Yu-Li Liu, Ph.D. Assistant Investigator Institute of Population Health Sciences E-mail: ylliou@nhri.org.tw Education Ph.D., East Tennessee State University, U.S.A., 1997 M.S., National Yang-Ming Medical College, Taiwan, 1987 Professional Experiences Research Associate, Division of Mental Health and Substance Abuse Research, National Health Research Institute, Taiwan Post-doctor, Department of Medical Research/Psychiatry, National Taiwan University Hospital, Taipei, Taiwan Clinical Researcher, Department of Education and Research Center, Shin Kong WHS Memorial Hospital, Taipei, Taiwan Research Interests Yu-Li's research interest is mainly in clinical psychiatric genetic research for schizophrenia. This includes the candidate genes screening, functional verification, and treatment monitoring. She had continually working with the molecular schizophrenia research team leading by Professor Hai-Gwo Hwu at National Taiwan University Hospital and National Taiwan College of Medicine for the psychopathological studies of novel schizophrenia candidate genes in the population of Taiwan. She joined the Division of Mental Health and Addiction Medicine, Institute of Population Health Sciences, NHRI since 2006 and embarked on the trip for Pharmacogenomic studies. She started these studies through establishing the therapeutic drug monitoring (TDM) system for antipsychotics of clozapine, then antidepressants of escitalopram (S-CIT) and paroxetine, and the recent build up of methadone enantiomer analyses with high performance liquid chromatography. Later on, she applied these results along with several clinical studies; the antidepressant study in collaboration with Professor Keh-Ming Lin, the antipsychotic clozapine study for refractory schizophrenia in collaboration with Dr. Sheng-Chang Wang, and addiction medicine of methadone replacement therapy for heroin addicts in collaboration with Professor Ing-Kang Ho. With 1
these intensive collaborations, she starts collecting information concerning the roles of these Pharmcodynamic and Pharmacokinetic genes as indicators for the treatment responses, the plasma concentrations and the side effects for different diseases. Research Activities & Accomplishment The research activities in Yu-Li's lab are gradually built up not only in the hardware, but also in the study projects conducting in her lab. Several research grants had input to this laboratory which make the team work and collaborations with different background of researchers become essential. The currently supported grants include the following. Therapeutic Drug Monitoring and Pharmacogenomics in Psychiatry This grant was supported from Department of Health. It was written in part to support the study of Taiwanese Psychiatric Research Network (TPRN). The therapeutic drug monitoring (TDM) system had established the standard analyses procedures for at least eight drugs and their metabolites. These drugs include antipsychotics of clozapine and aripiprazole, antidepressants of escitalopram and paroxetine, anxiolytics of venlafaxine, addictive medicine of methadone, buprenorphine and morphine. This study project also supported two clinical studies of both antidepressants and antipsychotics. The research results concerning these two studies are as following: In antidepressant study, the research team found genetic polymorphisms in CYP2C19 may be influencing S-CIT serum concentrations, and that specific CYP2D6 polymorphisms may be predicting patient treatment outcomes based on gene dosage analyses. This paper was just accepted by the journal of Pharmacogenomics. In antipsychotic study, genes from psychopathological screening may applied in this study. Interesting result concerning a candidate gene was found and the manuscript is currently under preparation. Liver cytochrome P-450 isozyme alterations after long-term maternal exposure under the morphine and environmental toxic substance.this study was designed co-adhesively with the other studies in our division to observe if prenatal morphine exposure may have effects on the CYP enzymatic expressions and activities on the postnatal offsprings. Further study on schizophrenia candidate gene CACNG2 This grant was supported from National Science Council. It is a study in 2
