Cellular and Molecular Pharmacology

Bruxelles Woluwe

Overview of 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.

A first part on the lab (Joseph H. Lorent) investigates on a molecular level how certain aspects of cell membranes, such as the formation of lateral membrane domains, membrane asymmetry, membrane biophysical and membrane mechanical properties guide susceptibility or therapeutic resistance of bacteria and cancer cells. Once we discover the underlying mechanisms, we aim to develop drugs that target these mechanisms and specifically kill or reduce chemotherapeutic resistance in bacteria or cancer cells.

A second part of the lab (Françoise Van Bambeke) focuses specifically on the treatment of bacterial infections, resistance, and persistence mechanisms. On a molecular level, we investigate 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, bioinformatics, cancer biology, cellular and molecular biology, molecular and clinical pharmacology and more (see in details).