SEMINAR Department of Biomedical Engineering From Glycans to Lipids and Vice Versa Wednesday, April 22 1034 Emerging Technologies Building 9:10 a.m. Low-density lipoprotein (LDL) has a role in aging process, including vascular senescence. However, not all LDL particles are pathogenic, and the culprit LDL entity remains to be identified. In our search for the culprit LDL, we have isolated a highly electronegative entity, L5, from human plasma LDL subfractions (L1-L5) resolved by using anionexchange chromatography. From evidence based on in vitro, in vivo, and human studies, we have demonstrated L5’s pro-senescent, inflammatory, Chu-Huang (Mendel) Chen, atherosclerotic, and thrombotic properties, which are not seen in L1-L4. Ph.D.. M.D. Chemical analysis has revealed that L5 carries excessive apolipoproteins (apoE, A1, CII, CIII, (a), J) in addition to apoB100, which is the only protein Director, Vascular and Medicinal in the least electronegative LDL, L1. Further analysis has shown consistent Research, Texas Heart Institute glycosylation on certain residues of both apoE and apoB100 in L5 particles. The associated conformational changes result in hindrance of L5 docking Chairman, Research Advisory to the normal LDL receptor, forcing an increased residence time of the Committee, New York Heart Research Foundation L5 particles in circulation. The apoB100 molecule in L5 also possesses a prominent SMase-like activity. Consequently, L5 is not only a ceramideChair Professor of Medicine, Kaohsiung rich lipoprotein but can also induce excessive ceramide production in ECs Medical University through SMase-like activity. Additionally, our preliminary studies suggest that L5 is able to glycosylate transmembrane receptors, such as STRA6 (stimulated by retinoic acid 6). Because of STRA6’s role in transducing retinoic acid (vitamin A) signaling, its glycosylation by L5 impedes normal cellular function, adding to complications in disease patterns, as in type 2 diabetes. Thus, L5 is both a glycan receiver and glycan donor/catalyzer. Glycan-lipid interactions are likely to have important biological and clinical implications. Extensive investigations are warranted to delineate the underlying mechanisms to advance our understanding of lipid-associated diseases and to disclose new targets for treatment. Chu-Huang (Mendel) Chen Dr. Chen received his M.D. from Kaohsiung Medical University, Taiwan, and Ph.D. in Physiology from Texas Tech University. He received his residency training both in Taiwan and the United States, and Cardiology Fellowship at Baylor College of Medicine. Dr. Chen and his teams have focused their research on the atherogenicity of chargedefined lipoproteins and have demonstrated in a series of publications the chemical and functional properties of electronegative lipoprotein (including LDL, VLDL, HDL) subfractions isolated by using anion-exchange chromatography. They have published more than 120 articles, many of them in prestigious medical and scientific journals, describing how tiny lipid particles may benefit health and how, when they are abnormal, can cause harm. Recently, they have focused on the interactions between lipids and glycans, and the biological impact of these interactions. In addition, Dr. Chen is involved in nationwide, NIH-sponsored clinical studies in the United States. To help promote lipid research in Taiwan, Dr. Chen travels to his homeland and has organized a research network comprising internationally renowned experts from the United States and Japan to expedite the growth in a profound manner.