Siyuan Zheng, PhD

 

Our lab is located at the Greehey Cancer Research Institute (GCCRI). We use genomic and proteomic data to understand the mechanisms behind the initiation, progression, treatment responses of pediatric and adult cancers. Our research is focused to identifying aberrations in cancer, including single nucleotide variations, insertions, deletions, DNA and RNA structural rearrangements, DNA copy number alterations, that facilitate the various aspect of the cancer ecosystem.

We welcome motivated researchers and students with similar interest to join our team! We welcome motivated researchers and students with similar interest to join our team!

Latest Research

In this analysis we calculated telomere lengths for more than 10,000 human cancers from TCGA. We examined possible genetic and epigenetic mechanisms underlying telomerase reactivation and alternative lengthening of telomeres. Barthel et al. Nat Genet. 2017 Mar;49(3):349-357

We as a TCGA analysis working group comprehensively characterized the genomic and clinical profiles of 91 adrenocortical carcinomas, a rare but deadly endocrine cancer originating in the adrenal gland. Zheng et al. Cancer Cell. 2016 May 9;29(5):723-36.

 

 

 

Hu X, Wang Q, Tang M, Barthel FP, Amin S, Yoshihara K, Lang FM, Martinez-Ledesma E, Lee SH, Zheng S*, Verhaak RG*. TumorFusions: an integrative resource for cancer-associated transcript fusions. Nucleic Acids Research. In press. Co-correspondence.

Zheng S. Benchmarking: contexts and details matter. Genome Biology. 2017 Jul 5;18(1):129. doi: 10.1186/s13059-017-1258-3. Editorial.

Farshidfar F, Zheng S, Gingras MC, Newton Y, Shih J, Robertson A.G, Hinoue T, Hoadley KA, …, Roberts LR, Kwong LN on behalf of TCGA. Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH-Mutant Molecular Profiles. Cell Reports. 2017 Mar 14;18(11):2780-2794. doi: 10.1016/j.celrep.2017.02.033.

Barthel FP, Wei W, Tang M, Martinez-Ledesma E, Hu X, Amin S, Akdemir K, Seth S, Song X, Wang Q, Lichtenberg T, Hu J, Zhang J, Zheng S*, Verhaak RG*. Systematic Analysis of Telomere Length and Somatic Alterations in 31 Cancer Types. Nat Genet. 2017 Jan 30. doi: 10.1038/ng.3781.. Co-correspondence.

• Science Daily: Unraveling the mystery of why cancer cells survive and thrive

Zheng S, Cherniack AD, Dewal N, Moffitt RA, Danilova L, Murray BA, Lerario AM, Else T, Knijnenburg TA, Ciriello G, Kim S, Assie G, Morozova O, Akbani R, Shih J, Hoadley KA, Choueiri TK, Waldmann J, Mete O, Robertson AG, Raphael BJ, Meyerson M, Demeure MJ, Beuschlein F, Gill AJ, Sidhu SB, Almeida MQ, Fragoso MC, Cope LM, Kebebew E, Habra MA, Whitsett TG, Bussey KJ, Rainey WE, Asa SL, Bertherat J, Fassnacht M, Wheeler DA, The Cancer Genome Atlas Research Network, Hammer GD, Giordano TJ, Verhaak RG. Comprehensive Pan-Genomic Characterization of Adrenocortical Carcinoma. Cancer Cell, 2016; 29 (5): 723 DOI: 10.1016/j.ccell.2016.04.002

• Science Daily: Study shows possible 'key' to improved therapy for adrenocortical carcinoma

• Nature Reviews Endocrinology: The genetics of adrenocortical carcinoma revealed

The Cancer Genome Atlas Research Network. Comprehensive, Integrative Genomic Analysis of Diffuse Lower Grade Gliomas. New England Journal of Medicine. June 10, 2015 | DOI: 10.1056/NEJMoa1402121. Zheng S contributing to gene fusion/expression subtype analyses.

Kim H*, Zheng S*, Amini S, Virk SM, Mikkelsen T, Brat DJ,Jonna Grimsby, Carrie Sougnez, Florian Muller, Jian Hu, Andrew E. Sloan, Mark L. Cohen, Erwin G. Van Meir, Lisa Scarpace, Peter W. Laird, John N. Weinstein, Eric Lander, Stacey Gabriel, Gad Getz, Matthew Meyerson, Lynda Chin, Barnholtz-Sloan JS, Verhaak RG. Whole genome and multi-sector sequencing of primary and post-treatment glioblastoma illustrates patterns of tumor evolution. Genome Res. 2015 Mar;25(3):316-27. doi: 10.1101/gr.180612.114. Epub 2015 Feb 3. Equal contribution.

