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  1. National Center for Toxicological Research

Li-Rong Yu Ph.D.

Li-Rong Yu

Team Leader — Division of Systems Biology

Dr. Li-Rong Yu
Li-Rong Yu, Ph.D.

(870) 543-7391
NCTRResearch@fda.hhs.gov  

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 About  |  Publications  |  Lab Members


Background

Dr. Li-Rong Yu studied biology at the Hangzhou Teachers College in China and graduated with a B.S. degree in 1991. He then attended the Institute of Hydrobiology, Chinese Academy of Sciences and earned an M.S. degree in hydrobiology in 1994. There he studied the origin, evolution, and phylogeny of the pseudogobiini fishes in East Asia. From 1994 to 1997, Dr. Yu worked as an engineer at the Institute of Reservoir Fisheries, Chinese Academy of Sciences, and studied the effects of nutrition and physiological factors on fish growth. He then attended the Shanghai Institute of Biochemistry, Chinese Academy of Sciences to study cancer proteomics and received a Ph.D. degree in biochemistry and molecular biology in 2000. In the same year, Dr. Yu came to the United States and conducted postdoctoral research in quantitative proteomics and biological mass spectrometry in Dr. Richard Smith’s group at the Pacific Northwest National Laboratory. From 2002 to 2007, Dr. Yu worked at the Laboratory of Proteomics and Analytical Technologies, SAIC-Frederick, Inc., National Cancer Institute in Frederick, Maryland. He worked as a scientist, senior scientist, and group head with studies focusing on the development of mass spectrometry-based quantitative proteomic technologies and their application to cancer biology. In 2007, Dr. Yu joined NCTR as a team leader and director for proteomics. His current research has focused on the development of proteomic biomarkers and understanding the mechanisms of drug-induced organ toxicity at the proteome level.

Research Interests
 

Predictive clinical biomarkers of chemotherapy-induced cardiotoxicity
Anthracycline-based chemotherapy is one of the major treatment tools for cancer patients, among which doxorubicin (Dox) is commonly used for the treatment of a wide range of cancers. However, a serious adverse side-effect is life-threatening cardiotoxicity (e.g., heart failure). Currently, imaging tests (e.g., echocardiography) are the most practical cardiotoxicity monitoring tools; however, they are costly and can only capture cardiotoxicity once functional impairment occurs. Blood biomarkers, such as cardiac troponin T (cTnT) and I (cTnI) are sensitive biomarkers of early cardiac-tissue damage, but their ability to predict cardiotoxicity is limited. Therefore, development of new predictive biomarkers to identify potential cardiotoxicity prior to the occurrence of overt cardiac-tissue damage would be extremely valuable for the prevention of permanent damage and/or identification of patients at highest risk for cardiac damage. To achieve this overall goal, breast-cancer patients are recruited and blood samples are collected before Dox treatment and at early time points after treatment. Blood samples are analyzed using systems biology approaches (i.e., SOMAscan-based proteomics, metabolomics, and miRNA analysis) to identify early biomarkers for the prediction of Dox-induced cardiotoxicity.

Proteomic biomarkers and mechanisms of drug-induced liver injury
Drug-induced liver injury (DILI) is one of the most frequent causes of drug-development failure and withdrawal of approved drugs. Overdose of APAP is well-known to cause clinical hepatotoxicity with a potential for acute liver failure. It is critical to detect potential liver injury at an early stage prior to onset of liver failure. By using a rat model treated with different doses of acetaminophen (APAP) — a model drug for hepatotoxicity — for different periods of time, we found molecular pathways evolved progressively from scattered and less significant perturbations to more focused and significant alterations in a dose- and time-dependent manner. Imbalanced expression of heme oxygenase 1 (HMOX1) and biliverdin reductase A (BLVRA) was associated with hepatotoxicity. Furthermore, abundance changes of 31 proteins were uniquely correlated to liver damage, and HMOX1 could be a potential plasma biomarker of liver injury as verified via cross-species and validated between plasma and liver tissues. The clinical diagnostic value of HMOX1 could be further explored.

