Photo of David T Miyamoto,  MD, PhD

David T Miyamoto, MD, PhD

Massachusetts General Hospital

Massachusetts General Hospital
Phone: (617) 726-5866


dmiyamoto@mgh.harvard.edu

David T Miyamoto, MD, PhD

Massachusetts General Hospital

EDUCATIONAL TITLES

  • Assistant Professor, Radiation Oncology, Harvard Medical School
  • Assistant Radiation Oncologist, Radiation Oncology, Massachusetts General Hospital

DF/HCC PROGRAM AFFILIATION

Research Abstract

Circulating tumor cells (CTCs) are rare cancer cells shed from primary and metastatic tumors into the peripheral blood, and represent a “liquid biopsy” that may be performed repeatedly and non-invasively to monitor treatment efficacy and study tumor evolution during therapy. This approach is particularly relevant in metastatic prostate cancer, where the predominance of bone metastases limits the feasibility of tumor sampling using traditional biopsy. In collaboration with the MGH Bio MicroElectroMechanical Systems Resource Center and the MGH Cancer Center, we have developed microfluidic devices to efficiently isolate CTCs from peripheral blood of patients. We have used this novel technology to interrogate androgen receptor signaling status in prostate CTCs, to study the role of CTC clusters in metastasis, and to accomplish single cell RNA-seq of CTCs. Most recently, through comprehensive RNA-seq analysis of prostate CTCs, we demonstrated that activation of noncanonical Wnt signaling may contribute to anti-androgen resistance in prostate cancer. Ongoing research projects include the prospective evaluation of CTC-based biomarkers, the study of the molecular evolution of treatment resistance, and the development of “real-time precision medicine," integrating the genomic analyses of liquid biopsies and tissue biopsies to guide the personalized care of patients with prostate cancer.

