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Students

Christoph Hethey
Pharmacist / Universität Potsdam

Begin: March 2013 - End: September 2017
Supervisor: Prof. Wilhelm Huisinga
Co-Supervisor: Prof. Charlotte Kloft
Mentor: Boehringer Ingelheim

PhD Project

Cell physiology based pharmacodynamic modeling of antimicrobial drug combinations (PhD thesis)

Scientific interests

In a broader sense, I am interested in translating real-life problems into mathematical ones, which are then solved computationally. My research focus is on life-sciences, in particular PKPD modelling.

Antibiotic combinations are indispensable tools to face the antimicrobial resistance crisis. The observation that the mechanism of drug action is highly relevant for the prediction of antibiotic interactions motivated the development of a new mechanism based model of bacterial growth. During my PhD project, I successfully exploited the link between the cell-state of a reference cell and the exponential growth rate constant to implement clinically relevant antibiotics according to their corresponding mechanisms of action on the cellular level. Employing Markov chain Monte Carlo techniques for Bayesian parameter inference, I analysed cell-level data for E. coli and S. aureus combined with extensive time-kill curve data including dual combinations of linezolid, meropenem, vancomycin, chloramphenicol and tetracycline. The model correctly predicts even complex growth dynamics like antibiotic auto-inhibition, persistence and regrowth. For the first time, a unified approach disentangles the effects of the experimental protocol (represented in the definition of the reference cells) on the classification of antibiotic interactions in terms of additivity, antagonism and synergy. As the optimization of experimental protocols to discover valuable drug combinations is topic of current research, such insight is critical.

Beside the PhD project, I worked on modeling hepatic drug metabolism (part of a joint project with the Bayer AG), aluminum toxicokinetics (part of a joint project with the Paul-Ehrlich-Institute) and contribute regularly to courses in the PharMetrX module curriculum (on PBPK modeling and systems biology).

Presentations

Education

  • since 10/2017: Head of Junior Research Group at the Federal Institute of Risked Assessment (BfR/Berlin)
  • 03/2013-: Graduate Research Training Program 'Pharmacometrics & Computational Disease Modelling' at the Universität Potsdam
  • 2012 - 2013: Preregistration student at Vita Apotheke in Berlin (including approbation as registered pharmacist)
  • 2011 - 2012: Preregistration student at Bayer Quality Control in Berlin
  • 2007 - 2011: Undergraduate studies of pharmacy at WWU in Münster & student trainee at Eimermacher GmbH