Metabolomics and proteomics approaches addressing pre-analytical variability in human plasma samples
Research in the healthcare area for the identification and validation of new biomarkers, drug targets, and treatment monitoring approaches often starts with the analysis of existing biobank samples or clinical samples collected and processed by several, non-standardized, pre-analytical steps. The quality of these collected biobank and clinical samples can be impaired by altering pre-analytical processing steps that will confound the analytical results and decrease the value of research if not identified and addressed properly. Differences in sample processing will alter the composition of metabolites and proteins in blood samples and could affect diagnostic test results. To address these issues, blood samples were acquired from healthy volunteer subjects and processed to plasma under different conditions including blood and plasma storage time, temperature, and centrifugation force. Proteomics and metabolomics approaches are employed to discover biomarkers of sample quality related to variations in pre-analytical processing of clinical plasma samples. 


Professional Societies/National and International Groups

American Association for Cancer Research
Member
2004 – 2016

American Society for Mass Spectrometry
Member
2002 – Present

BioMed Research International
Guest Editor
2013

International Cardioncology Society
Member
2014 – Present 
 
Journal of Proteomics
Editorial Board Member
2009 – Present

Society of Toxicology
Poster Session Chair
2016

Member
2014 – Present

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Selected Publications

Early Metabolomics Changes in Heart and Plasma During Chronic Doxorubicin Treatment in B6C3F1 Mice.
Schnackenberg LK, Pence L, Vijay V, Moland CL, George N, Cao Z, Yu LR, Fuscoe JC, Beger RD, Desai VG.
J Appl Toxicol. 2016 Nov; 36(11):1486-95.

Proteomic Analysis of Acetaminophen-Induced Hepatotoxicity and Identification of Heme Oxygenase 1 as a Potential Plasma Biomarker of Liver Injury.
Gao Y, Cao Z, Yang X, Abdelmegeed MA, Sun J, Chen S, Beger RD, Davis K, Salminen WF, Song BJ, Mendrick DL, Yu LR.
Proteomics Clin Appl. 2016 Sep 16. doi: 10.1002/prca.201600123.

Early Transcriptional Changes in Cardiac Mitochondria During Chronic Doxorubicin Exposure and Mitigation by Dexrazoxane in Mice.
Vijay V, Moland CL, Han T, Fuscoe JC, Lee T, Herman EH, Jenkins GR, Lewis SM, Cummings CA, Gao Y, Cao Z, Yu LR, Desai VG.
Toxicol Appl Pharmacol. 2016 Mar 15; 295:68-84.

Critical Role of C-Jun N-Terminal Protein Kinase in Promoting Mitochondrial Dysfunction and Acute Liver Injury.
Jang S, Yu LR, Abdelmegeed MA, Gao Y, Banerjee A, Song BJ.
Redox Biol. 2015 Dec; 6:552-64.

Integrated MicroRNA, mRNA, and Protein Expression Profiling Reveals MicroRNA Regulatory Networks in Rat Kidney Treated with a Carcinogenic Dose of Aristolochic Acid.
Li Z, Qin T, Wang K, Hackenberg M, Yan J, Gao Y, Yu LR, Shi L, Su Z, Chen T.
BMC Genomics. 2015 May 8; 16:365.

Proteomics Quality and Standard: from a Regulatory Perspective.
Gu Q, Yu LR.
J Proteomics. 2014 Jan 16; 96:353-9.

Phosphopeptide Enrichment Using Offline Titanium Dioxide Columns for Phosphoproteomics.
Yu LR, Veenstra T.
Methods Mol Biol. 2013; 1002:93-103.

Functional Robustness of a Polycyclic Aromatic Hydrocarbon Metabolic Network Examined in a nidA Aromatic Ring-Hydroxylating Oxygenase Mutant of Mycobacterium Vanbaalenii PYR-1.
Kim SJ, Song J, Kweon O, Holland RD, Kim DW, Kim J, Yu LR, Cerniglia CE.
Appl Environ Microbiol. 2012 May; 78(10):3715-23.

Pharmacoproteomics and Toxicoproteomics: the Field of Dreams.
Yu LR.
J Proteomics. 2011 Nov 18; 74(12):2549-53. doi: 10.1016/j.jprot.2011.10.001. Epub 2011 Oct 8. Review.

