Shen
Laboratory

Overview

Epigenomic Analysis in Human Disease

The Shen Laboratory focuses on the epigenome and its interaction with the genome in various diseases, with a specific emphasis on female cancers and cross-cancer comparisons. The Shen team uses bioinformatics as a tool to understand the etiology, cell of origin, and epigenetic mechanisms of various diseases and to devise better approaches for cancer prevention, detection, therapy, and monitoring. Team members have extensive experience with genome-scale DNA methylation profiles in primary human samples and have made major contributions to epigenetic analysis within The Cancer Genome Atlas (TCGA).

DNA methylation is ideally suited to deconstruct heterogeneity among cell types within a tissue sample. In cancer research, this approach can be used for both cancer cell clonal evolution studies or for quantifying normal cell infiltration and stromal composition. The latter can provide insights into the tumor microenvironment. For non-cancer studies, this method is a useful tool to accurately estimate different cell populations and provide insights into lineage structures and population shifts in disease. The Shen lab also is interested in translational applications of epigenomic technology. To this end, the lab translates markers that emerge from bioinformatics analysis into clinical assay development, marker panel assembly, and optimization, with the ultimate goal of clinical testing and validation.

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171 studies published from Nov. 1, 2020 to Oct. 1, 2021
68 studies in high-impact journals from Nov. 1, 2020-Oct. 1, 2021
41 clinical trials launched

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Hui Shen, Ph.D.

Associate Professor, Department of Epigenetics

Areas of Expertise

Epigenomics, DNA methylation, bioinformatics, ovarian cancer, pan-cancer comparison, genome-epigenome interaction

Biography

Dr. Shen received her B.Sc. in biology from Nanjing University and her Ph.D. in genetic, molecular, and cellular biology from the University of Southern California (USC) with a Provost PhD Fellowship. Dr. Shen has been part of The Cancer Genome Atlas team, a multi-institutional effort to better understand the molecular basis of cancer through genomic analysis. She joined VAI in September 2014 as an assistant professor and, in 2018, was promoted to associate professor. She is currently an F1000 Faculty Member for Cancer Epigenetics, and has been awarded the Liz Tilberis Award by Ovarian Cancer Research Alliance, an NIH/NCI ESI MERIT award and an AACR Team Science Award.

Pre-Print

Zhou W, Hinoue T, Barnes B, Mitchell O, Iqbal W, Lee SM, Foy KK, Lee KH, Moyer EJ, VanderArk A, Koeman JM, Ding W, Kalkat M, Spix NJ, Eagleson B, Pospisilik JA, Szabó PE, Bartolomei M, Vander Scaaf NA, Kang L, Wiseman AK, Jones PA, Krawczyk CM, Adams M, Porecha R, Chen BH, Shen H, Laird PW. Pre-print. DNA methylation dynamics and dysregulation delineated by high-throughput profiling in the mouse. BioRxiv.

Johnson BK, Fortin JP, Hansen KD, Shen H*, Triche TJ*. Pre-print. Compartmap enables inference of higher-order chromatin structure in individual cells from scRNA-seq and scATAC-seq. BioRxiv.
*Co-corresponding author

2021

Morrison J, Koeman JM, Johnson BK, Foy KK, Beddows I, Zhou W, Chesla DW, Rossell LL, Siegwald EJ, Adams M, Shen H. 2021. Evaluation of whole-genome DNA methylation sequencing library preparation protocols. Epigenetics Chromatin 14:28.

Wheeler DA, Takebe N, Hinoue T, Hoadley KA, Cardenas MF, Hamilton AM, Laird PW, Wang L, Johnson A, Dewal N, Miller V, Piñeyro D, Castro de Moura M, Esteller M, Shen H, Zenklusen JC, Tarnuzzer R, McShane LM, Tricoli JV, Williams PM, Lubensky I, O’Sullivan-Coyne G, Kohn EC, Little RF, White J, Malik S, Harris L, Weil C, Chen AP, Karlovich C, Rodgers B, Shankar L, Jacobs P, Nolan T, Hu J, Muzny DM, Doddapaneni H, Korchina V, Gastier-Foster J, Bowen J, Leraas K, Edmondson EF, Doroshow JH, Conley BA, Ivy SP, Staudt LM. 2021. Molecular features of cancers exhibiting exceptional responses to treatment. Can Cell 39(1):38–53.e7.

