Jinghui Zhang, PhD
Jinghui Zhang, PhD

Jinghui Zhang, PhD

Member, St. Jude Faculty

  • Chair, Department of Computational Biology
  • St. Jude Endowed Chair in Bioinformatics

Departments

Education

BS – Fu Dan University, Shanghai, China (1989)
MS – The University of Connecticut, Storrs, Connecticut (1991)
PhD – The University of Connecticut, Storrs, Connecticut (1994)

Research Interests

I am a computational biologist focused on the integrative analysis of large-scale, multi-dimensional genomic data to understand the initiation and progression of diseases. My research interest has been in the development of highly accurate and sensitive computational methods for analyzing large-scale genomic data, especially in the area of detecting and analyzing genetic variations and somatic mutations. Early in my career, I participated in the development of the widely used BLAST algorithm and led the genetic variation analysis of the first assembled human genome. Development of visualization tools for viewing integrative genomic data is another key interest as these tools are indispensable for gaining understanding of the experimental data and for reviewing the accuracy of the computational results obtained from the astronomical volume of the genomic data generated with the current technology. My group has developed computational tools for analyzing genetic variations and somatic mutations, which have contributed to the key discoveries made in the pilot phase of two major cancer genomic initiatives of the National Cancer Institute: Cancer Genome Atlas Project (TCGA) and the Therapeutically Applicable Research to Generate Effective Treatment (TARGET). 

Understanding the genetic origin of pediatric cancers is currently the main focus of my research as my group is primarily responsible for analyzing the next-generation sequencing data generated from the St. Jude Children’s Research Hospital - Washington University Pediatric Cancer Genome Project (PCGP). Developing novel approaches and data management infrastructure that integrate whole-genome sequencing data with RNA sequencing, copy number, gene expression, and proteomics data is an ongoing effort. Most recently we developed a suite of algorithms, CREST, CONSERTING and CICERO, for discovery of structural variations and copy number alterations in cancer genome at high accuracy. We discovered recurrently mutated biological pathways and genes in pediatric acute lymphoblastic leukaemia, retinoblastoma, high-grade glioblastoma, low-grade glioma, neuroblastoma, medulloblastoma, and ependymoma by whole-genome, whole-exome and transcriptome sequencing. I have developed mathematical models for mapping clonal evolution trajectory from diagnosis to relapse for pediatric solid tumor and leukemia. I have played leading role in major studies that have examined the nature of inherited genetic variants in both human and mouse genomes including describing single nucleotide variants in one of the first sequenced human genomes and prevalence of germline mutations causing cancer susceptibility in >1000 children with cancer.

Selected Publications

See also Zhang publications at stjuderesearch.org.

Zhang J, Walsh MF, Wu G, Edmonson MN, Gruber TA, Easton J, Hedges D, Ma X, Zhou X, Yergeau DA, Wilkinson MR, Vadodaria B, Chen X, McGee RB, Hines-Dowell S, Nuccio R, Quinn E, Shurtleff SA, Rusch M, Patel A, Becksfort JB, Wang S, Weaver MS, Ding L, Mardis ER, Wilson RK, Gajjar A, Ellison DW, Pappo AS, Pui C-H, Nichols KE, Downing JR. Germline Mutations in Predisposition Genes in Pediatric Cancer. N Engl J Med Dec 10;373(24):2336-46, 2015. doi: 10.1056/NEJMoa1508054. Epub 2015 Nov 18. PMID: 26580448. PMCID: PMC4734119.

Zhou X, Edmonson MN, Wilkinson MR, Patel A, Wu G, Liu Y, Li Y, Zhang Z, Rusch MC, Parker M, Becksfort J, Downing JR, Zhang J. Exploring genomic alteration in pediatric cancer using ProteinPaint. Nat Genet Dec 29;48(1):4-6, 2015. doi: 10.1038/ng.3466. PubMed PMID: 26711108.

