Ronglai Shen, PhD

Associate Attending Biostatistician

Office Phone

646-888-8243

Email

shenr@mskcc.org

Education

University of Michigan

Current Research Interests

Dr. Shen’s research interest lies in developing statistical and computational genomics approaches and applications to translational cancer research. She has developed data integration methods for defining molecular subtypes of cancer and associated biomarkers across multiple “omic” data types simultaneously characterizing genomic, epigenomic, transcriptomic, and proteomic aberrations in a tumor. Her method has been used for integrative subtype analysis of breast, prostate, lung, stomach, endometrial, skin, and liver cancer in large-scale cancer genome consortium studies including the NCI/NHGRI Cancer Genome Atlas (TCGA) and the Canada-UK Molecular Taxonomy of Breast Cancer International Consortium (METABRIC). Her recent work focuses on tumor clonal heterogeneity analysis. Together with Dr. Venkatraman Seshan, she has developed methods to unravel allele-specific copy number aberrations and clonal heterogeneity within a tumor from DNA sequencing of tumor-normal pairs that can be applied to whole-genome, whole-exome and capture sequencing platforms. Its application has shed light on the clonal status of somatic mutations and copy number alterations in lung and breast cancers as a biomarker for disease progression. Her recent research interest also includes basket trial design for biomarker-driven clinical trials in collaboration with Drs. Kristen Cunanan, Mithat Gonen, Colin Begg, and Alexia Iasonos.

Publications

Shen R, Olshen AB, Ladanyi M. (2009) Integrative clustering of multiple genomic data types using a joint latent variable model with application to breast and lung cancer subtype analysis. Bioinformatics. 25:2906-12. PMCID: PMC2800366

Shen R, Wang S, Mo Q. (2012) Sparse integrative clustering of multiple omics data sets. Annals of Applied Statistics. 7:269-294. PMCID: PMC3935438

Mo Q, Wang S, Seshan VE, Olshen AB, Schultz N, Sander C, Powers RS, Ladanyi M, and Shen R*. (2013) Pattern discovery and cancer gene identification in integrated cancer genomic data. Proceedings of National Academy of Sciences U S A. 110:4245-50. PMCID: PMC3600490. *Corresponding author

Cancer Genome Atlas Research Network (R. Shen co-author). (2014) Comprehensive molecular profiling of lung adenocarcinoma. Nature. 511:543-550.

Paik PK, Shen R*, Won H, Rekhtman N, Wang L, Sima CS, Arora A, Seshan, V, Ladanyi M, Berger MF and Kris, MG. (2015) Next generation sequencing of stage IV squamous cell lung cancers reveals an association of PI3K aberrations and evidence of clonal heterogeneity in patients with brain metastasesCancer Discovery. 5(6):610-21. * Co-first author.

Shen R, Seshan VE. (2016) FACETS: allele-specific copy number and clonal heterogeneity analysis tool for high-throughput DNA sequencing. Nucleic Acids Res. 44(16):e131

Cunanan KM, Gonen M, Shen R, Hyman DM, Riely GJ, Begg CB, Iasonos A. (2016) Basket Trials in Oncology: A Trade-Off Between Complexity and Efficiency. J Clin Oncol. [Epub ahead of print]

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  1. Dash A, Maine IP, Varambally S, Shen R, Chinnaiyan AM, Rubin MA. Changes in differential gene expression because of warm ischemia time of radical prostatectomy specimens. American Journal of Pathology 2002; 161:1743-1748. [PubMed Abstract]

  2. Zhou M, Shah R, Shen R, Rubin MA. Basal cell cocktail (34betaE12 + p63) improves the detection of prostate basal cells. American Journal of Clinical Pathology 2003; 27(3):365-71.

  3. Kleer CG, Cao Q, Varambally S, Shen R, Ota I, Tomlins SA, Ghosh D, Sewalt RG, Otte AP, Hayes DF, Sabel MS, Livant D, Weiss SJ, Rubin MA, Chinnaiyan AM. EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells. Proceedings of the National Academy of Sciences 2003; 100:11606-11611. [PubMed Abstract]

  4. Hofer MD, Fecko A, Shen R, Setlur SR, Pienta KG, Tomlins SA, Chinnaiyan AM, Rubin MA. Expression of the platelet-derived growth factor receptor in prostate cancer and  treatment implications with tyrosine kinase inhibitors. Neoplasia 2004; 6(5):503-12.

