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Professor of Pediatrics, Cell Biology and Physiology; Unit Leader Pathobiology

• Hematology and Oncology
• Pathobiology
• Guojun Bu Research Lab

Our laboratory is interested in the cell biology of intracellular protein trafficking. Our studies have been focused primarily on a large endocytic receptor, the low-density lipoprotein receptor-related protein (LRP). LRP is a multifunctional cell surface receptor, capable of binding and endocytosing over fifteen 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 also been extended to understanding the functions and cellular trafficking of other members of the LDL receptor family including LRP1B, megalin, apoE receptor 2, and LRP6. A 39-kDa receptor-associated protein (RAP) interacts with and antagonizes all ligand interactions with LRP. Physiologically, RAP is an endoplasmic reticulum (ER) chaperone for LRP. In addition to assisting receptor folding, RAP associates with LRP during its trafficking along the early secretory pathway to prevent premature interaction of ligands with the receptor. Currently, we are trying to define the precise role of RAP during the biogenesis of LRP and the mechanisms underlying these functions.

Another research area in my laboratory involves the analysis of LRP within the central nervous system. Three LRP ligands, apolipoprotein E (apoE), alpha₂-macroglobulin, and amyloid precursor protein (APP), have been shown to participate in the pathogenesis of Alzheimer's disease (AD). Our goal in this area is to examine how LRP expression is regulated within the CNS, and how its regulation in turn affects the catabolism and function of these ligands and amyloid peptide during aging and AD.

Education

• B.S., Beijing Normal University, 1985
• Ph.D., Virginia Tech, 1990

Training

• Postdoctoral Fellowship, Department of Pediatrics, Washington University School of Medicine, 1990-1994

Honors

• American Heart Association Missouri Affiliate Fellow, 1991-1993
• National Institutes of Health, National Research Service Award, 1993-1994
• Faculty Scholar Award, Alzheimer's Association, 1995-1998

Selected Publications

1. Liu Q, Zerbinatti CV, Zhang J, Hoe H-S, Wang B, Cole SL, Herz J, Muglia L, Bu G: Amyloid precursor protein regulates brain apolipoprotein E and cholesterol metabolism through lipoprotein receptor LRP1. Neuron; In press.

2. Zerbinatti CV, Wahrle SE, Kim H, Cam JA, Bales K, Paul S, Holtzman DM, Bu G: Effects of LRP and apoE on intraneuronal Abeta in PDAPP mice. J Biol Chem 2006; 281:36180-36186. [ pubmed ]

3. Van Kerkhof P, Lee J, McCormick L, Tetrault E, Lu W, Schoenfish M, Oorschot V, Strous GJ, Klumperman J, Bu G: Sorting nexin 17 facilitates LRP recycling in the early endosome. EMBO J 2005, 24:2851-2861. [ pubmed ]

4. Li Y, Chen J, Lu W, McCormick LM, Wang J, Bu G: Mesd binds to mature LDL receptor-related protein-6 and antagonizes ligand binding. J Cell Sci 2005; 118:5305-5314. [ pubmed ]

5. Cam JA, Zerbinatti CV, Li Y, Bu G: Rapid endocytosis of the LDL receptor-related protein modulates cell surface distribution and processing of the beta-amyloid precursor protein. J Biol Chem 2005; 280:15464-15470. [ pubmed ]

6. Li Y, Lu W, He X, Schwartz AL, Bu G: LRP6 expression promotes cancer cell proliferation and tumorigenesis by altering beta-catenin subcellular distribution. Oncogene 2004; 23:9129-9135. [ pubmed ]

7. Zerbinatti CV, Wozniak DF, Cirrito J, Cam JA, Osaka H, Bales KR, Zhuo M, Paul SM, Holtzman DM, Bu G: Increased soluble amyloid-beta peptide and memory deficits in amyloid model mice overexpressing the LDL receptor-related protein. Proc Natl Acad Sci USA 2004; 101:1075-1080. [ pubmed ]