Dedicated research associate with more than 10 years’ pharmaceutical R&D experience in the field of drug metabolism, pharmacokinetics, and bioanalysis. Extensive experience in in vitro assay development for mechanistic ADME studies, and proficient in bioanalytical and pharmacokinetic analysis to support discovery and early development projects. Ability to manage multiple tasks independently and efficiently, and highly motivated to learn new technologies.
SUMMARY OF QUALI ICATIONS AND SKILLS
• Extensive experience in setting up and running various enzymatic and cell-based assays for high throughput and mechanistic ADME studies.
• Good understanding of pharmacokinetics and able to conduct basic PK analysis to support projects.
• Solid knowledge and extensive hands on experience in developing, validating, and implementing bioanalytical assays using LC-MS/MS (sciex 5000), Q-TRAP, LTQ systems and other bioanalytical methods (UV, fluorescence, etc.)
• Highly skilled in various software products including: Analyst, SoftMax Pro, biobook, Windolin, LighSight™ Software 2.0 (AB SCIEX), Xcalibur, GraphPad. Microlab STAR, ISIS draws. Rapid.
• Well versed in 96-well plate extraction techniques and automation (Hamilton Biomek, Tecan /Evo).
• Good organizational, record keeping, presentation, communication skills and team player.
• Proficient in following GLP, SOPs and FDA guidelines.
Principal Research Associate – Roche Nutley 2009 - present
Primary responsibilities In vitro ADME assays:
Microsome and hepatocyte metabolism, induction, protein binding, CYP450 inhibition and TDI.
• Conducted rapid equilibrium dialysis (RED) assay to determine microsomal binding.
Optimized TRANSIL high sensitivity protein binding assay and TRANSIL XL liver binding in support of drug discovery projects.
• In Vitro induction, RNA purification with MagMAX, mRNA reverse to cDNA
Real-time PCR technologies (especially Taq-Man).
• Supported internal projects through routine microsomal/S9 metabolic stability and plasma/blood stability assays.
• Conducted specialized subcellular fraction incubations to understand and improve IVIVC to allow for the most effective use of departmental resources.
• Contributed to the development of automated methods for in Vitro assay using Hamilton systems. Input has been indispensable during design, testing & troubleshooting of these assays.
• Key user for ABI Sciex 5000, including regular maintenance, calibration checks, and troubleshooting
Research Associate III, DMPK - Roche Palo Alto 2002 - 2009
PK and project support
• Worked with DMPK project leaders to support PK studies for lead molecules as well as back-up compounds.
• Planned and scheduled rodent and non-rodent PK studies with in vivo group. Wrote and archived protocols in the study scheduling system. Coordinated with formulation group for dose preparation.
• Processed and analyzed samples from PK studies using LC-MS/MS and conducted PK data analysis using in-house templates. Prepared PK data summaries for DMPK project leader and wrote bioanalytical report for PK studies.
• Coordinated and provide PK support for pharmacology studies, and developed and validated analytical methods to enable plasma sample analysis for range-finding toxicology studies.
• Prepared SOPs, protocols, and final technical reports for IND enabling study.
• Principal contributor in the establishment of HLM TDI screening and definitive (kinetic) assay. Key contributor to the establishment of human hepatocyte TDI assay to support TDI- based DDI prediction. Work included in a publication in DMD (co-author.
• Primary responsible for P450 phenotyping assay using HLM and recombinant P450s for lead compounds or project specific request. Made significant contributions to the establishment of ISEF scaling factor to enable early reaction phenotyping study and DDI prediction.
• Key member of investigative ADME group. Main contribution includes design and execution of non-routine investigational enzymology studies to address specific project related issues (e.g. induction of UGT/CYP enzymes in toxicology studies).
• Developed and validated analytical method for plasma and tissue sample analysis to support PK and range-finding toxicology studies.
• Expertise in method development using API Q-TRAP for the metabolism in vitro study.
• Expertise in troubleshooting and problem-solving with respect to bioanalytical methods and instrument applications.
Research Associate DuPont, Crop Protection - DE 2000-2002
• Assisted in developing an understanding to environmental fate characteristics of crop protection chemicals; determined the degradation rate of chemicals in soil, water and plants.
• Determined physical/chemical properties using analytical techniques including HPLC and LC/MS. Elucidated structures based on the mass of the degrade using LCQ, LC/MS/MS.
Analytical Chemist, JR Laboratories Inc. - Vancouver, Canada 1997-2000
• Developed analytical methods for analysis of active components in drugs with HPLC, GC, TLC.
• Extraction, purification, identification and quantification of organic compounds from food and medicines.
• Government method validation more than 20 methods for drug residues in meat, egg and fruits for Agriculture Canada
Teaching Assistant, Department of Chemistry Simon Fraser University 1996-1997
• Teaching assistant in General Chemistry Laboratory.
