Biography
Research Interests:
Elevated plasma level of cholesterol is a risk factor to developing atherosclerosis, a leading cause to cardiovascular diseases, such as heart attacks and strokes. To maintain cholesterol balance, an equivalent amount of cholesterol must be eliminated from cells and tissues, and excess cholesterol in cells is transported to extracellular acceptors in the circulation by lipid transporter-mediated cholesterol efflux. The predominant cholesterol-lowering medication is to inhibit de novo cholesterol synthesis or increases cholesterol uptake via LDL, the treatment to the deficiency in HDL metabolism or cholesterol efflux system are limited. To universally prevent cholesterol build-up in the tissues, there is urgent need for drug development targeting cholesterol upload to circulating HDL to control the systemic cholesterol level and treat cardiovascular diseases.
Lipid transport membrane proteins are responsible for maintaining the structural integrity of mosaic bilayers and cellular functions by regulating translocation of sterols and phospholipids within lipid bilayers. Dr. Lee’ recent groundbreaking discovery in solving the first crystal structure of a human ABC sterol transporter establishes a molecular framework to structure-function relationship on cholesterol efflux ABC transporters. Dr. Lee’s laboratory will use structural biology, biophysics and membrane protein biochemistry as the primary approaches, and his research program seeks to i) elucidate the catalytic and the transport mechanisms of ABC sterol and lipid transporters, ii) characterize the specific role of ABC transporters in lipid transport and lipoprotein formation, and iii) define the molecular events that can be targeted for pharmaceutical manipulation.
Selected Publications:
- Lee, J.-Y. and Rosenbaum, D.M. Transporters Revealed. Cell 168(6): 951-953 (2017).
- Lee, J.-Y., Rosenbaum, D.M. and Hobbs, H.H. Structural Role of ABCG5/ABCG8 in Sterol Transport. Biophys. J. 112(3): 22a (2017).
- Lee, J.-Y., Kinch, L.N., Borek, D.M., Wang, J., Wang J., Urbatsch, I.L., Xie, X.-S., Grishin, N.V., Cohen, J.C., Otwinowski, Z., Hobbs, H.H. and Rosenbaum, D.M. Crystal Structure of the Human Sterol Transporter ABCG5/ABCG8. Nature 533(7604): 561-564 (2016).
- Johnson, B.J.H., Lee, J.-Y., Pickert, A., and Urbatsch, I.L. Bile Acids Stimulated ATP Hydrolysis in the Purified Cholesterol Transporter ABCG5/G8. Biochemistry, 49(16): 3403-3411 (2010).
- Harvey, B., Lee, J.-Y., and Urbatsch, I.L. Encyclopedia of Molecular Mechanisms of Disease: Sitosterolemia. Springer Heidelberg Germany, Pt 19: 1941-3 (2009).
- Lee, J.-Y., Urbatsch, I.L., Senior, A.E., and Wilkens, S. Nucleotide-induced Structural Changes in P-glycoprotein Observed by Electron Microscopy. J. Biol. Chem. 283(9): 5769-79 (2008).
- Chloupková , M, Pickert, A., Lee, J.-Y., Souza, S., Trinh, Y.T., Connelly, S.M., Dumont, M.E., Dean, M., and Urbatsch, I.L. Expression of 25 Human ABC Transporters in the yeast Pichia pastoris and Characterization of the Purified ABCC3 ATPase Activity. Biochemistry, 46(27): 7992-8003 (2007).
- Lee, J.-Y., Urbatsch, I.L., Senior, A.E., and Wilkens, S. Projection Structure of P-glycoprotein by Electron Microscopy: Evidence for a Closed Conformation of the Nucleotide-Binding Domains. J. Biol. Chem. 277(42): 40125-31 (2002).