Photo of Bruce R. Zetter,  PhD

Bruce R. Zetter, PhD

Boston Children's Hospital

Boston Children's Hospital
Phone: (617) 919-2320
Fax: (617) 730-0268

Bruce R. Zetter, PhD

Boston Children's Hospital


  • Charles Nowiszewski Professor of Cancer Biology, Surgery, Harvard Medical School


Research Abstract

Our research is focused on the changes in gene and protein expression that take place as tumors progress from highly differentiated, non-aggressive lesions to poorly differentiated, metastatic tumors. The phenotype required for metastasis includes decreased cell aggregation, increased angiogenesis, increased cell migration and increased tissue degradation. The goal of our laboratory is to identify these molecules, to determine the mechanism by which their expression is altered in tumor progression and to employ them for both diagnostic and therapeutic purposes.

Using proteomics tools, we have identified a variety of proteins altered in tumor progression in breast, pancreas, prostate, bladder and other tumor sites. Our model systems include tumor cell lines that differ in their metastatic potential, as well as transgenic animal models in which tumors arise spontaneously in the prostate or pancreas at distinct times after birth. Using this approach, we have developed tests for biomarkers that are useful in cancer diagnosis, prognosis, recurrence monitoring and in determining responsiveness to particular therapeutic agents.

We have recently focused on the development of resistance to taxanes. Taxanes such as paclitaxel and docetaxel are now front-line treatment for patients with a variety of metastatic cancers, yet their efficacy is diminished by the rapid development of drug resistance. We have found that the protein Prohibitin1 is upregulated on the surface of taxane-resistant cells. We believe that Prohibitin1 can be used as a biomarker to reveal which patients have tumors that will be resistant to taxane treatment. In addition, cell surface Prohibitin1 could serve as a target to direct other drugs to taxane-resistant tumor cells.

Because metastasis is the end point for most human cancers and because metastatic lesions are so often resistant to conventional therapies, we have initiated a drug screen to identify new therapies that act preferentially on metastatic tumors. We have identified several candidate therapies that we now wish to move rapidly to clinical trial.