Department of Chemistry, Harbin Medical University, Harbin, China 1986-1992
• Lecturer in Inorganic, Organic, Physical and Analytical Chemistry.
• Instructor, Inorganic, Organic and analytical labs.
• Research Assistant, Separation and identification of lipids in mouse brain by HPLC.
Bachelor of Science, Analytical Chemistry - Jilin University. China.
05/2010 Automation Hamilton Star platform training (Hamilton company)
06/2008 Drug Metabolism and Drug metabolizing Enzymes. CACO/BAADMEE Workshop
11/2007 Scientific basic Metabolite Analysis Utilizing a Q TRAP Mass by
07/2007 ACS Short Course: Kinetics of Enzyme Action -Basic Principles for Drug Hunters
06/2007 DMPK Training Series: Pharmacokinetics 101
08/2005 Watson LIMS 7.2 Training
08/2002 Quattro Ultima Basic Operator Training by Micromass
04/2002 Certificate, Analyst software, use and operation of the Sciex API 4000 Mass Spectrometer training (Applied Biosystems)
10/2001 Completed training program for LC/MS/MS 101 presented by Basic Mass Spec Solutions, Inc
• Special Recognition Awards ( for outstanding project support), 2011, ROCHE
PUBICATIONS AND POSTER PRESENTATION
Yuan Chen, Liling Liu, Khanh Nguyen, and Adrian J. Fretland. (2011) Utility of inter-system extrapolation factors (ISEFs) in early reaction phenotyping and the quantitative extrapolation of human liver microsomal intrinsic clearance using recombinant cytochrome P450s. Drug Metab Dispos 39:373-382;
Yuan Chen, Liling Liu, Mario Monshouwer and Adrian J. Fretland. (2011) Determination of Time-dependent Inactivation of CYP3A4 in Cryopreserved Human Hepatocyte and Assessment of Human Drug-Drug Interactions. Drug Metab Dispos 39:2085-2092
Yuan Chen, Hua-fen Liu, Liling Liu, Khanh Nguyen, Elliott B. Jones, and Adrian J. Fretland. (2010) the in vitro metabolism of bupropion revisited: concentration Dependent involvement of cytochrome P450 2C19. Xenobiotica, 1–11
Fitch, William L., Tran, Thuy, Young, May, Liu, Liling, Chen, Yuan. (2009) Revisiting the Metabolism of Ketoconazole Using Accurate Mass. Drug Metabolism Letters, Volume 3, Number 3, pp. 191-198
William L. Fitch, Yuan Chen, Liling Liu, Axel Paehler, May Young (2010) Application of Modern Drug Metabolism Structure Determination Tools and Assays to the In Vitro Metabolism of Imiloxan. Drug Metabolism Letter Apr2010, Vol. 4 Issue 2, p77.
Liling Liu, Karl B. Frank, Adrian J. Fretland, Barry Goggin, David Moore and Rob T. Taylor. Strategic use of EDTA-Free Subcellular Fractions for Better IVIVC in Early Drug Discovery. 2011 ISSX
Liling Liu, Rubén Alvarez Sanchez, Adrian Fretland, Barry Goggin, and Robert Taylor. Identification of responsible proteases involved in in vitro metabolism of Xiap chemical series. 2012 pRED Symposium.
Yuan Chen, Khanh Nugyen, Liling Liu, Adrian Fretland, Elliott Jones, Huafen Liu. Use of Q-Trap Mass Spectrometry in Cytochrome P450 (CYP450) Reaction Phenotyping of Bupropion. 2008 ASMS Conference
Hua-fen Liu, Elliott Jones, Khanh Nugyen, Liling Liu, Adrian Fretland, Yuan Chen. A Novel Analytical Method for Cytochrome 450 (CYP) Reaction Phenotyping Using Hybrid QTRAP. 2008 ISSX Asia Conference, 2008
Yuan Chen, Liling Liu, Adrian Fretland, William Fitch, Mario Monshouwer. Effects of GSH on CYP450 Enzyme Activity in In Vitro Assay. 2007 AAPS Conference, 2007
Tai, Ezra H.L., Liu, L., Frank, K., and Ludmila A. (2005) Evaluation of a phase II metabolite with irreversible CYP3A4 inhibition in human liver microsomes and hepatocyte cultures. Drug Metabolism Review 37 (suppl. 2) 258.
Tai, H.L. Ezra, Liu, Liling, Van Natta, K. Development of a high-throughput cytochrome P450 3A4 time-dependent inhibition assay. Poster 576 in 2004 ISSX Annual Meeting in Vancouver, Canada. Drug Metabolism Review 36 (suppl. 1) 288.