Cellular and Molecular Pharmacology

Bruxelles Woluwe

Different studies led in the Cellular and Molecular Pharmacology lab (FACM).

We are a multidisciplinary team with the long-term goal to discover and optimize treatments mainly related to anti-infective agents. New treatment approaches in this field are utterly necessary since the World Health Organization predicts that the main cause of death in 2050 will be from infections that will have become untreatable due to antimicrobial resistance.

For the discovery of new targets, resistance and persistence mechanisms, a part of our laboratory focuses on the bacterial cell envelope and especially membranes. Bacterial membranes possess peculiar biophysical properties, different from human cells, that are regulated by numerous proteins. Membranes also regulate access of antibiotics to intracellular targets by regulating membrane diffusion or efflux pumps and hereby inducing antibiotic resistance. Membranes constitute therefore excellent pharmacological targets for antibacterial agents. A second focus lies on the discovery and characterization of persistence mechanisms in bacteria such as biofilm formation, molecular switches of persister cells and survival mechanisms of intracellular bacteria.

To optimize common treatments, we aim at increasing the efficacy of common antibiotics by counteracting bacterial defense mechanisms or improving intracellular pharmacokinetics. In this perspective, we investigate how resistance and persistence mechanisms decrease antibiotic efficacy by modulating bacterial homeostasis. One approach aims at improving intra-bacterial availability of common antibiotics by increasing outer membrane diffusion or inhibiting efflux pumps. The study of bacterial infections inside human host cells helps us to improve cellular pharmacokinetics (accessibility to the antibiotic inside the host cell) and cellular pharmacodynamics (efficacy) of antimicrobial drugs during more life-like situations. These intracellular infection studies are complementarily conducted to toxicity studies in human cells to anticipate deleterious side effects in vivo.

In a broader context, our translational research activities include in vivo studies on mice and clinical trials aimed at optimizing antibiotic use (adaptation of their mode of administration or daily dosage) with the aim to increase their efficacy and/or reduce their toxicity (run in collaboration with different hospitals in Belgium), and collection of clinical isolates for which we study antibiotic resistance and try to establish a potential link with the treatment received by the patient.

Disciplines and applied methodologies involve microbiology, membrane biophysics, biochemistry, analytical chemistry, cellular and molecular biology, molecular and clinical pharmacology.