Chen X, Gupta P, Wang J, Nakitandwe J, Roberts K, Dalton JD, Parker M, Patel S, Holmfeldt L,  Payne D, Easton J, Ma J, Rusch M, Wu G, Patel A, Baker S, Dyer M, Shurtleff S, Espy S, Pounds S, Downing J, Ellison D, Mullighan C, and Zhang J. CONSERTING: an accurate method for detecting somatic DNA copy number alterations in whole genome sequencing data. Nature Meth 12(6):527-30, 2015. PMID: 25938371. PMCID: PMC4591043.

Ma X, Edmonson M, Yergeau D, Muzny DM, Hampton, OA, Rusch M,  Song G, Easton J, Harvey RC, Wheeler DA, Ma J, Doddapaneni HV, Vadodaria B,  Wu G, Nagahawatte P, Carroll WL, Chen, I-M Chen, Gastier-Foster JM, Relling MV, Smith MA, Devidas M, Guidry Auvil JM, Downing JR, Loh ML, Willman CL, Gerhard DS, Mullighan CG, Hunger SP, Zhang J. Rise and Fall of Subclones from Diagnosis to Relapse in Pediatric B-Acute Lymphoblastic Leukemia. Nat Commun. 2015 Mar 19;6:6604. doi: 10.1038/ncomms7604. PMID: 25790293. PMCID: PMC4377644.

Roberts KG, Li Y, Payne-Turner D, Harvey RC, Yang YL, Pei D, McCastlain K, Ding L, Lu C, Song G, Ma J, Becksfort J, Rusch M, Chen SC, Easton J, Cheng J, Boggs K, Santiago-Morales N, Iacobucci I, Fulton RS, Wen J, Valentine M, Cheng C, Paugh SW, Devidas M, Chen IM, Reshmi S, Smith A, Hedlund E, Gupta P, Nagahawatte P, Wu G, Chen X, Yergeau D, Vadodaria B, Mulder H, Winick NJ, Larsen EC, Carroll WL, Heerema NA, Carroll AJ, Grayson G, Tasian SK, Moore AS, Keller F, Frei-Jones M, Whitlock JA, Raetz EA, White DL, Hughes TP, Guidry Auvil JM, Smith MA, Marcucci G, Bloomfield CD, Mrózek K, Kohlschmidt J, Stock W, Kornblau SM, Konopleva M, Paietta E, Pui CH, Jeha S, Relling MV, Evans WE, Gerhard DS, Gastier-Foster JM, Mardis E, Wilson RK, Loh ML, Downing JR, Hunger SP, Willman CL, Zhang J*, Mullighan CG. Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukemia. N Engl J Med 371(11):1005-15, 2014. PMID: 25207766. PMCID: PMC4191900. *Co-corresponding author.

Zhang J, G. Wu, Miller CP, Tatevossian RG, Dalton JD, Tang B, Orisme W, Punchihewa C, Qaddoumi I, Boop FA, Lu C, Kandoth C, Ding L, Parker M, Lee R, Huether R, Chen X, Hedlund E, Nagahawatte P, Rusch M, Boggs K, Cheng J, Becksfort J, Ma J, Song G, Li Y, Wei L, Wang J, Shurtleff S, Easton J, Zhao D, Fulton RS, Fulton LL, Dooling DJ, Vadodaria B, Mulder HL, Tang C, Ochoa K, Mullighan CG, Gajjar A, Kriwacki R, Sheer D, Gilbertson RJ, Mardis ER, Wilson RK, Downing JR, Baker SJ, Ellison DW.  Whole-genome sequencing identifies novel genetic alterations in pediatric low-grade gliomas. Nat Genet 45:602-612, 2013. PMID: 23583981. PMCID: PMC3727232.

