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U.S. National Institutes of Health
Cancer Diagnosis Program Cancer Imaging Program Cancer Therapy Evaluation Program Developmental Therapeutics Program Radiation Research Program Translational Research Program Biometric Research Branch Office of Cancer Complementary and Alternative Medicine
Last Updated: 04/25/2012

SCIENTIFIC ADVANCES

Contributed by Dr. Yingdong Zhao

Dr. Yingdong Zhao conducts research on the development of statistical methods and bioinformatics approaches for using high-throughput data to identify cancer-specific markers that increase the sensitivity and accuracy of cancer diagnosis and treatment. His research also focuses on the development of statistical methods and immunoinformatic approaches for using genomic data and immunologic assays to elucidate the molecular events in T-cell immune response to pathogens in autoimmune processes and to identify molecular targets for therapeutic vaccines.

Dr. Zhao has participated in several collaborations with other NCI and NIH scientists and with national and international research groups. These research projects have been highly productive, resulting in 18 peer-reviewed papers in the past 2 years. The papers cover a range of topics, including the use of microRNA expression to distinguish histology and predict survival of patients with lung cancer, the development of gene expression profiles as predictive biomarkers for better understanding the determinants of response to immunotherapy in patients with metastatic melanoma, the combination of positional scanning peptide libraries, HLA-DR transfectants and bioinformatics to dissect the epitope spectrum of HLA-class II cross-restricted CD4+ T-cell clones, and computational methods for studying partial immunity and vaccination for influenza.

Dr. Zhao has continued to be actively involved in the development and support of BRB-ArrayTools, a software for microarray gene expression analysis. He has worked with Dr. Simon and developed a plug-in for BRB-ArrayTools including international dissemination of software for Least Angle Regression (LARS), which can be used to develop predictive indices for a continuous outcome using gene expression profiles. He has also involved in a project with Mr. Qi, Drs. Simon and Li in the development of a BRB-ArrayTools plug-in for non-negative matrix factorization of gene expression profiles. Drs. Zhao and Simon have continued to develop and enhance a data archive of publicly available gene expression datasets and corresponding clinical data for published human cancer gene expression profiling studies, which has been widely used in the research community, with more than 700 hits per month.

Dr. Zhao together with Dr. Simon and other BRB colleagues have continued to develop, enhance, and maintain programs on the BRB website for the design of clinical trials involving new drugs and predictive biomarkers. Dr. Zhao has collaborated with Drs. Hunsberger and Simon and developed a web-based planning tool for the design of integrated phase 2/3 designs. Together with Drs. Dobbin and Simon, Dr. Zhao developed web-based sample size planning software for developing classifiers using high-dimensional data. All of these web-based programs have been widely used and have hundreds of hits each month.

Zhao Y, Simon R. Development and validation of predictive indices for a continuous outcome using gene expression profiles. Cancer Inform 2010:9;105-114. http://www.ncbi.nlm.nih.gov/pubmed/20523915

Zhao Y, Simon R. Gene expression deconvolution in clinical samples. Genome Med 2010: 2;93. http://genomemedicine.com/content/2/12/93

Zhao Y, Wang E, Liu H, Rotunno M, Koshiol J, Landi MT, McShane LM. Evaluation of normalization methods for two-channel microRNA microarray. J Transl Med 2010:8;69. http://www.ncbi.nlm.nih.gov/pubmed/20663154

Zhao Y, Simon R. T cell epitope, prediction with peptide libraries. In: Encyclopedia of System Biology. Dubitzky W, Wolkenhauer O, Cho K-H, Yokota H, eds. New York:Springer; 2011.

