Photo of Toshihiro Shioda,  MD, PhD

Toshihiro Shioda, MD, PhD

Massachusetts General Hospital

Massachusetts General Hospital
Phone: (617) 726-3425
Fax: (617) 726-5637

Toshihiro Shioda, MD, PhD

Massachusetts General Hospital


  • Associate Professor, Medicine, Harvard Medical School
  • Member, MGH Cancer Center, Massachusetts General Hospital


Research Abstract

My laboratory has been working on the following areas of studies.

(i) Roles and mechanisms of actions of estrogens and antiestrogens in human breast cancer. [MCF-7 cell culture and its monoclonal sublines with different sensitivities to antiestrogens; The TRC shRNA lentivirus library; high-throughput RNAi knockdown screening; Affymetrix microarray]

(ii) Pharmacogenomics and Toxicogenomics of estrogens and xenobiotic environmental estrogenic substances. [MCF-7 cell culture; Affymetrix microarray, high-throughput RT-qPCR; computational biology]

(iii) Exposure of fetuses to the environmental substances and bioactive food compoents during their early stages of developement: Effects on epigenetic gene regulation and breast cancer risk. [rat fetuses, chicken embryos, zebrafish embryos, DNA methylation, bisulfite sequencing, ultradeep parallel sequencing, Affymetrix microarray, high-throughput RT-qPCR]

(iv) Toxicological servey on the environmental contamination by estrogenic xenoestrogens. [MCF-7 cell culture, RT-qPCR]


