Meet the Expert

Learn what Dr. Jeroen Vanoirbeek, a scientist at the forefront of the preclinical toxicology research, has to say about his research and the current state of the field.

Dr. Jeroen Vanoirbeek is a research Associate Professor at KU Leuven. His interests are occupational and environmental exposure assessment and toxicology, with a special focus on experimental lung immune toxicology.

Interview:

What is your research training background? How did you get there?

I am a biologist from training, with a major in animal physiology and molecular biology. As it was impossible to stay at the biology department, I moved to the medical department whereby coincidence I came into the lung toxicology group of prof. Ben Nemery. In this team, there was a large focus also on lung physiology and how to measure it in animal models, which triggered my fascination for this research field. This research topic perfectly aligned with my master training and was a perfect match.

Why did you stay in the pulmonary physiology field?

After my PhD, I felt that the research I set up in occupational asthma and chemical exposure leading to respiratory problems was not finished. I needed at least a postdoc period to finalize what I started and have some kind of closure there. Yet, as happens often, during my postdoc, new ideas arose even more and I began writing and obtaining grants for various projects on research which fascinated me. This led to a relatively unexpectedly in an academic position. From then on, I have been diving deeper into exposure sciences, immunology, receptor physiology, lung function measurements and this has remained the center of my research interest.

How does the general landscape of occupational toxicology look?

In addition to preclinical models of asthma and COPD, I am also focusing a little bit on exposure sciences with air quality and pollution. I am trying to combine both exposure sciences with knowledge on the lung toxicology and physiology. What I noticed a lot during my PhD and postdoc was that the interest in lung physiology and physiological measurements in animal models was rather low or even to say almost absent. Most of the focus in the asthma field then was the Th1/Th2 paradigm, followed by a trendy focus on the dendritic cells and cytokine profiles. It was surprising that there was not so much interest in lung physiology and breathing mechanisms and how these immune mediators would affect lung function in disease models. I set out to work on this gap in knowledge and I noticed in the last 5-10 years that more and more groups are also including these translatable lung function parameters which are essential to understand lung physiology. I think it is good that recently more and more pulmonology researchers, with an interest in lung physiology are along with immunologists again interested in the asthma research.

What are the real-world implications of your research?

In my research, I mostly investigate the effects of chemical exposure, such as occurs in big industries like the petrochemical industry where you have glues or resins production. Many of these chemicals are used in our daily life and fabricated first in large scale by industrial companies. It was not only the classical allergens that cause asthma, but it seems that some of these chemical compounds are also sensitizers and can cause asthma. What my research basically does is identifying these respiratory sensitizers and making sure that people who have to produce them and work with them in large amounts the whole day are better protected. It involves respiratory protection from inhalation but also skin protection. Indeed, in our studies we found that skin exposure followed by an inhalation of a very low concentration of certain occupation chemical compounds could also lead to respiratory problems, such as asthma. Therefore, this twofold protection, respiratory and dermal, is very important to people getting exposed to all these noxious chemicals.

Which preclinical pulmonary equipment has been instrumental in your research?

I started out with whole body plethysmography in the beginning of my career. With this equipment we performed both baseline ventilatory parameters along with methacholine challenges. Next, we moved on to the legacy flexiVent and we had almost 10-years of high-quality research with this version. We then upgraded to the new flexiVent FX which is of course a fantastic tool. In parallel, I also shifted to longitudinal measurements through double chamber plethysmography which is now more used due to its ability to do longitudinal measurements in conscious, restrained animals. Compared to 15-20 years ago, I was not so much aware of which parameters would be good identifiers of lung diseases in these non-invasive tools but I am now more confident about which parameters are key for investigating airway irritation like end-inspiratory and end-expiratory pause, tidal volume, peak inspiratory/expiratory flow changes and how these behave in different lung diseases.

In the last five years, we have been using the flexiVent’s Forced Expired Volume (FEV) extension which allows clinical correlation (Forced Expired Volume/Forced Vital Capacity; FEV/FVC). Still there are caveats as the negative pressure expiration is passive perturbation and is not quite mimicking the active effort of spirometry in a clinical setting. Yet, preclinical lung function parameters should lean as much as possible to clinical human diagnostics, in order to translate the findings in animal models easier to the human situation. This will result in time to better estimations on possible improvement by therapeutics in humans vs the results obtained in animal models.

Regarding the models, are you working only on mice? Which kind of strains?

The main research we have is on C57BL/6J mice, because of the availability of multiple knockout mice. In my experience every mouse strain has a different baseline lung function parameters. I noticed a lot of variability between the different knockout strains, so you always want to make sure that you have litter mates in an experiment when comparing WT vs KO mice. We are also using neonate rabbit pups, which are very useful to investigate bronchopulmonary dysplasia research. Rabbit pups have another lung development and physiology compared to mice, which is more similar to the human situation. Towards the future, we are also planning to assess lung function (non-invasive and invasive) in mouse and rat transplantation models.

What advice do you have for someone who is starting out in this research?

My advice is to inform themselves really well before they start and then take enough time to get acquainted with lab instruments to assess lung function. This involves doing a lot of testing on the anesthesia you need, in case of invasive measurements. You need to understand which measurements you are performing, what the outcome parameters are, which are the benefits and limitations, rather than just clicking buttons to follow a protocol without understanding it. There are many experts to help you at emka&SCIREQ, but also in academia with researchers like myself who are willing to help with this kind of data interpretation.

Dr. Vanoirbeek ’s recent publications:

Devos, F. C., Maaske, A., Robichaud, A., Pollaris, L., Seys, S., Lopez, C. A., … & Vanoirbeek, J. A. (2017). Forced expiration measurements in mouse models of obstructive and restrictive lung diseases. Respiratory research, 18(1), 1-14.

Vanoirbeek, J. A., Rinaldi, M., De Vooght, V., Haenen, S., Bobic, S., Gayan-Ramirez, G., … & Janssens, W. (2010). Noninvasive and invasive pulmonary function in mouse models of obstructive and restrictive respiratory diseases. American journal of respiratory cell and molecular biology, 42(1), 96-104.

Dekoster, K., Decaesteker, T., Berghen, N., Van den Broucke, S., Jonckheere, A. C., Wouters, J., … & Velde, G. V. (2020). Longitudinal micro-Computed Tomography-derived biomarkers quantify non-resolving lung fibrosis in a silicosis mouse model. Scientific reports, 10(1), 1-10.

Learn more about the flexiVent techniques and measurements here:

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