Marielle Boonen

Prof. Marielle Boonen is leading a research group focusing on intracellular trafficking biology. She focuses in particular on lysosomes, acidified intracellular organelles containing close to 60 different acid hydrolases. This large arsenal of proteins assume the break-down of macromolecules delivered to the lysosomes by endocytosis or autophagy into primary components that can be recycled to the cytosol to re-enter biosynthetic reactions. This recycling function depends on the many transporters that are embedded in the limiting membrane of the lysosomes. When unable to degrade the macromolecules, or to translocate their degradation products to the cytosol, the abnormal accumulation of material in the lysosomes causes lysosomal and cellular dysfunctions. To date, approximately fifty lysosomal storage diseases have been reported, many of them characterized by neurodegeneration, severe organ failure, and premature death. Lysosomal alterations have also been associated with the negative evolution of other pathologies, including cancer, atherosclerosis, and Alzheimer’s and Huntington’s disease. Interestingly, increasing evidence point out that the lysosomes not only degrade macromolecules, but also control cell growth and survival by serving as signaling platforms.

The study of the underlying causes of lysosomal dysfunctions has pointed out that to maintain a well-oiled lysosomal machine and hence prevent deleterious cellular/tissue alterations, the cells must express all required lysosomal proteins and lysosomal-associated proteins but, most importantly, they also need to efficiently and specifically target them to the lysosomal compartment. To meet this second requirement, the cells rely on several intracellular trafficking machineries that transport newly synthesized lysosomal membrane or soluble proteins to their residence site within the cells.

In the lab, we are particularly interested in these transport mechanisms, as well as in the lysosomal functions in general. We notably use different models to study the underlying causes and consequences of lysosomal storage disorders and other lysosome-associated diseases, with a special focus on subcellular trafficking-related questions.