Research

Our laboratory is focused on understanding the molecular biology of membrane transport in a disease-related context covering Alzheimer’s disease and congenital disorders of glycosylation type II

We are driven to elucidate molecular mechanisms that are at the roots of Alzheimer’s disease. We focus on endolysosomal abnormalities and intraneuronal accumulations of toxic Aβ peptides, as both phenomena are congruent preclinical signs of Alzheimer's disease pathogenesis.

We hypothesize that in familial Alzheimer's, where mutations in the PSEN and APP genes favor the production of longer Aβ species, excess of endosomal (oligomeric) longer Aβ may hamper sorting mechanisms, intracellular cholesterol trafficking and even compromise the physical integrity of endo-lysosomal compartments. In turn, in late onset Alzheimer's disease, a similar sequence of events may be preceded by a dysfunction in endosomal sorting/recycling and/or lysosomal flux alterations, all known to affect amyloidogenesis and Aβ turnover. While underlying causes can be multifactorial, many risk factors for late onset Alzheimer's relate to cholesterol homeostasis and endolysosomal transport regulation (eg BIN1, PICALM, CD2AP, PLD3). Knowing how these risk factors contribute to neuronal endolysosomal flux and handling of Aβ turnover/production is important to understand earlier stages in the disease process.