2020

Brieger KK, Peterson S, Lee AW, Mukherjee B, Bakulski KM, Alimujiang A, Anton-Culver H, Anglesio MS, Bandera EV, Berchuck A, Bowtell DDL, Chenevix-Trench G, Cho KR, Cramer DW, DeFazio A, Doherty JA, Fortner RT, Garsed DW, Gayther SA, Gentry-Maharaj A, Goode EL, Goodman MT, Harris HR, Høgdall E, Huntsman DG, Shen H, Jensen A, Johnatty SE, Jordan SJ, Kjaer SK, Kupryjanczyk J, Lambrechts D, McLean K, Menon U, Modugno F, Moysich K, Ness R, Ramus SJ, Richardson J, Risch H, Rossing MA, Trabert B, Wentzensen N, Ziogas A, Terry KL, Wu AH, Hanley GE, Pharoah P, Webb PM, Pike MC, Pearce CL. 2020. Menopausal hormone therapy prior to the diagnosis of ovarian cancer is associated with improved survival. Gynecol Oncol 158(3):702–709.

Conley BA, Staudt L, Takebe N, Wheeler DA, Wang L, Cardenas MF, Korchina V, Zenklusen JC, McShane LM, Tricoli JV, Williams PM, Lubensky I, O’Sullivan-Coyne G, Kohn E, Little RF, White J, Malik S, Harris LN, Mann B, Weil C, Tarnuzzer R, Karlovich C, Rodgers B, Shankar L, Jacobs PM, Nolan T, Berryman SM, Gastier-Foster J, Bowen J, Leraas K, Shen H, Laird PW, Esteller M, Miller V, Johnson A, Edmondson EF, Giordano TJ, Kim B, Ivy SP. 2020. The Exceptional Responders Initiative: Feasibility of A National Cancer Institute pilot study. J Natl Cancer Inst 113(1):27–37.

The ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium. 2020. Pan-cancer analysis of whole genomes. Nature 578(7793):82–93.
*Shen H is a coauthor through the ICGC consortium

Fan H, Atiya HI, Wang Y, Pisanic TR, Wang TH, Shih IM, Foy KK, Frisbie L, Buckanovich RJ, Chomiak AA, Tiedemann RL, Rothbart SB, Chandler C, Shen H, Coffman LG. 2020. Epigenomic reprogramming toward mesenchymal-epithelial transition in ovarian-cancer-associated mesenchymal stem cells drives metastasis. Cell Rep 33(10):108473.

Brown JR, Chan DK, Shank JJ, Griffith KA, Fan H, Szulawski R, Yang K, Reynolds RK, Johnston C, McLean K, Uppal S, Liu JR, Cabrera L, Taylor SE, Orr BC, Modugno F, Mehta P, Bregenzer M, Mehta G, Shen H, Coffman LG, Buckanovich RJ. 2020. Phase II clinical trial of metformin as a cancer stem cell–targeting agent in ovarian cancer. JCI Insight.

Carrot-Zhang J, Chambwe N, Damrauer JS, Knijnenburg TA, Robertson AG, Yau C, Zhou W, Berger AC, Huang K, Newberg JY, Mashl RJ, Romanel A, Sayaman RW, Demichelis F, Felau I, Frampton GM, Han S, Hoadley KA, Kemal A, Laird PW, Lazar AJ, Le X, Oak N, Shen H, Wong CK, Zenklusen JC, Ziv E. 2020. Comprehensive analysis of genetic ancestry and its molecular correlates in cancer. Can Cell 5(11):639–654.