  5. Shah RB, Kunju LP, Shen R, LeBlanc M, Zhou M, Rubin MA. Usefulness of basal cell cocktail (34betaE12 + p63) in the diagnosis of atypical  prostate glandular proliferations. American Journal of Clinical Pathology 2004;122(4):517-23.

  6. Shen R, Ghosh D, Chinnaiyan A. Prognostic meta-signature of breast cancer developed by two-stage mixture modeling of microarray data. BMC Genomics 2004; 5:94. [PubMed Abstract]

  7. Shah RB, Mehra R, Chinnaiyan AM, Shen R, Ghosh D, Zhou M, Macvicar GR, Varambally S, Harwood J, Bismar TA, Kim R, Rubin MA, Pienta KJ. Androgen-independent prostate cancer is a heterogeneous group of diseases: Lessons from a rapid autopsy program. Cancer Research 2004; 64:9209-9216.

  8. Kwak SH, Shen R, Schiefelbein J. Positional signaling mediated by a receptor-like kinase in Arabidopsis. Science 2005; 307(5712):1111-3.

  9. Witkiewicz AK, Varambally S, Shen R, Mehra R, Sabel MS, Ghosh D, Chinnaiyan AM, Rubin MA, Kleer CG. Alpha-methylacyl-CoA racemase protein expression is associated with the degree of differentiation in breast cancer using quantitative image analysis. Cancer Epidemiology and Biomarkers Prevention 2005;14(6):1418-23.

  10. Rubin MA, Bismar TA, Andrén O, Mucci L, Kim R, Shen R, Ghosh D, Wei JT, Chinnaiyan AM, Adami HO, Kantoff PW, Johansson JE. Decreased alpha-methylacyl CoA racemase expression in localized prostate cancer is associated with an increased rate of biochemical recurrence and cancer-specific death. Cancer Epidemiology and Biomarkers Prevention 2005;14(6):1424-32.

  11. Wang X, Yu J, Sreekumar A, Varambally S, Shen R, Giacherio D, Mehra R, Montie JE, Pienta KJ, Sanda MG, Kantoff PW, Rubin MA, Wei JT, Ghosh D, Chinnaiyan AM. Autoantibody signatures in prostate cancer. New England Journal of Medicine 2005; 353:1224-1235.

  12. Mehra R, Varambally S, Ding L, Shen R, Sabel MS, Ghosh D, Chinnaiyan AM, Kleer CG. Identification of GATA3 as a breast cancer prognostic marker by global gene expression meta-analysis. Cancer Research 2005; 65:11259-11264.

  13. Kim R, Demichelis F, Tang J, Riva A, Shen R, Gibbs DF, Mahavishno V, Chinnaiyan AM, Rubin MA. Internet-based profiler system as integrative framework to support translational research. BMC Bioinformatics 2005; 6:304. [PubMed Abstract]

  14. Fu Z, Kitagawa Y, Shen R, Shah R, Mehra R, Rhodes D, Keller PJ, Mizokami A, Dunn R, Chinnaiyan AM, Yao Z, Keller ET. Metastasis suppressor gene raf kinase inhibitor protein (RKIP) is a novel prognostic marker in prostate cancer. Prostate 2006; 66:248-256.

  15. Shen R, Ghosh D, Chinnaiyan AM, Meng Z. Eigengene based linear discriminant model for gene expression data analysis. Bioinformatics 2006; 22: 2635-2642.

  16. Mehra R, Tomlins SA, Shen R, Nadeem O, Wang L, Wei JT, Pienta KJ, Ghosh D, Rubin MA, Chinnaiyan AM, Shah RB. Comprehensive assessment of TMPRSS2 and ETS family gene aberrations in clinically localized prostate cancer. Modern Pathology 2007; 20: 538-544.

  17. Mehra R, Han B, Tomlins SA, Wang L, Menon A, Wasco MJ, Shen R, Montie JE, Chinnaiyan AM, Shah RB. Heterogeneity of TMPRSS2 gene rearrangements in multifocal prostate adenocarcinoma: molecular evidence for an independent group of diseases. Cancer Research 2007; 67: 7991-7995.

  18. Choi H, Shen R, Chinnaiyan Am, Ghosh D. A latent variable approach for meta-analysis of gene expression data from multiple microarray experiments. BMC Bioinformatics 2007; 8: 364. [PubMed Abstract]

  19. Yu J, Cao Q, Mehra R, Laxman B, Yu J, Tomlins SA, Creighton CJ, Dhanasekaran SM, Shen R, Chen G, Morris DS, Marquez VE, Shah RB, Ghosh D, Varambally S, Chinnaiyan AM. Integrative genomics analysis reveals silencing of beta-adrenergic signaling by polycomb in prostate cancer. Cancer Cell 2007;12(5):419-31.

