Jianjun Wang, Ph.D.

Research in our laboratory focuses on two major human diseases: heart disease and Alzheimer's disease. We are using structural biology, molecular biology, protein chemistry, biophysics and protein engineering techniques in our research. Our research objectives are centered on solving the structures of several critical proteins that are involved in cholesterol transport in the peripheral tissues and in the brain. Apolipoprotein E (apoE) and LDL receptor are the two critical proteins that are involved in the LDL receptor mediated endocytosis of LDL particles. One project in our lab is to study apoE/LDL receptor interactions. ApoE also interacts with amyloid peptide (Abeta 4) and is the only confirmed risk gene for Alzheimer's disease. Our second project is to study apoE/Abeta 4 peptide interactions. This project also includes screening small organic compounds for drug discovery in treating Alzheimer's disease patients. In the HDL assembly and transport, several proteins play important roles, including apolipoprotein A-I (apoAI), ABC-AI, LCAT and the HDL receptor (SR-BI). ApoAI is especially critical for HDL formation, maturation and transport. Our third project is to determine the HDL structures, including lipid-free apoAI, prebeta-HDL, discoidal HDL and spherical HDLs. Our preliminary data demonstrated that we are able to determine the structures of lipid-free apoAI and prebeta-HDL. Future studies will include ABC-AI, LCAT and SR-BI. Since a low level of plasma HDL and a compromised HDL function are the common thread of metabolic disorders/diseases including: atherosclerosis, diabetes, obesity, stroke, and Alzheimer's disease, the results obtained from these studies should have significant implications for the design of new medicines to treat these metabolic disorders/diseases.

Yonghe Li, Jianglei Chen, Wenyan Lu, Lynn M. McCormick, J. Wang, and Guojun Bu (2005). Mesd binds to mature LDL receptor-related protein-6 and antagonizes ligand binding. J. Cell Biol., Accepted for publication.

Xu C, Sivashanmugam, A, Hoyt D & Wang J (2005). A complete Backbone Assignment of the human apolipoprotein E LDL-receptor-binding domain. J. Biomol-NMR, Accepted for publication.

Ramirez-Arcos S., Greco, V., Douglas, H. Tessier, D., Fan, D.,Wang, J and Dillon, J.R. (2004). Four Conserved Glycines in the C-terminus of MinC are Essential for Protein Functionality. J Bacteriol. 186:2841-2855.

Fan. D., Korando L., Li Q. & Wang J. (2004). A monomeric apoE C-terminal domain that is biologically active. Biochemistry 43:5055-5064.

Lapierre L., Yao Z., Currie D. L. Wang, J. and McLeod R. S. (2004). Structure-function analysis of the β1 domain of human apolipoprotein B. Evidence for sequence-specific ubiquitination J Lipid Res. 45:366-77.

Fan D. Zhen Y, Yang D. & Wang, J. (2003). NMR structure of an exchangeable apolipoprotein - L. migratoria apoLp-III. J. Biol. Chem. 278:21212-20.

Wang, J., Sykes, B.D. and Ryan, R.O. (2002). Structural Basis of Reversible Lipoprotein-binding Activity of Exchangeable Apolipoproteins. Proc. Natl. Acad. Sci. U.S.A. 99, 1188-1193.