2019

Gao GF, Parker, JS, Reynolds SM, Silva TC, Wang LB, Zhou W, Akbani R, Bailey M, Bale S, Berman BP, Brooks D, Chen H, Cherniak AD, Demchok JA, Ding J, Felau I, Gaheen S, Gergard DS, Heiman DI, Hernandez KM, Hoadley KA, Jayasinghe R, Kemal A, Knijnenburg TA, Laird PW, Menash MKA, Mungall AJ, Robertson AG, Shen H, Tarnuzzer R, Wang Z, Wyczalkowski M, Yang L, Zenklusen JC, Zhang Z, The Genomic Data Analysis Network, Liang H, Noble MS. 2019. Before and after: Comparison of legacy and harmonized TCGA Genomic Data Commons’ data. Cell Sys 9(1):24–34.

Wilson MR, Reske JJ, Holladay J, Wilber GE, Rhodes M, Koeman J, Adams M, Johnson B, Su RW, Joshi NR, Patterson AL, Shen H, Leach RE, Teixeria JM, Fazleabas AT, Chandler RL. 2019. ARID1A and PI3-kinase pathway mutations in the endometrium drive epithelial transdifferentiation and collective invasion. Nat Commun 10:3554.

George JW+, Fan H+, Johnson B, Carpenter TJ, Foy KK, Chatterjee A, Patterson AL, Koeman J, Adams M, Madaj ZB, Chesla D, Marsh EE, Triche TJ, Shen H*, Teixeira JM*. 2019. Integrated epigenome, exome, and transcriptome analyses reveal molecular subtypes and homeotic transformation in uterine fibroids. Cell Rep.
+ co-first authors; * co-senior authors

2018

Zhou W, Triche Jr. TJ, Laird PW, Shen H*. 2018. SeSAMe: reducing artifactual detection of DNA methylation by Infinium BeadChips in genomic deletions. Nuc Acids Res 46(20):e123-e123.
*senior author

Shen H+, Shih J, Hollern DP, Wang L, Bowlby R, Tickoo SK, Thorsson V … Hoadley KA. 2018. Integrated molecular characterization of testicular germ cell tumors. Cell Rep 23(11):3392–3406.
+ co-first authors

Sanchez-Vega F, Mina M, Armenia J…Zhou W, Shen H, Laird PW…Schultz N. 2018. Oncogenic signaling pathways in The Cancer Genome Atlas. Cell 173(2):321–337.
*One of three theme papers for the PanCancer Atlas

Berger AC, Korkut A, Kanchi RS…Fan H, Shen H…Akbani R. 2018. A comprehensive pan-cancer molecular study of gynecological and breast cancers. Can Cell 33(4):690–705.

Knijnenburg T, Wang L, Zimmerman MT, Chambwe N…Fan H, Shen H…Laird PW…Wang C. 2018. Genomic and molecular landscape of DNA damage repair deficiency across The Cancer Genome Atlas. Cell Rep 23(1):239–254.

Campbell JD, Yau C, Bowlby R, Liu Y, Brennan K, Fan H, Taylor AM, Wang C, Walter V, Akbani R, Byers LA, Creighton CJ, Coarfa C…Shen H…Laird PW…Waes CV. 2018. Genomic, pathway network, and immunologic features distinguishing squamous carcinomas. Cell Rep 23(1):194–212.

Ricketts CJ…Fan H…Shen H…Laird PW…Spellman P, Rathmell K, Linehan WM. 2018. Comprehensive molecular characterization of renal cell carcinoma. Cell Rep 23(1):313–326.

Thorsson V…Zhou W, Shen H…Shmulevich I. 2018. The immune landscape of cancer. Immunity 48(4):812–830.

Zhou W+, Dinh HQ+, Ramjan Z, Weisenberger DJ, Nicolet CM, Shen H*, Laird PW*, Berman BP*. 2018. DNA methylation loss in late-replicating domains is linked to mitotic cell division. Nat Gen 50:591–602.
+ co-first authors; * co-senior authors

2017

Zhou W, Laird PW, Shen H. 2017. Comprehensive characterization, annotation and innovative use of Infinium DNA methylation BeadChip probes. Nuc Acids Res 45(4):e22–e22.

The Cancer Genome Atlas Research Network. 2017. Comprehensive and integrative genomic characterization of hepatocellular carcinoma. Cell. 169(7):1327–1341.

Cherniack AD, Shen H…Laird PW…The Cancer Genome Atlas Research Network..Akbani R, Levine DA. 2017. Integrated molecular characterization of uterine carcinoma. Can Cell 31(3):411–423.

