11 January 2016

Prof. Bart Staels about RESOLVE

Bart STAELS, IPL, Lille – RESOLVE Partner 4

Leader of WP5 “Humanization of the computational model through the direct use of clinical data”


What is the expertise / knowledge that you bring into the RESOLVE project?

IPL brings expertise in transcriptional regulation of lipid and glucose metabolism, as well as in the cross-talk pathways between lipid and glucose metabolism, which is the primary topic of research in the RESOLVE project. IPL has developed expertise in the field of non-alcoholic fatty liver disease and its link with cardiovascular disease, amongst others via effects on atherogenic dyslipidemia. Moreover, IPL has expertise in the pharmacological modulation of these metabolic pathways by nuclear receptors.

The IPL laboratory, thanks to multiple facilities, has extensive expertise in transgenic mouse models, animal physiology, functional genomics and transcriptomics, cell culture and has active collaboration with clinical researchers.

What is your role in the RESOLVE project and why is your data relevant for the consortium?

The role of IPL is situated at two levels.

First, IPL is involved in ‘Longterm mouse experiments’ (WP4) by studying the role of activation of the hepatic nuclear receptor PPARalpha on lipid and glucose metabolism perturbations induced by atherogenic-dyslipidemic high fat/high sucrose/high cholesterol diets in apoE3Leiden CETP transgenic mice and wild type and PPARalpha-deficient mice. The data obtained will be useful in the verification of the model predictions.

Second, IPL is involved in the humanization and extension of the computational model by generating clinical data on overweight patients before (WP5; B Staels is the leader of WP5) and after interventions (diet, surgery, drug) (WP6). Bart Staels has an active collaboration with the clinician Luc van Gaal (Antwerpen, Belgium; UZA, RESOLVE Partner 9) since several years and established during the FP6 EU contract HEPADIP (2005-2010). IPL, together with UZA, have identified differentially expressed genes/pathways according to metabolic and liver status by transcriptomic analysis of liver biopsies (collected by UZA) from overweight and obese patients before (WP5) and after interventions (WP6). The transcriptomic analyses generate data that will be used in the genomescale metabolic model (GSMM), which is one of the modelling systems used in RESOLVE to connect lipid and glucose metabolism.

What are the challenges, in your opinion, in the project?

The challenges are to obtain a functional human relevant model, to better understand the connections between development of dyslipidemia/hyperglycemia/low HDL level and associated diseases (liver status) in the metabolic syndrome, but also to be useful for further fundamental research to identify new avenues to explore and/or to better understand these pathologies.

How can RESOLVE help your research?

RESOLVE is a scientific consortium that opens new opportunities of collaborations in the domain of lipid/glucose metabolism. Moreover, RESOLVE generates the possibility to correlate transcriptomic and metabolic data of the UZA human cohort, thus generating data for RESOLVE as well as new hypothesis which then need to be tested at the bench. The integration of biology expertises with mathematical modelling generated through RESOLVE is a major asset to advance our understanding of complex pathophysiological conditions. In this way, RESOLVE is truly unique.

How do you think, can system approaches help your research?

System approaches is an original approach, not readily exploited in biology laboratories such as IPL and thanks to RESOLVE this is now feasible. This recent and interesting strategy should allow the identification of new and unexplored ways in scientific projects in progress in the IPL laboratory.

How close is your science to the community and patients with the metabolic syndrome?

The research performed in the IPL laboratory combines basic research on preclinical models and cell culture models with translational approaches via collaborations with clinicians. Such collaborations with several clinicians who are specialists in the care of overweight and obese patients allows IPL to expand its translational approaches via access to patient tissues (liver, adipose tissue, intestine), allowing translation of results obtained from fundamental research to the patient level.

What are, in your opinion, directions of decisions that are vital to the progress of systems medicine?

One direction of research will be to study the impact of the environment, especially nutrition (ex: fatty acids), on the development/progression/regression of metabolic diseases for a better care of overweight/obese patients, in parallel to drug strategies.