Sospedra M, Zhao Y, Giulianotti M, Simon R, Pinilla C, Martin R. Combining Positional Scanning Peptide Libraries, HLA-DR Transfectants and Bioinformatics to Dissect the Epitope Spectrum of HLA-class II Cross-Restricted CD4+ T Cell Clones. J Immunol Methods 2010:353;93-101. doi:10.1016/j.jim.2009.12.006

Landi MT, Zhao Y, Rotunno M, Koshiol J, Liu H, Bergen AW, Rubagotti M, Goldstein AM, Linnoila I, Marincola FM, Tucker MA, Bertazzi PA, Pesatori AC, Caporaso NE, McShane LM, Wang E. MicroRNA expression differentiates histology and predicts survival of lung cancer. Clin Cancer Res 2010:16;430-41. http://www.ncbi.nlm.nih.gov/pubmed/20068076

Zhang X, Zhao Y, Neumann A. Partial immunity and vaccination for influenza. J Comput Biol 2010:17;1689-96. http://www.ncbi.nlm.nih.gov/pubmed/21128855

Rotunno M, Zhao Y, Bergen AW, Koshiol J, Burdette L, Rubagotti M, Linnoila RI, Marincola FM, Bertazzi PA, Pesatori AC, Caporaso NE, McShane LM, Wang E, Landi MT. Inherited polymorphisms in the RNA-mediated interference machinery affect microRNA expression and lung cancer survival. Br J Cancer 2010:103;1870-4. http://www.ncbi.nlm.nih.gov/pubmed/21102586

Koshiol J, Wang E, Zhao Y, Landi MT. Strengths and limitations of laboratory procedures for microRNA detection. Cancer Epidemio, Biomarkers Prev 2010:19;907-11. http://www.ncbi.nlm.nih.gov/pubmed/20332265

Woelk CH, Beliakova-Bethell N, Goicoechea M, Zhao Y, Du P, Rought SE, Lozach J, Pérez-Santiago J, Richman DD, Smith DM, Little SJ. Gene expression before HAART initiation predicts HIV-infected individuals at risk of poor CD4+ T cell recovery. AIDS 2010:24;217-222. http://www.ncbi.nlm.nih.gov/pubmed/19952713

Zhao Y, Simon R. Deconvolution of positional scanning synthetic combinatorial libraries: Mathematical models and bioinformatics approaches. In: Computational Biology:New Research. Russe AS, ed. New York:Nova Science Publishers; 2009.

Hunsberger S, Zhao Y, Simon R. A comparison of Phase II study strategies. Clin Cancer Res 2009:15;5950–55. http://www.ncbi.nlm.nih.gov/pubmed/19789306

Qi Q, Zhao Y, Li MC, Simon R. Nonnegative matrix factorization of gene expression profiles: a plug-in for BRB-ArrayTools. Bioinformatics 2009:25;545-47. http://www.ncbi.nlm.nih.gov/pubmed/19131367

Tahara H, et al., Zhao Y, Zocca MB, Marincola, FM. Emerging concepts in biomarker discovery. J Transl Med 2009:7;45.

Respa A, Bukur J, Ferrones, Pawelec G, Zhao Y, Wang E, Marincola, FM, Seliger B. Association of IFN-gamma signal transduction defects with impaired HLA class I antigen processing in melanoma cell lines. Clin Cancer Res (In press).

Ascierto ML, Kmieciak M, Idowu MO, Manjili R, Zhao Y, Grimes M, Dumur C, Wang E, Ramakrishnan V, Wang XY, Bear HD, Marincola FM, Manjili MH. A signature of immune function genes associated with recurrence-free survival in breast cancer patients. Breast Cancer Research (In press).

Koshiol J, Gulley ML, Zhao Y, Rubagotti M, Marincola FM, Rotunno M, Tang W, Bergen AW, Bertazzi PA, Roy D, Pesatori AC, Linnoila I, Dittmer D, Goldstein AM, Caporaso NE, McShane LM, Wang E, Landi MT. Epstein-Barr virus (EBV) miRs but no EBV in lung cancer: smoke without fire? (Submitted).

Yen W, Erickson H. Zhao Y, Simon R et al. Characterization of targeted-therapy related molecular biomarkers from NSCLC ever-smokers versus never-smokers by a novel qRT-PCR for microdissected tissues methodology. (In preparation).

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