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]


Powered by Harvard Catalyst
  • 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
  • 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
  • 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
  • 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
  • Plisov S, Tsang M, Shi G, Boyle S, Yoshino K, Dunwoodie SL, Dawid IB, Shioda T, Perantoni AO, de Caestecker MP. Cited1 is a bifunctional transcriptional cofactor that regulates early nephronic patterning. J Am Soc Nephrol 2005; 16:1632-44. PubMed
  • Hur J, Chesnes J, Coser KR, Lee RS, Geck P, Isselbacher KJ, Shioda T. The Bik BH3-only protein is induced in estrogen-starved and antiestrogen-exposed breast cancer cells and provokes apoptosis. Proc Natl Acad Sci U S A 2004; 101:2351-6. PubMed
  • Shioda T. Application of DNA microarray to toxicological research. J Environ Pathol Toxicol Oncol 2004; 23:13-31. PubMed
  • Rodriguez TA, Sparrow DB, Scott AN, Withington SL, Preis JI, Michalicek J, Clements M, Tsang TE, Shioda T, Beddington RS, Dunwoodie SL. Cited1 is required in trophoblasts for placental development and for embryo growth and survival. Mol Cell Biol 2003; 24:228-44. PubMed
  • Coser KR, Chesnes J, Hur J, Ray S, Isselbacher KJ, Shioda T. Global analysis of ligand sensitivity of estrogen inducible and suppressible genes in MCF7/BUS breast cancer cells by DNA microarray. Proc Natl Acad Sci U S A 2003; 100:13994-9. PubMed
  • Yahata T, Takedatsu H, Dunwoodie SL, Bragan. Cloning of mouse Cited4, a member of the CITED family p300/CBP-binding transcriptional coactivators: induced expression in mammary epithelial cells. Genomics 2002; 80:601-13. PubMed
  • Bragan. Human CREB-binding protein/p300-interacting transactivator with ED-rich tail (CITED) 4, a new member of the CITED family, functions as a co-activator for transcription factor AP-2. J Biol Chem 2001; 277:8559-65. PubMed
  • Yahata T, Shao W, Endoh H, Hur J, Coser KR, Sun H, Ueda Y, Kato S, Isselbacher KJ, Brown M, Shioda T. Selective coactivation of estrogen-dependent transcription by CITED1 CBP/p300-binding protein. Genes Dev 2001; 15:2598-612. PubMed
  • Nair SS, Chaubal VA, Shioda T, Coser KR, Mojamdar M. Over-expression of MSG1 transcriptional co-activator increases melanin in B16 melanoma cells: a possible role for MSG1 in melanogenesis. Pigment Cell Res 2001; 14:206-9. PubMed
  • Sado T, Fenner MH, Tan SS, Tam P, Shioda T, Li E. X inactivation in the mouse embryo deficient for Dnmt1: distinct effect of hypomethylation on imprinted and random X inactivation. Dev Biol 2000; 225:294-303. PubMed
  • Yahata T, Andriole S, Isselbacher KJ, Shioda T. Estimation of baculovirus titer by beta-galactosidase activity assay of virus preparations. Biotechniques 2000; 29:214-5. PubMed
  • Andrews JE, O'Neill MJ, Binder M, Shioda T, Sinclair AH. Isolation and expression of a novel member of the CITED family. Mech Dev 2000; 95:305-8. PubMed
  • Shioda T, Andriole S, Yahata T, Isselbacher KJ. A green fluorescent protein-reporter mammalian two-hybrid system with extrachromosomal maintenance of a prey expression plasmid: application to interaction screening. Proc Natl Acad Sci U S A 2000; 97:5220-4. PubMed
  • Yahata T, de Caestecker MP, Lechleider RJ, Andriole S, Roberts AB, Isselbacher KJ, Shioda T. The MSG1 non-DNA-binding transactivator binds to the p300/CBP coactivators, enhancing their functional link to the Smad transcription factors. J Biol Chem 2000; 275:8825-34. PubMed
