Pierre-Andre Billat

Research interests

Soon, we expect a breakthrough in our ability to study compound fate in living organisms by in vitro approaches. This experimenter philosopher’s stone should be the computational modeling. To date, these models are still requiring physiological mode of action data that could be provided by in vivo experiments only. The collected data enlighten several underlying patterns that feed our in silico models and from those patterns we infer more and more realistic models.

Development of in silico models to establish in vitro / in vivo correlations (IVIVC)

The current main drawback of the use of the in vitro approach is the difficulty to extrapolate data from cellular experiments to “real life”. Indeed, most in vitro models are immortalized cells growing in plastic plates, that are not representative of an organ or even of a tissue. In this context, we are looking for computational methods able to bridge the gap between the in vitro models and the whole biological systems.

While it is true that the whole cellular system could not be modeled, models considering the main compound ADME properties in cells and even organelles along with its behavior in the experimental system should give reliable macro information about the xenobiotic fate in the human body.

To date, most of the current in vitro-to-in vivo correlation (IVIVC) methods use pharmaceutical compounds, ie a tiny subgroup of molecules that have well-known properties. On the contrary, non-pharmaceutical compounds show a very wide range of physicochemical properties and few in vivo data are available.

In this context, my objectives are to improve existing IVIVC methods, apply these to chemical compounds, make them easily transposable from one in vitro model to another one, and rend the extrapolation to the in vivo systems more reliable.

Development of PBPK models focused on the inhaled route

From a modeler's point of view, the inhaled route is certainly one of the most complex routes of exposure. Indeed, the lungs could be torn into several parts of various compositions, with variable permeation to particles and gas, variable blood flows, and metabolism. Several models were developed for organic volatile compounds for which the kinetics are mainly depending on the air/blood partition coefficient. PBPK models for particles and lipophilic molecules are more difficult to develop however as the absorption is still poorly explored (in comparison with the oral route for instance).

The in vitro models developed in the research unit along with in vivo data should help to better understand the different absorption phases to calibrate a new inhalation model.

The purposes of this model will be, but not least, to assess the impact of a decrease in air quality in specific populations and to evaluate the exposure of workers or populations to inhaled chemicals.