2016

The Cancer Genome Atlas Research Network. 2016. Comprehensive molecular characterization of papillary renal-cell carcinoma. New Eng J Med 374(2):135–145.

Gross AM, Jaeger PA, Kreisberg JF, Loncon K, Jepsen KL, Khosroheidari M, Morsey BM, Swindells S, Shen H, Ng CT, Flagg K, Chen D, Zhang K, Fox HS, Ideker T. 2016. Methylome-side analysis of chronic HIV infection reveals five-year increase in biological age and epigenetic targeting of HLA. Mol Cell 62(2):157–168.

Li B, Severson E, Pignon JC, Zhao H, Li T, Novak J, Jiang P, Shen H, Aster JC, Rodig S, Signoretti S, Liu JS, Liu XS. 2016. Comprehensive analyses of tumor immunity: implications for cancer immunotherapy. Genome Biol 17:174.

Liu M, Ohtani H, Zhou W, Ørskov AD, Charlet J, Zhang YW, Shen H, Baylin SB, Liang G, Grønbaek K, Jones PA. 2016. Vitamin C increases viral mimicry induced by 5-aza-2-deoxycytidine. Proc Natl Acad Sci USA 113(37):10238–10244.

Rhie SK, Guo Y, Tak YG, Yao L, Shen H, Coetzee GA, Laird PW, Farnham PJ. 2016. Identification of activated enhancers and linked transcription factors in breast, prostate, and kidney tumors by tracing enhancer networks using epigenetic traits. Epigenetics Chromatin 9:50.

Zhang X, Guo C, Wu X, Li AX, Liu L, Tsark W, Dammann R, Shen H, Vonderfecht SL, Pfeifer GP. 2016. Analysis of liver tumor–prone mouse models of the Hippo kinase scaffold proteins RASSF1A and SAV1. Cancer Res 76(9):2824–2935.

2015

The Cancer Genome Atlas Research Network. 2015. The molecular taxonomy of primary prostate cancer. Cell 163(4):1011–1025.

Ciriello G, Gatza ML, Beck AH, Wilkerson MD, Rhie SK, Pastore A, Zhang H, McLellan M, Yau C, Kandoth C, Bowlby R, Shen H, Hayat S, Fieldhouse R, Lester SC, Tse GMK, Factor RE, Collins LC, Allison KH, Chen YY, Jensen K, Johnson NB, Oesterreich S, Mills GB, Cherniack AD, Robertson G, Benz C, Sander C, Laird PW, Hoadley KA, King TA, TCGA Research Network, Perou CM. 2015. Comprehensive molecular portraits of invasive lobular breast cancer. Cell 163(2):506–519.

Yao L, Shen H, Laird PW, Farnham PJ, Berman BP. 2015. Inferring regulatory element landscapes and transcription factor networks from cancer methylomes. Genome Biol 16:105.

Cancer Genome Atlas Research Network*. 2015. Comprehensive, integrative genomic analysis of diffuse lower-grade gliomas. New Engl J Med 372(26):2481–2498.
*Shen H is one of 328 co-authors

2014

Davis CF, Ricketts CJ, Wang M, Yang L, Cherniack AD, Shen H, Buhay C, Kang H, Kim SC, Fahey CC, Hacker KE, Bhanot G, Gordenin DA, Chu A, Gunaratne PH, Biehl M, Seth S, Kaipparettu BA, Bristow CA, Donehower LA, Wallen EM, Smith AB, Tickoo SK, Tamboli P, Reuter V, Schmidt LS, Hsieh JJ, Choueiri TK, Hakimi AA, The Cancer Genome Atlas Research Network, Chin L, Meyerson M, Kucherlapati R, Park WY, Robertson AG, Laird PW, Henske EP, Kwiatkowski DJ, Park PJ, Morgan M, Shuch B, Muzny D, Wheeler DA, Linehan WM, Gibbs RA, Rathmell WK, and Creighton CJ. 2014. The somatic genomic landscape of chromophobe renal cell carcinoma. Can Cell 26(3):319–330.