  • de Caestecker MP, Yahata T, Wang D, Parks WT, Huang S, Hill CS, Shioda T, Roberts AB, Lechleider RJ. The Smad4 activation domain (SAD) is a proline-rich, p300-dependent transcriptional activation domain. J Biol Chem 2000; 275:2115-22. PubMed
  • Shioda T, Lechleider RJ, Dunwoodie SL, Li H, Yahata T, de Caestecker MP, Fenner MH, Roberts AB, Isselbacher KJ. Transcriptional activating activity of Smad4: roles of SMAD hetero-oligomerization and enhancement by an associating transactivator. Proc Natl Acad Sci U S A 1998; 95:9785-90. PubMed
  • Fenner MH, Parrish JE, Boyd Y, Reed V, MacDonald M, Nelson DL, Isselbacher KJ, Shioda T. MSG1 (melanocyte-specific gene 1): mapping to chromosome Xq13.1, genomic organization, and promoter analysis. Genomics 1998; 51:401-7. PubMed
  • Li H, Ahmed NU, Fenner MH, Ueda M, Isselbacher KJ, Shioda T. Regulation of expression of MSG1 melanocyte-specific nuclear protein in human melanocytes and melanoma cells. Exp Cell Res 1998; 242:478-86. PubMed
  • Shioda T, Fenner MH, Isselbacher KJ. MSG1 and its related protein MRG1 share a transcription activating domain. Gene 1998; 204:235-41. PubMed
  • Shiraki K, Tsuji N, Shioda T, Isselbacher KJ, Takahashi H. Expression of Fas ligand in liver metastases of human colonic adenocarcinomas. Proc Natl Acad Sci U S A 1997; 94:6420-5. PubMed
  • Shioda T, Munn LL, Fenner MH, Jain RK, Isselbacher KJ. Early events of metastasis in the microcirculation involve changes in gene expression of cancer cells. Tracking mRNA levels of metastasizing cancer cells in the chick embryo chorioallantoic membrane. Am J Pathol 1997; 150:2099-112. PubMed
  • Shioda T, Fenner MH, Isselbacher KJ. Experimental animal model of hematogenous cardiac metastasis and neoplastic cardiac tamponade. J Surg Oncol 1997; 64:122-6. PubMed
  • Shioda T, Fenner MH, Isselbacher KJ. msg1, a novel melanocyte-specific gene, encodes a nuclear protein and is associated with pigmentation. Proc Natl Acad Sci U S A 1996; 93:12298-303. PubMed
  • Shioda T, Ohta T, Isselbacher KJ, Rhoads DB. Differentiation-dependent expression of the Na+/glucose cotransporter (SGLT1) in LLC-PK1 cells: role of protein kinase C activation and ongoing transcription. Proc Natl Acad Sci U S A 1994; 91:11919-23. PubMed
  • Itoh H, Shioda T, Matsura T, Koyama S, Nakanishi T, Kajiyama G, Kawasaki T. Iron ion induces mitochondrial DNA damage in HTC rat hepatoma cell culture--role of antioxidants in mitochondrial DNA protection from oxidative stresses. Arch Biochem Biophys 1994; 313:120-5. PubMed
  • Egi Y, Koyama S, Shioda T, Yamada K, Kawasaki T. Identification, purification and reconstitution of thiamin metabolizing enzymes in human red blood cells. Biochim Biophys Acta 1992; 1160:171-8. PubMed
  • Shioda T, Kawasaki T. Thiamin triphosphate does not affect contraction of skinned fibers. J Nutr Sci Vitaminol (Tokyo) 1992; 38:529-33. PubMed
  • Shioda T, Egi Y, Yamada K, Yamada M, Nakazawa A, Kawasaki T. Synthesis and accumulation of thiamin triphosphate in Escherichia coli cells expressing chicken cytosolic adenylate kinase. Biochim Biophys Acta 1991; 1115:36-41. PubMed
  • Shioda T, Egi Y, Yamada K, Kawasaki T. Properties of thiamin triphosphate-synthesizing activity of chicken cytosolic adenylate kinase and the effect of adenine nucleotides. Biochim Biophys Acta 1991; 1115:30-5. PubMed
  • Miyoshi K, Egi Y, Shioda T, Kawasaki T. Evidence for in vivo synthesis of thiamin triphosphate by cytosolic adenylate kinase in chicken skeletal muscle. J Biochem (Tokyo) 1990; 108:267-70. PubMed