Liang-Yin (Maurice) Ke
Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University
Lipid Science and Aging Research Center (LSARC), Kaohsiung Medical University
Center for Lipid Biosciences (CLB), Kaohsiung Medical University Hospital
Tel: 886-7-3121101 #2297
National Cheng-Kung University: Bachelor / Medical Laboratory Science and Biotechnology
Kaohsiung Medical University: Master / Graduate Institute of Medicine, College of Medicine
Kaohsiung Medical University: PhD / Graduate Institute of Medicine, College of Medicine
Pre-Doctoral Fellow, Athero & Vascular Medicine, Baylor College of Medicine, Texas, USA
Pre-Doctoral Fellow, Vascular and Medicinal Research, Texas Heart Institute, Texas, USA
Professional Working Experience
1994.07-1996.05 Medical Technologist, National Military Hospital
1996.06-1996.12 Medical Technologist, Great East Hospital
1996.12-2005.02 Medical Technologist, Division of Infectious Disease, Department of Internal Medicine, Kaohsiung Medical University Hospital
2005.03-2014.07 Department of Laboratory Medicine, Kaohsiung Medical University Hospital
2014.07-2018.02 Assistant Professor, Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University
2012.12-today Center for Lipid Biosciences, Kaohsiung Medical University Hospital
2014.07-today Lipid Science and Aging Research Center, Kaohsiung Medical University
2018.02-today Associate Professor, Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University
Proteomics, Lipidomics, Molecular Biology and Molecular Diagnostics
2015 KMU Excellent homeroom teacher (校級績優導師)
2016 KMU Outstanding Faculty Research Award (研究傑出教師/研究成果績優獎)
2017 Finalist of the Young Investigator Competition of the University of Cologne – Kaohsiung Medical University Joint Symposium
Inventions and patents
Patent No. I359196:用於檢測伯氏疏螺旋體菌致病性菌株的引子對、檢驗套組以及方法Early detection of Borrelia burgdorferi sensu lato, the PCR primer pair and diagnostic method. (50%)
Patent No. I580782: 去除陰電性低密度脂蛋白之生化反應材料與裝置以及體外處理血液或血漿以去除其中陰電性低密度脂蛋白的方法 (25%)
Patent No. CN106434619A: 生化反应材料与装置以及体外处理血液或血浆的方法(25%)
Patent No. US20170044516A1: Biochemistry reactive material and device for eliminating low-density lipoprotein (LDL) and method for treating blood or plasma ex vivo to eliminate low-density lipoprotein therein (25%)
Patent No. US20150148410A1: Identification of specific apolipoprotein epitopes on circulating atherogenic LDL (50%)
*: corresponding author
A. Flowchart for isolating atherogenic lipoproteins
B. Flowchart for studying proteomics and Lipidomics
1. Enhanced sphingomyelinase activity in apolipoprotein B100 contributes to the atherogenicity of electronegative LDL. J Med Chem. 2016 Feb 11;59(3):1032-40.
Sphingomyelinase (SMase) catalyzes the degradation of sphingomyelin to ceramide. In patients with metabolic syndrome or diabetes, circulating plasma ceramide levels are significantly higher than in normal individuals. Our data indicate that electronegative low-density lipoprotein (LDL) shows SMase activity, which leads to increased ceramide levels that can produce pro-inflammatory effects and susceptibility to aggregation. According to sequence alignment and protein structure predictions, the putative catalytic site of SMase activity is in the α2 region of apoB-100. To identify specific post-translational modifications of apoB100 near the catalytic region, we performed data-independent, parallel-fragmentation liquid chromatography/mass spectrometry (LC/MSE), followed by data analysis with ProteinLynx GlobalServer v2.4. Results showed that the serine of apoB100 in electronegative LDL was highly O-glycosylated, including S1732, S1959, S2378, S2408 and S2429. These findings may support the changing of α-helix/β-pleated sheets ratio in protein structure analysis. Further study is necessary to confirm the activation of SMase activity by electronegative LDL.
2. The Underlying Chemistry of Electronegative LDL's Atherogenicity. (First author). Curr Atheroscler Rep. 2014 Aug;16(8):428)
Electronegative low-density lipoprotein (LDL) found in human plasma is highly atherogenic and is elevated in individuals with increased cardiovascular risk. In this review, we summarize the available data regarding the elevation of electronegative LDL in the plasma of patients with various diseases. In addition, we discuss the harmful effects and underlying mechanisms of electronegative LDL in various cell types. We also highlight the known biochemical properties of electronegative LDL that may contribute to its atherogenic functions, including its lipid and protein composition, enzymatic activities, and structural features. Given the increasing recognition of electronegative LDL as a potential biomarker and therapeutic target for the prevention of cardiovascular disease, key future goals include the development of a standard methodology for the detection of electronegative LDL that can be used in a large-scale population survey and the identification and testing of strategies for eliminating electronegative LDL from the blood.
3. Highly electronegative LDL from patients with ST-elevation myocardial infarction triggers platelet activation and aggregation. (Blood. 2013;122:3632-3641).