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  • Sarioglu AF, Aceto N, Kojic N, Donaldson MC, Zeinali M, Hamza B, Engstrom A, Zhu H, Sundaresan TK, Miyamoto DT, Luo X, Bardia A, Wittner BS, Ramaswamy S, Shioda T, Ting DT, Stott SL, Kapur R, Maheswaran S, Haber DA, Toner M. A microfluidic device for label-free, physical capture of circulating tumor cell clusters. Nat Methods 2015; 12:685-91. PubMed
  • Javaid S, Zhang J, Smolen GA, Yu M, Wittner BS, Singh A, Arora KS, Madden MW, Desai R, Zubrowski MJ, Schott BJ, Ting DT, Stott SL, Toner M, Maheswaran S, Shioda T, Ramaswamy S, Haber DA. MAPK7 regulates EMT Features and Modulates the Generation of CTCs. Mol Cancer Res 2015. PubMed
  • Niederst MJ, Sequist LV, Poirier JT, Mermel CH, Lockerman EL, Garcia AR, Katayama R, Costa C, Ross KN, Moran T, Howe E, Fulton LE, Mulvey HE, Bernardo LA, Mohamoud F, Miyoshi N, VanderLaan PA, Costa DB, Jänne PA, Borger DR, Ramaswamy S, Shioda T, Iafrate AJ, Getz G, Rudin CM, Mino-Kenudson M, Engelman JA. RB loss in resistant EGFR mutant lung adenocarcinomas that transform to small-cell lung cancer. Nat Commun 2015; 6:6377. PubMed
  • Friel AM, Zhang L, Pru CA, Clark NC, McCallum ML, Blok LJ, Shioda T, Peluso JJ, Rueda BR, Pru JK. Progesterone receptor membrane component 1 deficiency attenuates growth while promoting chemosensitivity of human endometrial xenograft tumors. Cancer Lett 2014. PubMed
  • Yu M, Bardia A, Aceto N, Bersani F, Madden MW, Donaldson MC, Desai R, Zhu H, Comaills V, Zheng Z, Wittner BS, Stojanov P, Brachtel E, Sgroi D, Kapur R, Shioda T, Ting DT, Ramaswamy S, Getz G, Iafrate AJ, Benes C, Toner M, Maheswaran S, Haber DA. Cancer therapy. Ex vivo culture of circulating breast tumor cells for individualized testing of drug susceptibility. Science 2014; 345:216-20. PubMed
  • Liu M, Roth A, Yu M, Morris R, Bersani F, Rivera MN, Lu J, Shioda T, Vasudevan S, Ramaswamy S, Maheswaran S, Diederichs S, Haber DA. The IGF2 intronic miR-483 selectively enhances transcription from IGF2 fetal promoters and enhances tumorigenesis. Genes Dev 2013; 27:2543-8. PubMed
  • Corcoran RB, Cheng KA, Hata AN, Faber AC, Ebi H, Coffee EM, Greninger P, Brown RD, Godfrey JT, Cohoon TJ, Song Y, Lifshits E, Hung KE, Shioda T, Dias-Santagata D, Singh A, Settleman J, Benes CH, Mino-Kenudson M, Wong KK, Engelman JA. Synthetic lethal interaction of combined BCL-XL and MEK inhibition promotes tumor regressions in KRAS mutant cancer models. Cancer Cell 2013; 23:121-8. PubMed
  • Taylor JA, Richter CA, Suzuki A, Watanabe H, Iguchi T, Coser KR, Shioda T, Vom Saal FS. Dose-related estrogen effects on gene expression in fetal mouse prostate mesenchymal cells. PLoS ONE 2012; 7:e48311. PubMed
  • Ishii Y, Papa L, Bahadur U, Yue Z, Aguirre-Ghiso JA, Shioda T, Waxman S, Germain D. Bortezomib enhances the efficacy of fulvestrant by amplifying the aggregation of the estrogen receptor, which leads to a pro-apoptotic unfolded protein response. Clin Cancer Res 2011. PubMed
  • Dittmer S, Kovacs Z, Yuan SH, Siszler G, Kögl M, Summer H, Geerts A, Golz S, Shioda T, Methner A. TOX3 is a neuronal survival factor that induces transcription depending on the presence of CITED1 or phosphorylated CREB in the transcriptionally active complex. J Cell Sci 2010; 124:252-60. PubMed
  • Polo JM, Liu S, Figueroa ME, Kulalert W, Eminli S, Tan KY, Apostolou E, Stadtfeld M, Li Y, Shioda T, Natesan S, Wagers AJ, Melnick A, Evans T, Hochedlinger K. Cell type of origin influences the molecular and functional properties of mouse induced pluripotent stem cells. Nat Biotechnol 2010; 28:848-55. PubMed
  • Walker AK, Yang F, Jiang K, Ji JY, Watts JL, Purushotham A, Boss O, Hirsch ML, Ribich S, Smith JJ, Israelian K, Westphal CH, Rodgers JT, Shioda T, Elson SL, Mulligan P, Najafi-Shoushtari H, Black JC, Thakur JK, Kadyk LC, Whetstine JR, Mostoslavsky R, Puigserver P, Li X, Dyson NJ, Hart AC, Näär AM. Conserved role of SIRT1 orthologs in fasting-dependent inhibition of the lipid/cholesterol regulator SREBP. Genes Dev 2010; 24:1403-17. PubMed
  • Chen L, Shioda T, Coser KR, Lynch MC, Yang C, Schmidt EV. Genome-wide analysis of YY2 versus YY1 target genes. Nucleic Acids Res 2010; 38:4011-26. PubMed
  • Najafi-Shoushtari SH, Kristo F, Li Y, Shioda T, Cohen DE, Gerszten RE, Näär AM. MicroRNA-33 and the SREBP host genes cooperate to control cholesterol homeostasis. Science 2010; 328:1566-9. PubMed
  • Stadtfeld M, Apostolou E, Akutsu H, Fukuda A, Follett P, Natesan S, Kono T, Shioda T, Hochedlinger K. Aberrant silencing of imprinted genes on chromosome 12qF1 in mouse induced pluripotent stem cells. Nature 2010; 465:175-81. PubMed