• “Breaking Advances”, Cancer Res, 2015;75:1159-1160.

• “Highlights from the literature”, Neuro-Oncology, 2015;17(6):773-775.

Torres-García W*, Zheng S*, Sivachenko A*, Vegesna R, Wang Q, Yao R, Berger MF, Weinstein JN, Getz G, Verhaak RG. PRADA: Pipeline for RNA Sequencing Data Analysis. Bioinformatics. 2014 Apr 1. Equal contribution.

Zheng S, Kim H, Verhaak RG. Silent mutations make some noise. Cell. 2014 Mar 13;156(6):1129-31. doi: 10.1016/j.cell.2014.02.037. Editorial.

Guan X*, Vengoechea J*, Zheng S*, Sloan AE, Chen Y, Brat DJ, O'Neill BP, de Groot J, Yust-Katz S, Yung WK, Cohen ML, Aldape KD, Rosenfeld S, Verhaak RG, Barnholtz-Sloan JS.Association between glioblastoma molecular subtypes and lower grade gliomas. PLoS One. 2014 Mar 10;9(3):e91216. doi: 10.1371/journal.pone.0091216. Equal contribution.

Chudnovsky Y, Kim D, Zheng S, Whyte WA, Bansal M, Bray MA, Gopal S, Theisen MA, Bilodeau S, Thiru P, Muffat J, Yilmaz OH, Mitalipova M, Woolard K, Lee J, Nishimura R, Sakata N, Fine HA, Carpenter AE, Silver SJ, Verhaak RG, Califano A, Young RA, Ligon KL, Mellinghoff IK, Root DE, Sabatini DM, Hahn WC, Chheda MG. ZFHX4 interacts with the NuRD complex and regulates the glioblastoma tumor initiating cell state. Cell Reports. 2014 Jan 15. pii: S2211-1247(13)00790-0.

Brennan CW, Verhaak RG, McKenna A, Campos B, Noushmehr H, Salama SR, Zheng S, Chakravarty D, Sanborn JZ, Berman SH, Beroukhim R, Bernard B, Wu CJ, Genovese G, Shmulevich I, Barnholtz-Sloan J, Zou L, Vegesna R, Shukla SA, Ciriello G, Yung WK, Zhang W, Sougnez C, Mikkelsen T, Aldape K, Bigner DD, Van Meir EG, Prados M, Sloan A, Black KL, Eschbacher J, Finocchiaro G, Friedman W, Andrews DW, Guha A, Iacocca M, O'Neill BP, Foltz G, Myers J, Weisenberger DJ, Penny R, Kucherlapati R, Perou CM, Hayes DN, Gibbs R, Marra M, Mills GB, Lander E, Spellman P, Wilson R, Sander C, Weinstein J, Meyerson M, Gabriel S, Laird PW, Haussler D, Getz G, Chin L; TCGA Research Network. The somatic genomic landscape of glioblastoma. Cell. 2013 Oct 10; 155(2):462-477.

Saito N, Fu J, Zheng S, Yao J, Wang S, Liu DD, Yuan Y, Sulman EP, Lang FF, Colman H, Verhaak RG, Yung WK, Koul D. A high Notch pathway activation predicts response to γ-secretase inhibitors in proneural subtype of glioma tumor initiating cells. Stem Cells. 2013 Aug 27. doi: 10.1002/stem.1528.

Zheng S, Verhaak RG. Intragenic breakpoint: a marker of genome instability in glioblastoma. Cell Cycle. 2013 Oct 21;12(24). Editorial

Zheng S, Fu J, Vegesna R, Mao Y, Heathcock LE, Torres-Garcia W, Ezhilarasan R, Wang S, McKenna A, Chin L, Brennan CW, Yung WK, Weinstein JN, Aldape KD, Sulman EP, Chen K, Koul D, Verhaak RG. A survey of intragenic breakpoints in GBM identifies a distinct subset associated with poor survival. Genes Dev. 2013 Jul 1;27(13):1462-72.

• Commentary, Zheng et al. Cell Cycle. 2013 Oct 21;12(24).

Zheng S, Chheda MG, Verhaak RG. Studying a Complex Tumor—Potential and Pitfalls. Cancer J. 2012 Jan-Feb;18(1):107-14. Review.