Zhang J, Benavente CA, McEvoy J, Flores-Otero J, Ding L, Chen X, Ulyanov A, Wu G, Wilson M, Wang J, Brennan R, Rusch M, Manning AL, Ma J, Easton J, Shurtleff S, Mullighan C, Pounds S, Mukatira S, Gupta P, Neale G, Zhao D, Lu C, Fulton RS, Fulton LL, Hong X, Dooling DJ, Ochoa K, Naeve C, Dyson NJ, Mardis ER, Bahrami A, Ellison D, Wilson RK, Downing JR, Dyer MA. A novel retinoblastoma therapy from genomic and epigenetic analyses. Nature 481(7381):329-34, 2012.

Wu G, Broniscer A, McEachron TA, Lu C, Paugh BS, Becksfort J, Qu C, Ding L, Huether R, Parker M, Zhang J, Gajjar A, Dyer MA, Mullighan CG, Gilbertson RJ, Mardis ER, Wilson RK, Downing JR, Ellison DW, Zhang J, Baker SJ, St. Jude Children's Research Hospital–Washington University Pediatric Cancer Genome Project. Somatic histone H3 alterations in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas. Nat Genet 44(3):251-3, 2012.

Zhang J, Ding L, Holmfeldt L, Wu G, Heatley SL, Payne-Turner D, Easton J, Chen X, Wang J, Rusch M, Lu C, Chen SC, Wei L, Collins-Underwood JR, Ma J, Roberts KG, Pounds SB, Ulyanov A, Becksfort J, Gupta P, Huether R, Kriwacki RW, Parker M, McGoldrick DJ, Zhao D, Alford D, Espy S, Bobba KC, Song G, Pei D, Cheng C, Roberts S, Barbato MI, Campana D, Coustan-Smith E, Shurtleff SA, Raimondi SC, Kleppe M, Cools J, Shimano KA, Hermiston ML, Doulatov S, Eppert K, Laurenti E, Notta F, Dick JE, Basso G, Hunger SP, Loh ML, Devidas M, Wood B, Winter S, Dunsmore KP, Fulton RS, Fulton LL, Hong X, Harris CC, Dooling DJ, Ochoa K, Johnson KJ, Obenauer JC, Evans WE, Pui CH, Naeve CW, Ley TJ, Mardis ER, Wilson RK, Downing JR, Mullighan CG. The genetic basis of early T-cell precursor acute lymphoblastic leukaemia. Nature 481(7380):157-63, 2012.

Parker M, Chen X, Bahrami A, Dalton J, Rusch M, Wu G, Easton J, Cheung NK, Dyer M, Mardis ER, Wilson RK, Mullighan C, Gilbertson R, Baker SJ, Zambetti G, Ellison DW, Downing JR, Zhang J. Assessing telomeric DNA content in pediatric cancers using whole-genome sequencing data. Genome Biol 13(12):R113, 2012.

Wang J, Mullighan CG, Easton J, Roberts S, Heatley SL, Ma J, Rusch MC, Chen K, Harris CC, Ding L, Holmfeldt L, Payne-Turner D, Fan X, Wei L, Zhao D, Obenauer JC, Naeve C, Mardis ER, Wilson RK, Downing JR, Zhang J. CREST maps somatic structural variation in cancer genomes with base-pair resolution. Nature Methods 8(8):652-4, 2011.

