Our laboratory is interested in
receptor-mediated endocytosis, signal transduction, and
intracellular protein trafficking. Our studies have been focusing
on members of the low-density lipoprotein (LDL) receptor family.
One member of the family, the LDL receptor-related protein 1
(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.
Guojun Bu, Ph.D. Professor of Pediatrics, and of Cell Biology and Physiology Washington University School of Medicine, CB 8208 McDonnell Pediatric Research Building 660 South Euclid Avenue St. Louis, Missouri 63110 E-mail:
Phone: 314-286-2860 Fax: 314-286-2894
SCHOOL OF MEDICINE
