Research Abstract:
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 (LRP1), 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 LRP1 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. Among them, LRP1B resembles LRP1 in structure but endocytoses ligands with a significantly slower rate. We are currently conducting research aimed at understanding how LRP1B expression modulates tumor cell behavior and how it functions as a tumor suppressor. LRP6 is a co-receptor for the Wnt signaling pathway. We are currently examining how LRP6 modulates Wnt signaling and what is its role in breast cancer pathogenesis.
Another research area actively investigated in my laboratory is defining the roles of LRPs in the central nervous system and in the pathogenesis of Alzheimer’s disease (AD). Three LRP1 ligands, apolipoprotein E (apoE), amyloid precursor protein (APP), and amyloid abeta-peptide play central roles in AD. Our goal in this area is to examine how LRPs regulate cellular trafficking and processing of APP, and how their expression and function impact the metabolism of amyloid beta-peptide and apoE/cholesterol during aging and AD. Several animal models are being used for this research area.
Selected Publications:
Bu G. Apolipoprotein E and its receptors in Alzheimer's disease: pathways, pathogenesis and therapy. Nat Rev Neurosci 2009 10: 333-344.
Song H, Li Y, Lee J, Schwartz AL, Bu G. Low-density lipoprotein receptor-related protein 1 promotes cancer cell migration and invasion by inducing the expression of matrix metalloproteinases 2 and 9. Cancer Res 2009 69: 879-886.
Cirrito JR, Kang J-E, Lee J, et al.. Endocytosis is required for synaptic activity-dependent release of amyloid-beta in vivo. Neuron 2008 58: 42-51.
Liu Q, Zerbinatti CV, Zhang J, et al.. Amyloid precursor protein regulates brain apolipoprotein E and cholesterol metabolism through lipoprotein receptor LRP1. Neuron 2007 56: 66-78.
Van Kerkhof P, Lee J, McCormick L, et al.. Sorting nexin 17 facilitates LRP recycling in the early endosome. EMBO J 2005 24: 2851-2861.
Last Updated: 08/12/2009 |