deciphering whether the genetic single nucleotide polymorphisms at the introns region are simply a marker or carrying a function. A Pharmacogenomic Study on Methadone Therapeutics This grant was supported by National Research Program for Genomic Medicine (NRPGM) launched by National Science Council as a national priority program. This project is still recruiting patients. However, the enantiomer quantitative method was established for methadone. A paper concerning the detail analyses were published at 2010 of Biomedical Chromatography. Honors & Awards Member of The Pharmacological Society in Taiwan 1. Licensed Pharmacist of Taiwan Publications/ including books, chapters, journal articles Peer-Reviewed Articles 1. Sun, HS, Fann, CSJ, Lane, HY, Chang, YT, Chang, C-J, Liu, YL, Yu, WY, Cheng, ATA. A functional polymorphism in the promoter region of the tryptophan hydroxylase gene is associated with alcohol dependence in one aboriginal group in Taiwan.. Alcohol. Clin. Exp. Res.. 29 (1):1-7, 2005. 2. Yue, CT, and Liu, YL. Fluoxetine increases extracellular levels of 3-methoxy-4- hydroxyphenylglycol in cultured COLO320 DM cells.. Cell Biochem.. Func23:109-114, 2005. 3. Liu, CM, Hwu, HG, Fann, SJ Cathy, Lin, CY, Liu, YL, Ou-Yang, WC, Lee, FCS. Linkage evidence of schizophrenia to loci near neuregulin 1 gene on chromosome 8p21 in Taiwanese families.. Am. J. Med. Genet B Neuropsychiatr. Genet.. 134(B):79-83, 2005. 4. Lin, HF, Liu, YL, Liu, CM, Hung, SI, Hwu, HG and Chen, WJ. Neuregulin 1 gene is associated with variations in perceptual aberration of schizotypal personality in adolescents.. Psychological Medicine. 35 (11):1589-1598, 2005. 5. Liu, YL, Fann, CSJ, Liu, CM, Chen, WJ, Wu, JY, Hung, SI, Chen, JH, Jou, YS, Liu, SK, Hwang, TJ, Hsieh, MH, Ou-Yang, WC, Chan, HY, Chen, JJ, Yang, WC, Lin, CY, Lee, SFC and Hwu, HG. A SNP Fine Mapping Study on Chromosome 1q42.1 Reveals Vulnerability Genes of GNPAT and DISC1 in Schizophrenia: Association with Impairment of Sustained Attention.. Biol. Psych.. 60:554-562, 2006. 6. Liu, YL, Fann, CSJ, Liu, CM, Wu, JY, Hung, SI, Chan, HY, Chen, JJ, Pan, CC, Liu, SK, Shieh, MH, Hwang, TJ, OuYang, WC, Chen, CY, Lin, JJ, Chou, FHC, Chueh, CM, Liu, WM, Tsuang, MM, Faraone, SV, Tsuang, MT, Chen, WJ, and Hwu, HG. Absence of significant associations between four AKT1 SNP markers 3
and schizophrenia in the Taiwanese population.. Psych. Gene.. 16(1):39-41, 2006. 7. Chu, CY, Liu, YL, Chiu, HC, Jee, SH. Dopamine-induced apoptosis in human melanocytes involves generation of reactive oxygen species.. Br. J. Derm.. 154:1071-1079, 2006. 8. Liu, YL, Fann, CSJ, Liu, CM, Wu, JY, Hung, SI, Chan, HY, Chen, JJ, Lin, CY, Liu, SK, Hsieh, MH, Hwang, TJ, Ou-Yang, WC, Chen, CY, Lin, JJ, Chou, FHC, Chueh, CM, Liu, WM, Tsuang, MM, Faraone, SV, Tsuang, MT, Chen, WJ, and Hwu, Hai-Gwo. Evaluation of RGS4 as a candidate gene for schizophrenia.. Am. J. Med. Genet B Neuropsychiatr. Genet.. 141 (4):418-20, 2006. 9. Liu, YL, Fann, CSJ, Liu, CM, Chang, CC, Wu, JY, Hung, SI, Liu, SK, Hsieh, MH, Hwang, TJ, Chan, HY, Chen, JJ, Faraone, SV, Tsuang, MT, Chen, WJ, and Hwu, HG. No Association of G72 and D-Amino Acid Oxidase Genes with Schizophrenia.. Schizophr. Res.. 87:15-20, 2006. 10. Liu, CM, Liu, YL, Fann, CSJ, Yang, WC, Chen, WJ, Chueh, CM, Liu, WM, Liu, CC, Hsieh, MH, Hwang, TJ, Faraone, SV, Tsuang, MT, Hwu, HG. No Association Evidence between schizophrenia and Dystrobrevin-binding protein 1 (DTNBP1) in Taiwanese families.. Schizophr. Res.. 93:391-398, 2007. 