  20. Shen R, Ghosh D, Taylor JM. Modeling intra-tumor protein expression heterogeneity in tissue microarray experiments. Statistics in Medicine 2008; 27(11):1944-59. [PubMed Abstract]

  21. Shen R, Chinnaiyan AM, Ghosh D. Pathway analysis reveals functional convergence of gene expression profiles in breast cancer. BMC Medical Genomics 2008;1:28. [PubMed Abstract]

  22. Shen R, Taylor JM, Ghosh D. Reconstructing tumor-wise protein expression in tissue microarray studies using a Bayesian cell mixture model. Bioinformatics 2008; 24(24):2880-6.

  23. Varambally S, Laxman B, Mehra R, Cao Q, Dhanasekaran SM, Tomlins SA, Granger J, Vellaichamy A, Sreekumar A, Yu J, Gu W, Shen R, Ghosh D, Wright LM, Kladney RD, Kuefer R, Rubin MA, Fimmel CJ, Chinnaiyan AM. Golgi protein GOLM1 is a tissue and urine biomarker of prostate cancer. Neoplasia 2008; 10(11):1285-94. [PubMed Abstract]

  24. Gong Y, Yao E, Shen R, Goel A, Arcila M, Teruya-Feldstein J, Zakowski MF, Frankel S, Peifer M, Thomas RK, Ladanyi M, Pao W. Expression levels of total IGF-1R and sensitivity of NSCLC cells in vitro to an anti-IGF-1R antibody (R1507). PLoS ONE 2009; 4(10): e7273.

  25. Regales L, Gong Y, Shen R, Stanchina E, Vivanco I, Goel A, Koutcher JA, Spassova M, Ouerfelli O, Mellinghoff IK, Zakowski MF, Politi KA, Pao W. Novel dual targeting of EGFR can overcome a major drug resistance mutation in EGFR-mutant lung cancer. Journal of Clinical Investigation 2009; 119(10):3000-10.

  26. Girard N, Shen R, Guo T, Zakowski MF, Heguy A, Riely GJ, Huang J, Lau C, Lash AE, Ladanyi M, Viale A, Antonescu CR, Travis WD, Rusch VW, Kris MG, Pao W. Comprehensive genomic analysis reveals clinically relevant molecular distinctions between thymic carcinomas and thymomas. Clinical Cancer Research 2009;15(22):6790-9.

  27. Shen R, Olshen AB, Ladanyi M. Integrative Clustering of multiple genomic data types using a joint latent variable model with application to breast and lung cancer subtype analysis. Bioinformatics 2009; 25(22): 2906-12.

  28. Politi K, Fan PD, Shen R, Zakowski M, Varmus H. Erlotinib resistance in mouse  models of epidermal growth factor receptor-induced lung adenocarcinoma. Dis Model Mech. 2010; 3(1-2):111-9.

  29. Janjigian YY, McDonnell K, Kris MG, Shen R, Sima CS, Bach PB, Rizvi NA, Riely  GJ. Pack-years of cigarette smoking as a prognostic factor in patients with stage IIIB/IV nonsmall cell lung cancer. Cancer. 2010; 116 (3):670-5.

  30. Fury MG, Haque S, Stambuk H, Shen R, Carlson D, Pfister D. A phase 2 study of pemetrexed plus gemcitabine every 2 weeks for patients with recurrent or metastatic head and neck squamous cell cancer. Cancer. 2011;117(4):795-801.

  31. Janjigian YY, Park BJ, Zakowski MF, Ladanyi M, Pao W, Dangelo SP, Kris MG, Shen R, Zheng J, Azzoli CG. Impact on Disease-Free Survival of Adjuvant Erlotinib or Gefitinib in Patients with Resected Lung Adenocarcinomas that Harbor EGFR Mutations. J Thorac Oncol. 2011;6(3):569-75.

