Guojun Bu, Ph.D.
Guojun Bu, Ph.D.
Our laboratory investigates the roles of low-density lipoprotein receptor (LDLR) family and their ligands in the central nervous system and in the pathogenesis of Alzheimer's disease (AD).
LDLR family members, including LDL receptor-related protein 1 (LRP1) and LDLR, regulate the metabolism of amyloid-β (Aβ) peptide and apolipoprotein E (apoE). While Aβ is the primary toxic molecule in AD brains and a major component of amyloid plaques, an isoform of apoE (apoE4) is a strong risk factor for late-onset AD. Our laboratory is dissecting several major pathways in the brain that modulate the brain metabolism of Aβ and apoE, with specific focus on LRP1 and LDLR.
We utilize genetically altered mice, including conditional knockout and transgenic mouse models, to study the functions of apoE and apoE receptors in brain lipid metabolism, signal transduction, synaptic transmission, neuronal viability and memory. Primary neurons are also used to study the underlying cellular mechanisms. Several new mouse models have been developed in our laboratory to uncover the apoE isoform-specific effects in an age-dependent manner and to determine how apoE receptors further modulate these events.
Our ultimate goals are to understand why apoE4 is a strong risk factor for AD and to define novel methods to diagnose and treat AD.
Another research area that we actively investigate is to understand the roles of LDLR family members in tumorigenesis. We recently have shown that two LRPs play critical roles in tumorigenesis, particularly in breast and brain tumors. Specifically, LRP6-modulated Wnt/β-catenin signaling is up-regulated in a breast tumor subset and is a target for therapy, whereas increased LRP1 expression in glioblastoma promotes tumor cell migration and invasion by up-regulating the expression of several metalloproteases.
Thus our goals are to examine how modulation of LRP expression influences tumor development and progression in vitro and in vivo, and to test the effects of LRP antagonists in cancer development and progression.
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