Hoadley KA, Yau C, Wolf DM, Cherniack AD, Tamborero D, Ng S, Leiserson MD, Niu B, McLellan MD, Uzunangelov V, Zhang J, Kandoth C, Akbani R, Shen H, Omberg L, Chu A, Margolin AA, Van’t Veer LJ, Lopez-Bigas N, Laird PW, Raphael BJ, Ding L, Robertson AG, Byers LA, Mills GB, Weinstein JN, Van Waes C, Chen Z, Collisson EA, The Cancer Genome Atlas Research Network, Benz CC, Perou CM, and Stuart JM. 2014. Multiplatform analysis of 12 cancer types reveals molecular classification within and across tissues of origin. Cell 158(4):929–944.

Cancer Genome Atlas Research Network.* 2014. Comprehensive molecular characterization of gastric adenocarcinoma. Nature 513(7517):202–209.
*Shen H is one of 315 co-authors

The Cancer Genome Atlas Research Network.* 2014. Comprehensive molecular characterization of urothelial carcinoma of the bladder. Nature 507(7492): 315–322.
*Shen H is a coauthor.

2013

Ari Hakimi A, Furberg H, Zabor EC, Jacobsen A, Schultz N, Ciriello G, Mikklineni N, Fiegoli B, Kim PH, Voss MH, Shen H, Laird PW, Sander C, Reuter VE, Motzer RJ, Hsieh JJ, Russo P. 2013. An epidemiologic and genomic investigation into the obesity paradox in renal cell carcinoma. J Natl Can Inst 105(24):1862–1870.

Yoshihara K, Shahmoradgoli M, Martnez E, Vegesna R, Kim H, Torres-Garcia W, Trevino V, The Cancer Genome Atlas Research Network, Shen H, Laird PW, Levine DA, Carter SL, Getz G, Stemke-Hale K, Mills GB, Verhaak RGW. 2013. Estimating the presence of tumor-associated normal cells using gene expression signatures predicts tumor purity. Nat Comm 4:2612.

Zack TI, Schumacher SE, Carter SL, Cherniack AD, Saksena G, Tabak B, Lawrence MS, Zhang CZ, Wala J, Hermel CH, Sougnez C, Gabriel SB, Hernandez B, Shen H, Laird PW, Getz G, Meyerson M, Beroukhim R. 2013. Pan-cancer patterns of somatic copy number alteration. Nat Gen 45(10):1134–1140.

Cancer Genome Atlas Research Network; Genome Characterization Center, …, Shen H, Triche T,…, Stuart JM. 2013. The Cancer Genome Atlas Pan-Cancer analysis project. Nat Gen 45(10):1113–1120.

Cheng WY, Ou Yang TH, Shen H, Laird PW, Anastassiou D, The Cancer Genome Atlas Research Network. 2013. Multi-cancer molecular signatures and their interrelationships. arXiv:1306.2584.

The Cancer Genome Atlas Research Network.* 2013. Comprehensive molecular characterization of clear cell renal cell carcinoma. Nature 499(7456):43–49.
*Shen H is a coauthor and led DNA methylation analysis.

The Cancer Genome Atlas Research Network.* 2013. Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. New Eng J Med 368(22):2059–2074.
*Shen H is a coauthor

The Cancer Genome Atlas Research Network, Kandoth C, Schultz N, Cherniack AD, Akbani R, Liu Y, Shen H, Robertson AG, Pashtan I, Shen R, Benz CC, Yau C, Laird PW, Ding L, Zhang W, Mills GB, Kucherlapati R, Mardis ER, Levine DA. 2013. Integrated genomic characterization of endometrial carcinoma. Nature 497(7447):67–73.

Shen H, Laird PW. 2013. Interplay between the cancer genome and epigenome. Cell 153(1):38–55.

Pharoah PD, …, Shen H,…, Sellers TA. 2013. GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian cancer. Nat Gen 45(4):362–370.

Shen H,…, Laird PW, Goode EL, Leigh Pearce C. 2013. Epigenetic analysis leads to identification of HNF1B as a subtype-specific susceptibility gene for ovarian cancer. Nat Comm 4:1628.