Zheng S, Zhao Z. DNA methylation profiling distinguishes three clusters of breast cancer cell lines. Chem Biodivers. 2012 May;9(5):848-56. doi: 10.1002/cbdv.201100354.

Zheng S, Zhao Z. GenRev: exploring gene relevance in molecular networks. Genomics. 2012 Mar;99(3):183-8. doi: 10.1016/j.ygeno.2011.12.005. Epub 2011 Dec 29. Software is available at http://bioinfo.mc.vanderbilt.edu/GenRev.html

Zheng S, Tansey WP, Hiebert SW, Zhao Z. Integrative network analysis identifies key genes and pathways in the progression of Hepatitis C virus induced hepatocellular carcinoma. BMC Med Genomics. 2011 Aug 8;4(1):62.

Sun Y*, Zheng S*, Torossian A, Speirs CK, Schleicher S, Giacalone NJ, Carbone DP, Zhao Z, Lu B. Genetic profiling of lung cancer stem-like cells reveals IGF-1 signaling pathway as a promising target to improve treatment response. International Journal of Radiation Oncology, Biology, Physics. 2011 Dec 22. Equal contribution.

Jia P*, Zheng S*, Long J, Zheng W, Zhao Z. dmGWAS: dense module searching for genome-wide association studies in protein-protein interaction networks. Bioinformatics. (2010) doi: 10.1093/bioinformatics/btq615. Equal contribution. F1000Prime Recommendation (http://m.f1000.com/prime/6469956)

Yu Y*, Tu K*, Zheng S, Li Y, Ding G, Ping J, Hao P, Li Y. GEOGLE: Context Mining Tool for the Correlation between Gene Expression and the Phenotypic Distinction. BMC Bioinformatics. 2009 Aug 25;10:264

Hao P*, Zheng S*, Ping J, Tu K, Gieger C, Wang-Sattler R, Zhong Y, Li Y. Human gene expression sensitivity according to large scale meta-analysis. BMC Bioinformatics. 2009 Jan 30;10 Suppl 1:S56. Equal contribution.

Zheng S, Sheng J, Wang C, Wang X, Yu Y, Li Y, Michie A, Dai J, Zhong Y, Hao P, Liu L, Li Y. MPSQ: a web tool for protein-state searching.Bioinformatics. 2008 Oct 15;24(20):2412-3.

 

Other papers

Wu S, Wang S, Gao F, Li L, Zheng S, Yung WKA, Koul D. Activation of WEE1 confers resistance to PI3K inhibition in glioblastoma. Neuro Oncol. 2017 Jul 7. doi: 10.1093/neuonc/nox128.

 

Wang Q, Hu B, Hu X, Kim H, Squatrito M, Scarpace L, deCarvalho AC, Lyu S, Li P, Li Y, Barthel F, Cho HJ, Lin YH, Satani N, Martinez-Ledesma E, Zheng S, Chang E, Sauvé CG, Olar A, Lan ZD, Finocchiaro G, Phillips JJ, Berger MS, Gabrusiewicz KR, Wang G, Eskilsson E, Hu J, Mikkelsen T, DePinho RA, Muller F, Heimberger AB, Sulman EP, Nam DH, Verhaak RGW. Tumor Evolution of Glioma-Intrinsic Gene Expression Subtypes Associates with Immunological Changes in the Microenvironment. Cancer Cell. 2017 Jul 10;32(1):42-56.e6. doi: 10.1016/j.ccell.2017.06.003.

The Cancer Genome Atlas Research Network. Comprehensive and Integrative Genomic Characterization of Hepatocellular Carcinoma. Cell. 2017 Jun 15;169(7):1327-1341.e23. doi: 10.1016/j.cell.2017.05.046. Zheng S contributed to gene fusion analysis.

Lee SH, Kim JS, Zheng S, Huse JT, Bae JS, Lee JW, Yoo KH, Koo HH, Kyung S, Park WY, Sung KW. ARID1B alterations identify aggressive tumors in neuroblastoma. Oncotarget. 2017 Apr 28. doi: 10.18632/oncotarget.17500.

Wang Y, Wu S, Zheng S, Wang S, Wali A, Ezhilarasan R, Sulman EP, Koul D, Yung W.K.A. APOBEC3G acts as a therapeutic target in mesenchymal gliomas by sensitizing cells to radiation-induced cell death. Oncotarget. 2017 Apr 21. doi: 10.18632/oncotarget.17348.