We provide evidence that plasma levels of L5—the most electronegative and atherogenic subfraction of low-density lipoprotein—are drastically elevated in patients with ST-elevation myocardial infarction (STEMI). Furthermore, we show that when L5 isolated from the plasma of STEMI patients was injected into the tail vein of mice, it induced platelet activation and shortened the tail-bleeding time. These results indicate that L5 is prothrombotic, which was further demonstrated by the ability of L5 to increase tissue factor and P-selectin expression on endothelial cells, enhance platelet aggregation, and promote platelet–endothelial cell interactions. We also showed that L5 enhanced ADP-induced platelet activation through the PAFR- and LOX-1–mediated PKCα signaling pathway. Our findings strongly suggest that L5 may be a key factor in promoting acute thrombosis that leads to STEMI.
4. Chemical composition-oriented receptor selectivity of L5, a naturally occurring atherogenic low-density lipoprotein. (Pure Appl Chem. 2011;83(9).
Analysis with SDS-PAGE and 2-dimensional electrophoresis showed that the protein framework of L1 was composed mainly of apolipoprotein (apo) B100, with an isoelectric point (pI) of 6.620. There was a progressively increased association of additional proteins, including apoE (pI 5.5), apoAI (pI 5.4), apoCIII (pI 5.1), and apo(a) (pI 5.5), from L1 to L5. LC/MSE was used to quantify protein distribution in all subfractions. On the basis of weight percentages, L1 contained 99% apoB-100 and trace amounts of other proteins. In contrast, L5 contained 60% apoB100 and substantially increased amounts of apo(a), apoE, apoAI, and apoCIII. The compositional characteristics contribute to L5's electronegativity, rendering it unrecognizable by LDLR. Thus, the chemical composition-oriented receptor selectivity hinders normal metabolism of L5, enhancing its atherogenicity through LOX-1.
5. Vascular progenitor cells in diabetes mellitus: roles of Wnt signaling and negatively charged low-density lipoprotein. (Chen CH, Dixon RA, Ke LY, Willerson JT. Circ Res. 2009 May 8;104(9):1038)
Expression of miR-8 potently antagonizes Wnt signaling, both by inhibiting Wnt-Fz interaction on the plasma membrane and by reducing TCF protein intracellularly. Additionally, miR-15a and miR-16-1 can also antagonize Wnt signaling, and reduction of these microRNAs promotes growth of prostate cancer cells. Thus, the role of Wnt signaling in EC or vascular PC activity is not totally clear at this time, and uncontrolled stimulation of this pathway may invite dangerous consequences. These considerations, including how L5 may counteract the CD133+ PC and Wnt interactions, are schematically summarized in the Figure.
20180723 Students' English presentation, before internship program in Waseda University (Japan) and Cologne University (Germany)
20180723 Dissertation Defense (with Associate Professor An-Sheng Lee from Mackay Medical College)
20180708-0713 Summer Workshop
Professor Chu-Huang (Mendel) Chen
Professor Gopal K. Marathe
Professor Ming-Shi Shiao
Professor Gopal K. Marathe
Professor Chuan-Fa Chang （張權發）from National Cheng Kung University
Associate Professor Liang-Yin (Maurice) Ke
20180706 Students' presentation to professor Gopal K. Marathe from Mysore University, India.
20180119-0209 University of Cologne, Germany
20171108-15 American Heart Association 2017 Scientific Secessions
20171103 【專題演講】Precision Diagnosis with Ultrasensitive ELISA and Surface-enhanced Roman Spectroscopy
20171012 【專題演講】「An Omics Avenue to Precision Medicine」
20170807 【專題演講】「Biology of a Lectin-Like Receptor」
20170706 【專題演講】「A Look into the Secrets of Aging and Metabolic Disorders from a Metabolomic Window」邀請蕭明邀請蕭明熙教授、Fionn Quinlan專題演講
20170616 【專題演講】「Genetic, structural and functional studies of cardiac gap junctions 」研討會邀請 Western University London Professor Donglin Bai專題演講「Connexin Molecules in Heart Rhythm Synchronization」
20170602 White Coat Ceremony
20170518 Invite Prof. Tatsuya Sawamura from Shinshu University, Japan
20170516-0518 Invite Prof. Kazushi Motomura from Nagasaki University, Japan
20161017 Dinner party with Dr. Günter Schwarz, (University of Cologne, Köln)
20160628 Dinner party with Rena and Chihiro, two students from the School of Medicine, Shinshu University
20160624 Students' Party at PERFUME DANCE CAFE
20160607-0609 The 2016 Alzheimer's disease congress
20160309-0311 IBMS-KMU Joint Symposium
20160304 KMU-Waters Symposium on Metabolomics and Aging
20160129 CLB Happy-New-Year Party
20151216 KMU-Waters Symposium
20151109 American Heart Association Scientific Sessions in Orlando, FL, November 7–11, 2015.
20151028-1030 Kazushi MOTOMURA Collaborative teaching on "Biotechnology"
20150825 Mamiko Koshiba, Ph.D. from Saitama Medical University
20150518 Lee Jun C. Wong's talk on NGS
20150323 International Symposium: New Era of Lipid and Glycomedicine Research
20141225 X'mas Party