involved in priming of quiescent liver cells. Previous studies have used data from tumor cells thereby modeling this process in the context of cancer. For my master’s thesis, we modified these models and combined them with time resolved gene expression and phosphorylation measurements of pathway components. This revealed the need to include an additional phosphorylation state of the NFκB isoform p65 in the mathematical model to be able to capture the dynamics of pathway activation in primary hepatocytes. Furthermore, the model could predict the dynamics of complex formation between p65 and inhibitor of NFκB (IκB) which was experimentally validated. I was responsible for the initial model generation, quantitative data integration and parameter estimation. The model I developed was further advanced and published as a hepatocyte-specific model for TNFα-induced NF-κB signaling.

• 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.