Koul D, Wang S, Wu S, Saito N, Zheng S, Gao F, Kaul I, Setoguchi M, Nakayama K, Koyama K, Shiose Y, Sulman EP, Hirota Y, Yung W.K. A. Preclinical therapeutic efficacy of a novel blood-brain barrier-penetrant dual PI3K/mTOR inhibitor with preferential response in PI3K/PTEN mutant glioma. Oncotarget. 2017 Mar 28;8(13):21741-21753. doi: 10.18632/oncotarget.15566.

Hu X, Martinez-Ledesma E, Zheng S, Kim H, Barthel F, Jiang T, Hess KR, Verhaak RG. Multigene signature for predicting prognosis of patients with 1p19q co-deletion diffuse glioma. Neuro Oncol. 2017 Mar 8. doi: 10.1093/neuonc/now285.

Shingu T, Ho AL, Yuan L, Zhou X, Dai C, Zheng S, Wang Q, Zhong Y, Chang Q, Horner JW, Liebelt BD, Yao Y, Hu B, Chen Y, Fuller GN, Verhaak RG, Heimberger AB, Hu J. Qki deficiency maintains stemness of glioma stem cells in suboptimal environment by downregulating endolysosomal degradation. Nat Genet. 2016 Nov 14. doi: 10.1038/ng.3711.

Wu S, Wang S, Zheng S, Verhaak R, Koul D, Yung WK. MSK1-Mediated ß-Catenin Phosphorylation Confers Resistance to PI3K/mTOR Inhibitors in Glioblastoma. Mol Cancer Ther. 2016 Jul;15(7):1656-68. doi: 10.1158/1535-7163.MCT-15-0857.

Ceccarelli M, Barthel FP, Malta TM, Sabedot TS, Salama SR, Murray BA, Morozova O, Newton Y, Radenbaugh A, Pagnotta SM, Anjum S, Wang J, Manyam G, Zoppoli P, Ling S, Rao AA, Grifford M, Cherniack AD, Zhang H, Poisson L, Carlotti CG Jr, Tirapelli DP, Rao A, Mikkelsen T, Lau CC, Yung WK, Rabadan R, Huse J, Brat DJ, Lehman NL, Barnholtz-Sloan JS, Zheng S, Hess K, Rao G, Meyerson M, Beroukhim R, Cooper L, Akbani R, Wrensch M, Haussler D, Aldape KD, Laird PW, Gutmann DH; TCGA Research Network, Noushmehr H, Iavarone A, Verhaak RG. Molecular Profiling Reveals Biologically Discrete Subsets and Pathways of Progression in Diffuse Glioma. Cell. 2016 Jan 28;164(3):550-63. doi: 10.1016/j.cell.2015.12.028.

Phan LM, Fuentes-Mattei E, Wu W, Velazquez-Torres G, Sircar K, Wood CG, Hai T, Jimenez C, Cote GJ, Ozsari L, Hofmann MC, Zheng S, Verhaak R, Pagliaro L, Cortez MA, Lee MH, Yeung SC, Habra MA. Hepatocyte Growth Factor/cMET Pathway Activation Enhances Cancer Hallmarks in Adrenocortical Carcinoma. Cancer Res. 2015 Oct 1;75(19):4131-42.

Geisenberger C, Mock A, Warta R, Rapp C, Schwager C, Nied A-K, Capper D, Brors B, Jungk C, Jones D, Collins V.P., Korshunov A, Ichimura K, Backlund L.M., Schnabel E, Mittelbron M, Lahrmann B, Zheng S, Verhaak R.G., Grabe N, Pfister S.M., Hartmann C, Deimling A, Debus J, Unterberg A, Abdollahi A, Herold-Mende C. Molecular profiling of long- and short-term survivors reveals concurrent gains of chromosome 19 and 20 as a prognostic factor in non-G-CIMP glioblastoma. Acta Neuropathologica. 2015 Sep;130(3):419-34. doi: 10.1007/s00401-015-1427-y.

Han L, Guo Y, Su Z, Zheng S, Lu Z. Advances in computational genomics. Biomed Res Int. 2015;2015:187803. doi: 10.1155/2015/187803. Epub 2015 Jan 6. Editorial.

Yoshihara K, Wang Q, Torres-Garcia W, Zheng S, Vegesna R, Kim H, Verhaak RG. The landscape and therapeutic relevance of cancer-associated transcript fusions. Oncogene. 2014 Dec 15. doi: 10.1038/onc.2014.406.