Publications from Harvard Catalyst Profiles

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  • Islam MA, Rice J, Reesor E, Zope H, Tao W, Lim M, Ding J, Chen Y, Aduluso D, Zetter BR, Farokhzad OC, Shi J. Adjuvant-pulsed mRNA vaccine nanoparticle for immunoprophylactic and therapeutic tumor suppression in mice. Biomaterials 2021; 266:120431. PubMed
  • Chung I, Zhou K, Barrows C, Banyard J, Wilson A, Rummel N, Mizokami A, Basu S, Sengupta P, Shaikh B, Sengupta S, Bielenberg DR, Zetter BR. Unbiased Phenotype-Based Screen Identifies Therapeutic Agents Selective for Metastatic Prostate Cancer. 2020; 10:594141. PubMed
  • Wang J, Zope H, Islam MA, Rice J, Dodman S, Lipert K, Chen Y, Zetter BR, Shi J. Lipidation Approaches Potentiate Adjuvant-Pulsed Immune Surveillance: A Design Rationale for Cancer Nanovaccine. Front Bioeng Biotechnol 2020; 8:787. PubMed
  • Ghalali A, Rice JM, Kusztos A, Jernigan FE, Zetter BR, Rogers MS. Developing a novel FRET assay, targeting the binding between Antizyme-AZIN. Sci Rep 2019; 9:4632. PubMed
  • Islam MA, Xu Y, Tao W, Ubellacker JM, Lim M, Aum D, Lee GY, Zhou K, Zope H, Yu M, Cao W, Oswald JT, Dinarvand M, Mahmoudi M, Langer R, Kantoff PW, Farokhzad OC, Zetter BR, Shi J. Restoration of tumour-growth suppression in vivo via systemic nanoparticle-mediated delivery of PTEN mRNA. Nat Biomed Eng 2018; 2:850-864. PubMed
  • Cheong JE, Zaffagni M, Chung I, Xu Y, Wang Y, Jernigan FE, Zetter BR, Sun L. Synthesis and anticancer activity of novel water soluble benzimidazole carbamates. Eur J Med Chem 2017; 144:372-385. PubMed
  • Xu Y, Yang W, Shi J, Zetter BR. Prohibitin 1 regulates tumor cell apoptosis via the interaction with X-linked inhibitor of apoptosis protein. 2016. PubMed
  • Islam MA, Reesor EK, Xu Y, Zope HR, Zetter BR, Shi J. Biomaterials for mRNA delivery. Biomater Sci 2015. PubMed
  • Zhu X, Xu Y, Solis LM, Tao W, Wang L, Behrens C, Xu X, Zhao L, Liu D, Wu J, Zhang N, Wistuba II, Farokhzad OC, Zetter BR, Shi J. Long-circulating siRNA nanoparticles for validating Prohibitin1-targeted non-small cell lung cancer treatment. Proc Natl Acad Sci U S A 2015; 112:7779-84. PubMed
  • Shi J, Xu Y, Xu X, Zhu X, Pridgen E, Wu J, Votruba AR, Swami A, Zetter BR, Farokhzad OC. Hybrid lipid-polymer nanoparticles for sustained siRNA delivery and gene silencing. 2014. PubMed
  • Banyard J, Chung I, Migliozzi M, Phan DT, Wilson AM, Zetter BR, Bielenberg DR. Identification of genes regulating migration and invasion using a new model of metastatic prostate cancer. BMC Cancer 2014; 14:387. PubMed
  • Zhang Y, Yan W, Collins MA, Bednar F, Rakshit S, Zetter BR, Stanger BZ, Chung I, Rhim AD, di Magliano MP. Interleukin-6 is required for pancreatic cancer progression by promoting MAPK signaling activation and oxidative stress resistance. Cancer Res 2013; 73:6359-74. PubMed
  • Coughlin MF, Bielenberg DR, Lenormand G, Marinkovic M, Waghorne CG, Zetter BR, Fredberg JJ. Cytoskeletal stiffness, friction, and fluidity of cancer cell lines with different metastatic potential. Clin Exp Metastasis 2013. PubMed
  • Banyard J, Chung I, Wilson AM, Vetter G, Le Béchec A, Bielenberg DR, Zetter BR. Regulation of epithelial plasticity by miR-424 and miR-200 in a new prostate cancer metastasis model. Sci Rep 2013; 3:3151. PubMed
  • Freeman KW, Bowman BR, Zetter BR. Regenerative protein thymosin beta-4 is a novel regulator of purinergic signaling. FASEB J 2011; 25:907-15. PubMed
  • Yang W, Cai Q, Lui VW, Everley PA, Kim J, Bhola N, Quesnelle KM, Zetter BR, Steen H, Freeman MR, Grandis JR. Quantitative Proteomics Analysis Reveals Molecular Networks Regulated by Epidermal Growth Factor Receptor Level in Head and Neck Cancer. J Proteome Res 2010; 9:3073-82. PubMed
  • Spivey KA, Banyard J, Solis LM, Wistuba II, Barletta JA, Gandhi L, Feldman HA, Rodig SJ, Chirieac LR, Zetter BR. Collagen XXIII: a potential biomarker for the detection of primary and recurrent non-small cell lung cancer. Cancer Epidemiol Biomarkers Prev 2010; 19:1362-72. PubMed
  • Mu CJ, Lavan DA, Langer RS, Zetter BR. Self-Assembled Gold Nanoparticle Molecular Probes for Detecting Proteolytic Activity In Vivo. ACS Nano 2010; 4:1511-20. PubMed
  • Patel N, Chatterjee SK, Vrbanac V, Chung I, Mu CJ, Olsen RR, Waghorne C, Zetter BR. Rescue of paclitaxel sensitivity by repression of Prohibitin1 in drug-resistant cancer cells. Proc Natl Acad Sci U S A 2010; 107:2503-8. PubMed
  • Banyard J,Barrows C,Zetter BR. Differential regulation of human thymosin beta 15 isoforms by transforming growth factor beta 1. Genes Chromosomes Cancer 2009; 48:502-9. PubMed
  • Feldman AS,Banyard J,Wu CL,McDougal WS,Zetter BR. Cystatin B as a tissue and urinary biomarker of bladder cancer recurrence and disease progression. Clin Cancer Res 2009; 15:1024-31. PubMed
  • Zetter BR. The scientific contributions of M. Judah Folkman to cancer research. Nat Rev Cancer 2008; 8:647-54. PubMed
  • Arap W, Trepel M, Zetter BR, Pasqualini R. Meeting report: innovations in prostate cancer research. Cancer Res 2008; 68:635-8. PubMed
  • Mangold U, Hayakawa H, Coughlin M, Münger K, Zetter BR. Antizyme, a mediator of ubiquitin-independent proteasomal degradation and its inhibitor localize to centrosomes and modulate centriole amplification. Oncogene 2008; 27:604-13. PubMed
  • Banyard J, Bao L, Hofer MD, Zurakowski D, Spivey KA, Feldman AS, Hutchinson LM, Kuefer R, Rubin MA, Zetter BR. Collagen XXIII Expression Is Associated with Prostate Cancer Recurrence and Distant Metastases. Clin Cancer Res 2007; 13:2634-42. PubMed
  • Everley PA, Bakalarski CE, Elias JE, Waghorne CG, Beausoleil SA, Gerber SA, Faherty BK, Zetter BR, Gygi SP. Enhanced analysis of metastatic prostate cancer using stable isotopes and high mass accuracy instrumentation. J Proteome Res 2006; 5:1224-31. PubMed
  • Chatterjee SK, Zetter BR. Cancer biomarkers: knowing the present and predicting the future. Future Oncol 2005; 1:37-50. PubMed
  • Connor Y, Tekleab S, Nandakumar S, Walls C, Tekleab Y, Husain A, Gadish O, Sabbisetti V, Kaushik S, Sehrawat S, Kulkarni A, Dvorak H, Zetter B, R Edelman E, Sengupta S. Physical nanoscale conduit-mediated communication between tumour cells and the endothelium modulates endothelial phenotype. Nat Commun ; 6:8671. PubMed
  • Bielenberg DR, Zetter BR. The Contribution of Angiogenesis to the Process of Metastasis. Cancer J ; 21:267-73. PubMed
  • Mangold U, Hayakawa H, Coughlin M, Münger K, Zetter BR. Antizyme, a mediator of ubiquitin-independent proteasomal degradation and its inhibitor localize to centrosomes and modulate centriole amplification. Oncogene ; 27:604-13.