Publications

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  • Zheng Y, Miyamoto DT, Wittner BS, Sullivan JP, Aceto N, Jordan NV, Yu M, Karabacak NM, Comaills V, Morris R, Desai R, Desai N, Emmons E, Milner JD, Lee RJ, Wu CL, Sequist LV, Haas W, Ting DT, Toner M, Ramaswamy S, Maheswaran S, Haber DA. Expression of β-globin by cancer cells promotes cell survival during blood-borne dissemination. Nat Commun 2017; 8:14344. PubMed
  • Kalinich M, Bhan I, Kwan TT, Miyamoto DT, Javaid S, LiCausi JA, Milner JD, Hong X, Goyal L, Sil S, Choz M, Ho U, Kapur R, Muzikansky A, Zhang H, Weitz DA, Sequist LV, Ryan DP, Chung RT, Zhu AX, Isselbacher KJ, Ting DT, Toner M, Maheswaran S, Haber DA. An RNA-based signature enables high specificity detection of circulating tumor cells in hepatocellular carcinoma. Proc Natl Acad Sci U S A 2017; 114:1123-1128. PubMed
  • Comaills V, Kabeche L, Morris R, Buisson R, Yu M, Madden MW, LiCausi JA, Boukhali M, Tajima K, Pan S, Aceto N, Sil S, Zheng Y, Sundaresan T, Yae T, Jordan NV, Miyamoto DT, Ting DT, Ramaswamy S, Haas W, Zou L, Haber DA, Maheswaran S. Genomic Instability Is Induced by Persistent Proliferation of Cells Undergoing Epithelial-to-Mesenchymal Transition. Cell Rep 2016; 17:2632-2647. PubMed
  • Hwang WL, Hwang KL, Miyamoto DT. The promise of circulating tumor cells for precision cancer therapy. Biomark Med 2016; 10:1269-1285. PubMed
  • Miyamoto DT, Lee RJ. Cell-free and circulating tumor cell-based biomarkers in men with metastatic prostate cancer: Tools for real-time precision medicine? Urol Oncol 2016; 34:490-501. PubMed
  • Saylor PJ, Lee RJ, Arora KS, Deshpande V, Hu R, Olivier K, Meneely E, Rivera MN, Ting DT, Wu CL, Miyamoto DT. Branched chain RNA in situ hybridization for androgen receptor splice variant AR-V7 as a prognostic biomarker for metastatic castration-sensitive prostate cancer. Clin Cancer Res 2016. PubMed
  • Manuel MM, Cho LP, Catalano PJ, Damato AL, Miyamoto DT, Tempany CM, Schmidt EJ, Viswanathan AN. Outcomes with image-based interstitial brachytherapy for vaginal cancer. Radiother Oncol 2016. PubMed
  • Shaw Bagnall J, Byun S, Miyamoto DT, Kang JH, Maheswaran S, Stott SL, Toner M, Manalis SR. Deformability-based cell selection with downstream immunofluorescence analysis. Integr Biol (Camb) 2016. PubMed
  • Miyamoto DT, Zheng Y, Wittner BS, Lee RJ, Zhu H, Broderick KT, Desai R, Fox DB, Brannigan BW, Trautwein J, Arora KS, Desai N, Dahl DM, Sequist LV, Smith MR, Kapur R, Wu CL, Shioda T, Ramaswamy S, Ting DT, Toner M, Maheswaran S, Haber DA. RNA-Seq of single prostate CTCs implicates noncanonical Wnt signaling in antiandrogen resistance. Science 2015; 349:1351-6. PubMed
  • 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
  • Shaw Bagnall J, Byun S, Begum S, Miyamoto DT, Hecht VC, Maheswaran S, Stott SL, Toner M, Hynes RO, Manalis SR. Deformability of Tumor Cells versus Blood Cells. Sci Rep 2015; 5:18542. PubMed
  • Ting DT, Wittner BS, Ligorio M, Vincent Jordan N, Shah AM, Miyamoto DT, Aceto N, Bersani F, Brannigan BW, Xega K, Ciciliano JC, Zhu H, MacKenzie OC, Trautwein J, Arora KS, Shahid M, Ellis HL, Qu N, Bardeesy N, Rivera MN, Deshpande V, Ferrone CR, Kapur R, Ramaswamy S, Shioda T, Toner M, Maheswaran S, Haber DA. Single-cell RNA sequencing identifies extracellular matrix gene expression by pancreatic circulating tumor cells. Cell Rep 2014; 8:1905-18. PubMed
  • Aceto N, Bardia A, Miyamoto DT, Donaldson MC, Wittner BS, Spencer JA, Yu M, Pely A, Engstrom A, Zhu H, Brannigan BW, Kapur R, Stott SL, Shioda T, Ramaswamy S, Ting DT, Lin CP, Toner M, Haber DA, Maheswaran S. Circulating tumor cell clusters are oligoclonal precursors of breast cancer metastasis. Cell 2014; 158:1110-22. PubMed
  • Miyamoto DT, Sequist LV, Lee RJ. Circulating tumour cells-monitoring treatment response in prostate cancer. Nat Rev Clin Oncol 2014. PubMed
  • Seible DM, Gu X, Hyatt AS, Beard CJ, Choueiri TK, Efstathiou JA, Miyamoto DT, Mitin T, Martin NE, Sweeney CJ, Trinh QD, Beckman JA, Basaria S, Nguyen PL. Weight gain on androgen deprivation therapy: which patients are at highest risk? Urology 2014. PubMed