  • Wolfer A, Wittner BS, Irimia D, Flavin RJ, Lupien M, Gunawardane RN, Meyer CA, Lightcap ES, Tamayo P, Mesirov JP, Liu XS, Shioda T, Toner M, Loda M, Brown M, Brugge JS, Ramaswamy S. MYC regulation of a "poor-prognosis" metastatic cancer cell state. Proc Natl Acad Sci U S A 2010; 107:3698-703. PubMed
  • Hayashida T, Takahashi F, Chiba N, Brachtel E, Takahashi M, Godin-Heymann N, Gross KW, Vivanco MM, Wijendran V, Shioda T, Sgroi D, Donahoe PK, Maheswaran S. HOXB9, a gene overexpressed in breast cancer, promotes tumorigenicity and lung metastasis. Proc Natl Acad Sci U S A 2010; 107:1100-5. PubMed
  • Coser KR, Wittner BS, Rosenthal NF, Collins SC, Melas A, Smith SL, Mahoney CJ, Shioda K, Isselbacher KJ, Ramaswamy S, Shioda T. Antiestrogen-resistant subclones of MCF-7 human breast cancer cells are derived from a common monoclonal drug-resistant progenitor. Proc Natl Acad Sci U S A 2009; 106:14536-41. PubMed
  • Montagut C,Sharma SV,Shioda T,McDermott U,Ulman M,Ulkus LE,Dias-Santagata D,Stubbs H,Lee DY,Singh A,Drew L,Haber DA,Settleman J. Elevated CRAF as a potential mechanism of acquired resistance to BRAF inhibition in melanoma. Cancer Res 2008; 68:4853-61. PubMed
  • McDermott U, Iafrate AJ, Gray NS, Shioda T, Classon M, Maheswaran S, Zhou W, Choi HG, Smith SL, Dowell L, Ulkus LE, Kuhlmann G, Greninger P, Christensen JG, Haber DA, Settleman J. Genomic alterations of anaplastic lymphoma kinase may sensitize tumors to anaplastic lymphoma kinase inhibitors. Cancer Res 2008; 68:3389-95. PubMed
  • Yang D, Guo J, Divieti P, Shioda T, Bringhurst FR. CBP/P300-Interacting Protein CITED1 Modulates PTH Regulation of Osteoblastic Differentiation. Endocrinology 2008; 149:1728-35. PubMed
  • Sakuragi J, Sakuragi S, Ohishi M, Shioda T. A rapid recombination assay of HIV-1 using murine CD52 as a novel biomarker. Microbes Infect 2008; 10:396-404. PubMed
  • Louisirirotchanakul S, Sutthent R, Wasi C, Chuenchitra T, Nitayaphan S, Brown AE, Polonis VR, Nakayama EE, Shioda T, Liu H, Takebe Y. Host genetic analysis of HIV type 1 subtype CRF01_AE (E)-infected Thai patients with different rates of disease progression. AIDS Res Hum Retroviruses 2007; 23:1605-8. PubMed
  • Nelson GM, Padera TP, Garkavtsev I, Shioda T, Jain RK. Differential gene expression of primary cultured lymphatic and blood vascular endothelial cells. Neoplasia 2007; 9:1038-45. PubMed
  • Dillon RL, Brown ST, Ling C, Shioda T, Muller WJ. An EGR2/CITED1 transcription factor complex and the 14-3-3sigma tumor suppressor are involved in regulating ErbB2 expression in a transgenic-mouse model of human breast cancer. Mol Cell Biol 2007; 27:8648-57. PubMed
  • Wang Z, Dahiya S, Provencher H, Muir B, Carney E, Coser K, Shioda T, Ma XJ, Sgroi DC. The prognostic biomarkers HOXB13, IL17BR, and CHDH are regulated by estrogen in breast cancer. Clin Cancer Res 2007; 13:6327-34. PubMed
  • McBryan J, Howlin J, Kenny PA, Shioda T, Martin F. ERalpha-CITED1 co-regulated genes expressed during pubertal mammary gland development: implications for breast cancer prognosis. Oncogene 2007; 26:6406-19. PubMed
  • Kashiwagi A, DiGirolamo CM, Kanda Y, Niikura Y, Esmon CT, Hansen TR, Shioda T, Pru JK. The postimplantation embryo differentially regulates endometrial gene expression and decidualization. Endocrinology 2007; 148:4173-84. PubMed
  • Boyle S, Shioda T, Perantoni AO, de Caestecker M. Cited1 and Cited2 are differentially expressed in the developing kidney but are not required for nephrogenesis. Dev Dyn 2007; 236:2321-30. PubMed
  • Yi X, Bouley R, Lin HY, Bechoua S, Sun TX, Del Re E, Shioda T, Raychowdhury MK, Lu HA, Abou-Samra AB, Brown D, Ausiello DA. Alix (AIP1) is a vasopressin receptor (V2R)-interacting protein that increases lysosomal degradation of the V2R. Am J Physiol Renal Physiol 2007; 292:F1303-13. PubMed
  • Yang C, Trent S, Ionescu-Tiba V, Lan L, Shioda T, Sgroi D, Schmidt EV. Identification of cyclin D1- and estrogen-regulated genes contributing to breast carcinogenesis and progression. Cancer Res 2006; 66:11649-58. PubMed
  • Hur J, Bell DW, Dean KL, Coser KR, Hilario PC, Okimoto RA, Tobey EM, Smith SL, Isselbacher KJ, Shioda T. Regulation of expression of BIK proapoptotic protein in human breast cancer cells: p53-dependent induction of BIK mRNA by fulvestrant and proteasomal degradation of BIK protein. Cancer Res 2006; 66:10153-61. PubMed
  • Shioda T, Chesnes J, Coser KR, Zou L, Hur J, Dean KL, Sonnenschein C, Soto AM, Isselbacher KJ. Importance of dosage standardization for interpreting transcriptomal signature profiles: evidence from studies of xenoestrogens. Proc Natl Acad Sci U S A 2006; 103:12033-8. PubMed