Venter JC*, Adams MD, Myers EW, Li P, Mural RJ, Sutton GG, Smith HO, Yandell M, Evans CA, Holt RA, Gocayne JD, Amanatides P, Ballew RM, Huson D, Wortman JR, Zhang Q, Kodira C, Zheng X, Chen L, Skupski M, Subramanian G, Thomas PD, Zhang J, Gabor Miklos GL, Nelson C, Broder S, Clark AG, Nadeau J, McKusick VA, Zinder N, Levine AJ, Roberts R, Simon M, Hunkapiller M, Bolanos R, Delcher A, Dew I, Fasulo D, Flanigan M, Florea L, Halpern A, Hannenhalli S, Kravitz S, Levy S, Mobarry C, Reinert K, Remington K, Abu-Threideh J, Beasley E, Biddick K, Bonazzi V, Brandon R, Cargill M, Chandramouliswaran I, Charlab R, Chaturvedi K, Deng Z, Di Francesco V, Dunn P, Eilbeck K, Evangelista C, Gabrielian AE, Gan W, Ge W, Gong F, Gu Z, Guan P, Heiman TA, Higgins ME, Ji R-R, Ke Z, Ketchum KA, Lai Z, Lei Y, Li Z, Li J, Liang Y, Lin X, Lu F, Merkulov GV, Milshina N, Moore HM, Naik AK, Narayan VA, Neelam B, Nusskern D, Rusch DB, Salzberg S, Shao W, Shue B, Sun J, Wang AY, Wang A, Wang X, Wang J, Wei M-H, Wides R, Xiao C, Yan C, Yao A, Ye J, Zhan M, Zhang W, Zhang H, Zhao Q, Zheng L, Zhong F, Zhong W, Zhu SC, Zhao S, Gilbert D, Baumhueter S, Spier G, Carter C, Cravchik A, Woodage T, Ali F, An H, Awe A, Baldwin D, Baden H, Barnstead M, Barrow I, Beeson K, Busam D, Carver A, Center A, Cheng ML, Curry L, Danaher S, Davenport L, Desilets R, Dietz S, Dodson K, Doup L, Ferriera S, Garg N, Gluecksmann A, Hart B, Haynes J, Haynes C, Heiner C, Hladun S, Hostin D, Houck J, Howland T, Ibegwam C, Johnson J, Kalush F, Kline L, Koduru S, Love A, Mann F, May D, McCawley S, McIntosh T, McMullen I, Moy M, Moy L, Murphy B, Nelson K, Pfannkoch C, Pratts E, Puri V, Qureshi H, Reardon M, Rodriguez R, Rogers Y-H, Romblad D, Ruhfel B, Scott R, Sitter C, Smallwood M, Stewart E, Strong R, Suh E, Thomas R, Tint NN, Tse S, Vech C, Wang G, Wetter J, Williams S, Williams M, Windsor S, Winn-Deen E, Wolfe K, Zaveri J, Zaveri K, Abril JF, Guigó R, Campbell MJ, Sjolander KV, Karlak B, Kejariwal A, Mi H, Lazareva B, Hatton T, Narechania A, Diemer K, Muruganujan A, Guo N, Sato S, Bafna V, Istrail S, Lippert R, Schwartz R, Walenz B, Yooseph S, Allen D, Basu A, Baxendale J, Blick L, Caminha M, Carnes-Stine J, Caulk P, Chiang Y-H, Coyne M, Dahlke C, Mays AD, Dombroski M, Donnelly M, Ely D, Esparham S, Fosler C, Gire H, Glanowski S, Glasser K, Glodek A, Gorokhov M, Graham K, Gropman B, Harris M, Heil J, Henderson S, Hoover J, Jennings D, Jordan C, Jordan J, Kasha J, Kagan L, Kraft C, Levitsky A, Lewis M, Liu X, Lopez J, Ma D, Majoros W, McDaniel J, Murphy S, Newman M, Nguyen T, Nguyen N, Nodell M, Pan S, Peck J, Rowe W, Sanders R, Scott J, Simpson M, Smith T, Sprague A, Stockwell T, Turner R, Venter E, Wang M, Wen M, Wu D, Wu M, Xia A, Zandieh A, Zhu X. The Sequence of the Human Genome. Science 291:1145-1434, 2001.

Altschul SF, Madden TL, Schäffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 25:3389-3402, 1997.

Zhang J* , Hunter KW, Gandolph M, Rowe WL, Kelley JM, Edmonson M, Buetow KH.  A high-resolution multi-strain haplotype analysis of laboratory mouse genome reveals three distinctive genetic variation patterns.  Genome Res  15(2):241-249, 2005. PMID: 15687287. PMCID: PMC546525.

Last update: August 2016