Dr. Bu's laboratory investigates the role of the low-density lipoprotein receptor (LDLR) family and its ligands in the central nervous system and in the pathogenesis of Alzheimer's disease. LDLR family members, including low-density lipoprotein receptor-related protein 1 (LRP1) and LDLR itself, regulate the metabolism of amyloid-beta (Abeta) peptide and apolipoprotein E (apoE).
While Abeta is the primary toxic molecule in Alzheimer's disease-affected brains and a major component of amyloid plaques, an isoform of apoE — apoE4 — is a strong risk factor for late-onset Alzheimer's disease. Dr. Bu's laboratory is investigating several major pathways in the brain that modulate its metabolism of Abeta and apoE, specifically focusing on LRP1 and LDLR. The lab's ultimate goals include understanding why apoE4 is a strong risk factor for Alzheimer's disease, and defining novel methods to diagnose and treat the disease.
Understanding the roles of LDLR family members in tumorigenesis is another active area of research within Dr. Bu's lab. The lab has recently shown that two LRPs play critical roles in tumorigenesis, particularly in breast and brain tumors. Dr. Bu's goals related to this include examining how modulation of LRP expression influences tumor development and progression in vitro and in vivo, and testing the effects of LRP antagonists in cancer development and progression.