2012

Lange CP, Campan M, Hinoue T, Schmitz RF, van der Meulen-de Jong AE, Slingerland H, Kok PJ, van Dijk CM, Weisenberger DJ, Shen H, Tollenaar RA, Laird PW. 2012. Genome-scale discovery of DNA-methylation biomarkers for blood-based detection of colorectal cancer. PLoS One 7(11):e50266.

The Cancer Genome Atlas Network.* 2012. Comprehensive molecular portraits of human breast tumors. Nature 490(7418):61–70.
*Shen H is a coauthor.

Zhang S, Liu CC, Li W, Shen H, Laird PW, Zhou XJ. 2012. Discovery of multi-dimensional modules by integrative analysis of cancer genomic data. Nuc Acids Res 40(19):9379–9391.

The Cancer Genome Atlas Network.* 2012. Comprehensive molecular characterization of human colon and rectal cancer. Nature 487(7407):330–337.
*Shen H is a coauthor.

Carter SL, Cibulskis K*, Helman E*, McKenna A*, Shen H*, Zack T*, Laird PW, Onofrio RC, Winckler W, Weir BA, Beroukhim R, Pellman D, Levine DA, Lander ES, Meyerson M, Getz G. 2012. Absolute quantification of somatic DNA alterations in human cancer. Nat Biotech 30(5):413–421.
*These authors contributed equally to the work.

Shen H, Laird PW. 2012. In epigenetic therapy, less is more. Cell Stem Cell 10(4):353–354.

2011

Campan M, Moffitt M, Houshdaran S, Shen H, Widschwendter M, Daxenbichler G, Long T, Marth C, Laird-Offringa IA, Press MF, Dubeau L, Siegmund KD, Wu AH, Groshen S, Chandavarkar U, Roman LD, Berchuck A, Pearce CL, Laird PW. 2011. Genome-scale screen for DNA methylation-based detection markers for ovarian cancer. PLoS One 29(12):1132–1144.

International Stem Cell Initiative,…, Laird PW, …, Shen H, …, Zhou Q. 2011. Screening ethnically diverse human embryonic stem cells identifies a chromosome 20 minimal amplicon conferring growth advantage. Nat Biotech 29(12):1132–1144.

Hinoue T, Weisenberger DJ, Lange CP, Shen H, Byun HM, Van Den Berg D, Malik S, Pan F, Noushmehr H, van Dijk CM, Tollenaar RA, Laird PW. 2012. Genome-scale analysis of aberrant DNA methylation in colorectal cancer. Gen Res 22(2):271–282.

The Cancer Genome Atlas Research Network. 2011. Integrated genomic analyses of ovarian carcinoma. Nature 474(7353):609–615.
*Shen H is a coauthor and led the DNA methylation analysis.

Oghamian S, Sodir NM, Bashir MU, Shen H, Cullins AE, Carroll CA, Kundu P, Shibata D, Laird PW. 2011. Reduction of pancreatic acinar cell tumor multiplicity in Dnmt1 hypomorphic mice. Carcinogen 32(6):829–835.

Noushmehr H,Weisenberger DJ, Diefes K, Phillips HS, Pujara K, Berman BP, Pan F, Pelloski CE, Sulman EP, Bhat KP, Verhaak RG, Hoadley KA, Hayes DN, Perou CM, Schmidt HK, Ding L, Wilson RK, Van Den Berg D, Shen H, Bengtsson H, Neuvial P, Cope LM, Buckley J, Herman JG, Baylin SB, Laird PW, Aldape K; Cancer Genome Atlas Research Network. 2010. Identification of a CpG island methylator phenotype that defines a distinct subgroup of glioma. Can Cell 17(5):510–522.

Teschendorff AE, Menon U, Gentry-Maharaj A, Ramus SJ, Weisenberger DJ, Shen H, Campan M, Noushmehr H, Bell CG, Maxwell AP, Savage DA, Mueller-Holzner E, Marth C, Kocjan G, Gayther SA, Jones A, Beck S, Wagner W, Laird PW, Jacobs IJ, Widschwendter M. 2010. Age-dependent DNA methylation of genes that are suppressed in stem cells is a hallmark of cancer. Gen Res 20(4):440–446.