Nakamura T., Lapierre, L.R., Hansen, M. and Lipton S. (2016) The Neurobiology of aging: Free Radical Stress and Metabolic Pathways. Brocklehurst’s Textbook of Geriatric Medicine and Gerontology, 8th Edition.
The Lapierre laboratory uses a combination of biochemical, genetic and molecular approaches to study aging in a well-established aging research model, the nematode C. elegans. Our focus is to expand our understanding of the biology of aging by investigating the autophagy/lysosomal pathway, a central longevity mechanism.
Three major projects are being pursued in our laboratory:
1. 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.
2. Regulatory network of autophagy: Autophagy, the process of engulfing its own macromolecules using lipid membranes, leads to the degradation of damaged organelles 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.
3. 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.
NIA/NIH R01 AG051810
Regulation of the transcription factor HLH-30/TFEB in aging