11. Liu, CM, Liu, YL, Fann, CSJ, Chen, WJ, Chen, CH, Jou, YS, Ou-Yang, WC, Chan, HY, Chen, JJ, Liu, SK, Hsieh, MH, Hwang, TJ, Faraone, SV, Tsuang, MT and Hwu, HG. Association Evidence of Schizophrenia with Distal Genomic Region of NOTCH4 in Taiwanese families..gene Brain and Behavior.. 6(6):497-502, 2007. 12. Liu, YL, Fann, CSJ, Liu, CM, Chang, CC, Yang, WC, Wu, JY, Hung, SI, Chan, HY, Chen, JJ, Hsieh, MH, Hwang, TJ, Faraone, SV, Tsuang, MT, Chen, WJ and Hwu, HG. HTF9C Gene of 22q11.21 Region Associates with Schizophrenia Having Deficit Sustained Attention.. Psych. Gen.. 17(6):333-338, 2007. 13. Liu, YL, Fann, CSJ, Liu, CM, Yang, WC, Hung, SI, Yu, SL, Hwang, TJ, Shieh, MH, Liu, CC, Tsuang, MM, Wu, JY, Jou, YS, Faraone, SV, Tsuang, MT, Chen, WJ, and Hwu, HG. More evidence supports the association of PPP3CC with schizophrenia.. Mol. Psychiatry.. 12(10):966-974, 2007. 14. Hsu, PC, Yang, UC, Shih, KH, Liu, CM, Liu, YL, and Hwu, HG. A protein interaction based model for schizophrenia study. BMC Bioinformatics. 9 (Suppl 12):S23-, 2008. 15. Liu, YL, Fann, CSJ, Liu, CM, Chen, WJ, Wu, JY, Hung, SI, Chen, CH, Jou, YS, Ou-Yang, WC, Chan, HY, Chen, JJ, Lin, CY, Lee, SFC and Hwu, HG. RASD2, MYH9, and CACNG2 Genes at Chromosome 22q12 Associated with the Subgroup of Schizophrenia without Deficit in Sustained Attention and in Executive Function.. Biol. Psychiatry. 64(9):789-796, 2008. 4
16. Chien, YL, Liu, CM, Fann, CSJ, Liu, YL, Hwu, HG. Association of the 3 region of COMT with schizophrenia in Taiwan.. J. Formos. Med. Assoc.. 108(4):301-309, 2009. 17. Lin, SH, Liu, CM, Liu, YL, Fann, CSJ, Hsaio, PC, Wu, JY, Hung, SI, Chen, CH, Jou, YS, Liu, SK, Hwang, TJ, Hsieh, MH, Chang, CC, Yang, WC, Lin, JJ, Chou, FHC, Faraone, SV, Tsuang, MT, Hwu, HG and Chen, WJ. Clustering by neurocognition for fine-mapping of the schizophrenia susceptibility loci on chromosome 6p.. Gene, Brain and Behavior. 8:785-794, 2009. 18. Liu, YL, Liu, CM, Tien, HF, and Hwu, HG. Screening of Balanced Translocation t(1;11)(q42.1;q14.3) in the Genomic DNA Samples of Schizophrenia.. J. Formos. Med. Assoc..108(7):587-591, 2009. 19. Tsai, MH, Lin, KM, Hsiao, MC, Shen, WW, Lu, ML, Tang, HS, Fang, CK, Wu, CS, Lu, SC, Liu, SC, Chen, CY, Liu, YL. Antidepressant escitalopram metabolism and cytochrome P-450 isozymes genetic polymorphisms.. Pharmacogenomics.. :-, 2010. 20. Wang, SC, Ho, IK, Wu, SL, Liu, SC, Kuo, HW, Lin, KM, Liu, YL. Development of a Method to Measure Methadone Enantiomers and its Metabolites without Enantiomer Standard Compounds for the Plasma of Methadone Maintenance Patients.. Biomed. Chromatography.. :-, 2010. 21. Liu, YL, Liu, CM, Fann, CSJ, Yang, WC, Chen, YH, Tseng, LT, Liu, SK, Hsieh MH, Hwang, TJ, Chan, HY, Chen, JJ, Chen, WJ, and Hwu, HG. Genetic variant of IL-6 and its receptor are not associated with schizophrenia in Taiwan.. Neurosci. Letter. :-, 2010. Abstracts 1. Liu, YL*, Liu, CM, Fann, CSJ, Liu, TT, Tsai, SF, Yang, UC, Hsu, PC, Yang, WC, Wen, CC, Hwu, HG (2009) The significant genetic regions of schizophrenia susceptibility gene, calcium channel, voltage-dependent, gamma subunit (CACNG2). 17th World Congress on Psychiatric Genetics Abstract P205. 2.Tsai, MH, Lin, KM, Hsiao, MC, Shen, WW, Lu, ML, Tang, HS, Fang, CK, Wu, CS, Lu, SC, Liu, SC, Liu, YL* (2009) Cytochrome P-450 isozyme 2C19 genetic polymorphisms are associated with plasma concentrations of Escitalopram. The 11th International Congress of Therapeutic Drug Monitoring and Clinical Toxicology. Abstract P524. 3.Liu, YL*, Wang, SC, Liu, SC, Kuo, HW, Lin, KM, Ho, IK (2009) HPLC analysis the enantiomers of methadone and its metabolite from plasma of methadone maintenance patients. The 12th Society of Chinese Bioscientists in America (SCBA) symposium Abstract P245. 4.Liu, YL*, Liu, SC, Kuo, HW, Lin, KM, Ho, IK (2009) HPLC analyses 5
differentiate R-form from S-form enantiomers of me Patents N/A 6