  • Lee RJ, Saylor PJ, Michaelson MD, Rothenberg SM, Smas ME, Miyamoto DT, Gurski CA, Xie W, Maheswaran S, Haber DA, Goldin JG, Smith MR. A dose-ranging study of cabozantinib in men with castration-resistant prostate cancer and bone metastases. Clin Cancer Res 2013. PubMed
  • Ozkumur E, Shah AM, Ciciliano JC, Emmink BL, Miyamoto DT, Brachtel E, Yu M, Chen PI, Morgan B, Trautwein J, Kimura A, Sengupta S, Stott SL, Karabacak NM, Barber TA, Walsh JR, Smith K, Spuhler PS, Sullivan JP, Lee RJ, Ting DT, Luo X, Shaw AT, Bardia A, Sequist LV, Louis DN, Maheswaran S, Kapur R, Haber DA, Toner M. Inertial focusing for tumor antigen-dependent and -independent sorting of rare circulating tumor cells. Sci Transl Med 2013; 5:179ra47. PubMed
  • Miyamoto DT, Viswanathan AN. Concurrent chemoradiation for vaginal cancer. PLoS ONE 2013; 8:e65048. PubMed
  • Miyamoto DT, Lee RJ, Stott SL, Ting DT, Wittner BS, Ulman M, Smas ME, Lord JB, Brannigan BW, Trautwein J, Bander NH, Wu CL, Sequist LV, Smith MR, Ramaswamy S, Toner M, Maheswaran S, Haber DA. Androgen receptor signaling in circulating tumor cells as a marker of hormonally responsive prostate cancer. 2012; 2:995-1003. PubMed
  • Miyamoto DT, Harris JR. Molecular predictors of local tumor control in early-stage breast cancer. Semin Radiat Oncol 2010; 21:35-42. PubMed
  • Stott SL, Hsu CH, Tsukrov DI, Yu M, Miyamoto DT, Waltman BA, Rothenberg SM, Shah AM, Smas ME, Korir GK, Floyd FP, Gilman AJ, Lord JB, Winokur D, Springer S, Irimia D, Nagrath S, Sequist LV, Lee RJ, Isselbacher KJ, Maheswaran S, Haber DA, Toner M. Isolation of circulating tumor cells using a microvortex-generating herringbone-chip. Proc Natl Acad Sci U S A 2010; 107:18392-7. PubMed
  • Miyamoto DT, Mamon HJ, Ryan DP, Willett CG, Ancukiewicz M, Kobayashi WK, Blaszkowsky L, Castillo CF, Hong TS. Outcomes and Tolerability of Chemoradiation Therapy for Pancreatic Cancer Patients Aged 75 Years or Older. Int J Radiat Oncol Biol Phys 2010; 77:1171-7. PubMed
  • Mak RH, Mamon HJ, Ryan DP, Miyamoto DT, Ancukiewicz M, Kobayashi WK, Willett CG, Choi NC, Blaszkowsky LS, Hong TS. Toxicity and outcomes after chemoradiation for esophageal cancer in patients age 75 or older. 2010; 23:316-23. PubMed
  • Stott SL, Lee RJ, Nagrath S, Yu M, Miyamoto DT, Ulkus L, Inserra EJ, Ulman M, Springer S, Nakamura Z, Moore AL, Tsukrov DI, Kempner ME, Dahl DM, Wu CL, Iafrate AJ, Smith MR, Tompkins RG, Sequist LV, Toner M, Haber DA, Maheswaran S. Isolation and characterization of circulating tumor cells from patients with localized and metastatic prostate cancer. Sci Transl Med 2010; 2:25ra23. PubMed
  • Miyamoto DT, Perlman ZE, Burbank KS, Groen AC, Mitchison TJ. The kinesin Eg5 drives poleward microtubule flux in Xenopus laevis egg extract spindles. J Cell Biol 2004; 167:813-8. PubMed
  • Groen AC, Cameron LA, Coughlin M, Miyamoto DT, Mitchison TJ, Ohi R. XRHAMM functions in ran-dependent microtubule nucleation and pole formation during anastral spindle assembly. Curr Biol 2004; 14:1801-11. PubMed
  • Gupta A, Sanada K, Miyamoto DT, Rovelstad S, Nadarajah B, Pearlman AL, Brunstrom J, Tsai LH. Layering defect in p35 deficiency is linked to improper neuronal-glial interaction in radial migration. Nat Neurosci 2003; 6:1284-91. PubMed
  • Miyamoto DT, Perlman ZE, Mitchison TJ, Shirasu-Hiza M. Dynamics of the mitotic spindle--potential therapeutic targets. Prog Cell Cycle Res 2003; 5:349-60. PubMed
  • Haggarty SJ, Mayer TU, Miyamoto DT, Fathi R, King RW, Mitchison TJ, Schreiber SL. Dissecting cellular processes using small molecules: identification of colchicine-like, taxol-like and other small molecules that perturb mitosis. Chem Biol 2000; 7:275-86. PubMed
  • McDonald, W.H., Ohi, R., Miyamoto, D.T., Mitchison, T.J., and Yates, J.R. 3rd.. Comparison of three directly coupled HPLC MS/MS strategies for identification of proteins from complex mixtures: single-dimensional LC-MS/MS, 2-phase MudPIT, and 3-phase MudPIT. 2002; 219:245-51.
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