LDL receptor family members in human disease

Our laboratory is interested in receptor-mediated endocytosis, signal transduction, and intracellular protein trafficking. Our studies have been focused on members of the low-density lipoprotein (LDL) receptor family. One member of the family, the LDL receptor-related protein (LRP), is a multifunctional cell surface receptor capable of binding and endocytosing over 30 ligands. We are interested in identifying both trans- and cis-elements within the cytoplasmic tail of LRP that govern its trafficking and signaling. Our recent studies have been extended to understanding the biology of other members of the family including LRP1B, megalin, apoE receptor 2, and LRP6.

Another research area actively investigated in my laboratory is defining the roles of LRPs within the central nervous system and in the pathogenesis of Alzheimer’s disease (AD). Three LRP ligands, apolipoprotein E (apoE), alpha-2-macroglobulin, and amyloid precursor protein (APP), have been shown to play roles in AD. Our goal in this area is to examine how LRPs regulate cellular trafficking and processing of APP, and how their expression impacts the catabolism of amyloid beta-peptide during aging and AD. Several animal models are being used for this research area.