Proteomic Analysis of Early Response Lymph Node Proteins in Mice Treated with Titanium Dioxide Nanoparticles.
Gao Y, Gopee NV, Howard PC, Yu LR.
J Proteomics. 2011 Nov 18; 74(12):2745-59.

Regulation of Microtubule-Based Microtubule Nucleation by Mammalian Polo-Like Kinase 1.
Johmura Y, Soung NK, Park JE, Yu LR, Zhou M, Bang JK, Kim BY, Veenstra TD, Erikson RL, Lee KS.
Proc Natl Acad Sci U S A. 2011 Jul 12; 108(28):11446-51.

Distinct Roles of GCN5/PCAF-Mediated H3K9ac and CBP/p300-Mediated H3K18/27ac in Nuclear Receptor Transactivation.
Jin Q, Yu LR, Wang L, Zhang Z, Kasper LH, Lee JE, Wang C, Brindle PK, Dent SY, Ge K.
EMBO J. 2011 Jan 19; 30(2):249-62.

Oxidant-Induced Apoptosis is Mediated by Oxidation of the Actin-Regulatory Protein Cofilin.
Klamt F, Zdanov S, Levine RL, Pariser A, Zhang Y, Zhang B, Yu LR, Veenstra TD, Shacter E.
Nat Cell Biol. 2009 Oct; 11(10):1241-6.

Quantitative Proteomics for Drug Toxicity.
Gao Y, Holland RD, Yu LR.
Brief Funct Genomic Proteomic. 2009 Mar; 8(2):158-66.

Improved Titanium Dioxide Enrichment of Phosphopeptides from HeLa Cells and High Confident Phosphopeptide Identification by Cross-Validation of MS/MS and MS/MS/MS Spectra.
Yu LR, Zhu Z, Chan KC, Issaq HJ, Dimitrov DS, Veenstra TD.
J Proteome Res. 2007 Nov; 6(11):4150-62.

Phosphoproteomics for the Discovery of Kinases as Cancer Biomarkers and Drug Targets.
Yu LR, Issaq HJ, Veenstra TD.
Proteomics Clin Appl. 2007 Sep; 1(9):1042-57.

Self-Regulated Plk1 Recruitment to Kinetochores by the Plk1-PBIP1 Interaction is Critical for Proper Chromosome Segregation.
Kang YH, Park JE, Yu LR, Soung NK, Yun SM, Bang JK, Seong YS, Yu H, Garfield S, Veenstra TD, Lee KS.
Mol Cell. 2006 Nov 3; 24(3):409-22.

Regulation of Androgen Receptor Activity by Tyrosine Phosphorylation.
Guo Z, Dai B, Jiang T, Xu K, Xie Y, Kim O, Nesheiwat I, Kong X, Melamed J, Handratta VD, Njar VC, Brodie AM, Yu LR, Veenstra TD, Chen H, Qiu Y.
Cancer Cell. 2006 Oct; 10(4):309-19.

Global Analysis of the Cortical Neuron Proteome.
Yu LR, Conrads TP, Uo T, Kinoshita Y, Morrison RS, Lucas DA, Chan KC, Blonder J, Issaq HJ, Veenstra TD.
Mol Cell Proteomics. 2004 Sep; 3(9):896-907.

Evaluation of the Acid-Cleavable Isotope-Coded Affinity Tag Reagents: Application to Camptothecin-Treated Cortical Neurons.
Yu LR, Conrads TP, Uo T, Issaq HJ, Morrison RS, Veenstra TD.
J Proteome Res. 2004 May-Jun; 3(3):469-77.

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Lab Members

Contact information for all lab members:
(870) 543-7391
NCTRResearch@fda.hhs.gov   

 

Zhijun Cao, Ph.D.
Staff Fellow

Jaclyn D. Daniels, Ph.D.
ORISE Postdoctoral Fellow

Elizabeth (Ellen) Jones, Ph.D.
Staff Fellow
 

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Contact Information
Li-Rong Yu
(870) 543-7391
Expertise
Approach