The Lapierre laboratory uses a combination of biochemical, genetic and molecular approaches to study aging in cell systems, model organisms and murine models. Our focus is to expand our understanding of the biology of aging by investigating the autophagy-lysosome pathway, a central longevity mechanism.
LYSOSOME BIOLOGY
Lysosomes serve as major intracellular degradation organelles by breaking down and recycling macromolecules into metabolites that can be utilized to synthesize new molecules and organelles. In addition, lysosomes have emerged as signaling hubs that regulate how cells respond to nutrient deprivation and environmental stresses. Our goals are to understand how lysosomes modulate metabolism and signaling, and how their dysfunction drives aging.
REGULATORY NETWORK OF AUTOPHAGY
Autophagy, the cellular process of engulfing its own macromolecules using lipid membranes, leads to the degradation of damaged macromolecules by sequestration and delivery to the lysosome. Longevity-related transcription factors mediate the activation of the transcription of numerous autophagy proteins, but their regulation is not fully understood. Our goals are to elucidate the regulatory network modulating the activity of these transcription factors as well as the epigenetic regulations associated with their targets in the context of Alzheimer’s disease and aging.
NUCLEO-CYTOPLASMIC PROTEIN PARTITIONING
Traffic of large proteins across the nuclear pore is mediated by karyopherins that recognize cargoes and mediate proper protein partitioning. Subcellular mispartitioning of proteins from dysregulated karyopherins is emerging as a key driver of age-related diseases, including many cancers and several neurodegenerative diseases. Our goals are to identify protein partitioning that protect cells from aging and to pharmacologically target karyopherins to foster cytoprotective nucleo-cytoplasmic partitioning.
LIPID REMODELING AND SIGNALING
Lipids have multiple roles in the cell, including membrane biology, metabolism and signaling. Lipid bilayers are essential components of organelles and the accumulation of damaged lipids is associated with accelerating aging and disease. Intracellular synthesis of lipids can drive lipid membrane renewal, but its role in aging is unclear. Our goals are to determine the contribution of lipids in organelle biogenesis and function as well as in autophagy and longevity-associated signaling.