The Cancer Genome Research Network. Multiplatform analysis of 12 cancer types reveals molecular classification within and across tissues of origin. Cell. 2014 Aug 14;158(4):929-44. doi: 10.1016/j.cell.2014.06.049. Epub 2014 Aug 7. Zheng S is a collaborator.

Han L, Yuan Y, Zheng S, Yang Y, Li J, Edgerton ME, Diao L, Xu Y, Verhaak RG, Liang H. The Pan-Cancer analysis of pseudogene expression reveals biologically and clinically relevant tumour subtypes. Nat Commun. 2014 Jul 7;5:3963. doi: 10.1038/ncomms4963.

Cancer Genome Atlas Pan-Cancer analysis project. Nat Genet. 2013 Sep 26;45(10):1113-20. doi: 10.1038/ng.2764. Zheng S is a collaborator.

Hill MF, Patel AV, Murphy A, Smith HM, Pentassuglia L, Peng X, Galinda CL, Odiete O, Friedman DB, Kronenberg M, Zheng S, Zhao Z, Song Y, Harrell FE, Srinivas M, Ganguly A, Laci J,Parry T, Caggiano AO, Sawyer DB. Intravenous Glial Growth Factor 2 (GGF2) Isoform of Neuregulin-1 beta Improves Left Ventricular Function, Gene and Protein Expression in Rats after Myocardial Infarction. PLOS ONE. 2013;8(2):e55741. doi: 10.1371/journal.pone.0055741. Epub 2013 Feb 21.

Flynn C, Zheng S, Yan L, Hedges L, Womack B, Fessel J, Cogan J, Austin E, Loyd J, West J, Zhao Z, Hamid R. Connectivity Map Analysis of NMD+ BMPR2 Related HPAH Provides Insights into Disease Penetrance. Am J Respir Cell Mol Biol. 2012 Feb 3.

Simpson DR, Yu M, Zheng S, Zhao Z, Muthuswamy SK, Tansey WP. Epithelial cell organization suppresses Myc function by attenuating Myc expression. Cancer Res. 2011 Jun 1;71(11):3822-30. doi: 10.1158/0008-5472.CAN-10-3782. Epub 2011 May 24.

Huang, HC, Zheng S, VanBuren V, Zhao Z. Discovering Disease-specific Biomarker Genes for Cancer Diagnosis and Prognosis. Technologies in Cancer Research and Treatment. 2010 Jun;9(3):219-30.

Han L, Zheng S, Sun S, Huang T, Zhao Z. Genome wide methylation profiling in 40 breast cancer cell lines. Lecture notes in computer sciences. 2010, 6215:277-284.

Bhaskara S, Knutson SK, Jiang G, Chandrasekharan MB, Wilson AJ, Zheng S, Yenamandra A, Locke K, Yuan JL, Bonine-Summers AR, Wells CE, Kaiser JF, Washington MK, Zhao Z, Wagner FF, Sun ZW, Xia F, Holson EB, Khabele D, Hiebert SW. Hdac3 is essential for the maintenance of chromatin structure and genome stability. Cancer Cell. 2010 Nov 16;18(5):436-47.

 

Liu X, Ouyang S, Yu B, Liu Y, Huang K, Gong J, Zheng S, Li Z, Li H, Jiang H. PharmMapper server: a web server for potential drug target identification using pharmacophore mapping approach. Nucleic Acids Res. 2010 Jul;38(Web Server issue):W609-14. Epub 2010 Apr 29. PMCID: 20430828

Li Y, Hao P, Zheng S, Tu K, Fan H, Zhu R, Ding G, Dong C, Wang C, Li X, Thiesen HJ, Chen YE, Jiang H, Liu L, Li Y. Gene expression module-based chemical function similarity search. Nucleic Acids Res. 2008 Nov;36(20):e137.

Wang X, Wu D, Zheng S, Sun J, Tao L, Li Y, Cao Z. Ab-origin: an enhanced tool to identify the sourcing gene segments in germline for rearranged antibodies. BMC Bioinformatics. 2008 Dec 12;9 Suppl 12:S20.

Yang J, Cui B, Sun S, Shi T, Zheng S, Bi Y, Liu J, Zhao Y, Chen J, Ning G, Li X. Phenotype-genotype correlation in eight Chinese 17alpha-hydroxylase/17,20 lyase-deficiency patients with five novel mutations of CYP17A1 gene. J Clin Endocrinol Metab. 2006 Sep;91(9):3619-25.