  32. Fang F, Turcan S, Rimner A, Kaufman A, Giri D, Morris LG, Shen R, Seshan V, Mo Q, Heguy A, Baylin SB, Ahuja N, Viale A, Massague J, Norton L, Vahdat LT, Moynahan ME, Chan TA.  Breast cancer methylomes establish an epigenomic foundation for metastasis. Science Translation Medicine 2011;3(75):75ra25. 23 [PubMed Abstract]

  33. Mankoo PK, Shen R, Schultz N, Levine DA, Sander C. Time to recurrence and survival in serous ovarian tumors predicted from integrated genomic profiles. PLoS One. 2011; 6: e24709

  34. Bott M, Brevet M, Taylor BS, Shimizu S, Ito T, Wang L, Creaney J, Lake RA, Zakowski MF, Reva B, Sander C, Delsite R, Powell S, Zhou Q, Shen R, Olshen A, Rusch V, Ladanyi M. The nuclear deubiquitinase BAP1 is commonly inactivated by somatic mutations and 3p21.1 losses in malignant pleural mesothelioma. Nature Genetics. 2011 5, 668-72

  35. Dogan S, Shen R, Ang DC, Johnson ML, D’Angelo SP, Paik PK, Brzostowski EB, Riely GJ, Kris MG, Zakowski MF, Ladanyi M. Molecular epidemiology of EGFR and KRAS mutations in 3,026 lung adenocarcinomas: higher susceptibility of women to smoking-related KRAS-mutant cancers. Clin Cancer Res. 2012; 18: 6169-77

  36. Gorovets D, Kannan K, Shen R, Kastenhuber ER, Islamdoust N, Campos C, Pentsova E, Heguy A, Jhanwar SC, Mellinghoff IK, Chan TA, Huse JT. IDH mutation and neuroglial developmental features define clinically distinct subclasses of lower grade diffuse astrocytic glioma. Clin Cancer Res. 2012; 18: 2490-501

  37. Vakiani E, Janakiraman M, Shen R, Sinha R, Zeng Z, Shia J, Cercek A, Kemeny N, D’Angelica M, Viale A, Heguy A, Paty P, Chan TA, Saltz LB, Weiser M, Solit DB. Comparative Genomic Analysis of Primary Versus Metastatic Colorectal Carcinomas. J Clin Oncol. 2012; 20:2956-62 [PubMed Abstract]

  38. Gao H, Chakraborty G, Lee-Lim AP, Mo Q, Decker M, Vonica A, Shen R, Brogi E, Brivanlou AH, Giancotti FG. The BMP inhibitor Coco reactivates breast cancer cells at lung metastatic sites. Cell 2012; 17: 764-79.

  39. Shen R, Mo Q, Schultz N, Seshan VE, Olshen AB, Huse J, Ladanyi M, Sander C. Integrative subtype discovery in glioblastoma using iCluster. PLoS One. 2012: 7(4):e35236. [PubMed Abstract]

  40. Shen R, Wang S, Mo Q. (2012). Sparse integrative clustering of multiple omics data sets. Annals of Applied Statistics. (In Press). NIHMSID: NIHMS402415.

  41. Cancer Genome Atlas Network.  Comprehensive molecular characterization of human colon and rectal cancer. Nature 2012; 487: 330-7

  42. Cancer Genome Atlas Network.  Comprehensive molecular portraits of human breast tumours. Nature. 2012; 490: 61-70.

  43. Hammerman PS, Hayes DN, Wilkerson MD, Schultz N, Bose R, Chu A, Collisson EA, Cope L, Creighton CJ, Getz G, Herman JG, Johnson BE, Kucherlapati R, Ladanyi M, Maher CA, Robertson G, Sander C, Shen R, Sinha R, Sivachenko A, Thomas RK, Travis WD, Tsao MS, Weinstein JN, Wigle DA, Baylin SB, Govindan R, Meyerson M. Comprehensive genomic characterization of squamous cell lung cancers. Cancer Genome Atlas Research Network. Nature. 2012; 27: 519-25.

  44. D’Angelo SP, Janjigian YY, Ahye N, Riely GJ, Chaft JE, Sima CS, Shen R, Zheng J, Dycoco J, Kris MG, Zakowski MF, Ladanyi M, Rusch V, Azzoli CG.  Distinct clinical course of EGFR-mutant resected lung cancers: results of testing of 1118 surgical specimens and effects of adjuvant gefitinib and erlotinib. J Thorac Oncol. 2012;7:1815-22.

  45. Mo Q, Wang S, Seshan VE,  Olshen AB, Schultz N, Sander C, Powers RS, Ladanyi M, Shen R*.  Pattern discovery and cancer gene identification in integrated cancer genomic data. Proceedings of the National Academy of Sciences. 2013(In Press). *Corresponding author

 

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