Zhenfeng Duan, MD, PhD

Massachusetts General Hospital

Massachusetts General Hospital


zduan@partners.org

Zhenfeng Duan, MD, PhD

Massachusetts General Hospital

EDUCATIONAL TITLES

  • Assistant Professor, Orthopaedic Surgery, Harvard Medical School
  • Assistant Professor , Orthopedic Surgery, Massachusetts General Hospital

DF/HCC PROGRAM AFFILIATION

Research Abstract

The overall objectives of our laboratory are to explore biological mechanisms of tumors arising in bone and other tissues. One of the major focuses of the lab is to elucidate the mechanisms of the development of drug resistance in cancer. Previously, we have found multidrug resistance could be partially reversed by siRNA targeting of ABCB1 (MDR1) or by combination of nanoparticles with chemotherapy drug. Recently, we have identified two small molecules that can overcome drug resistance in vitro. Another significant aim of our research is to define the essential kinases that are responsible for proliferation and survival of human sarcoma cells. In addition, translational research into new treatment options for sarcoma patients has been undertaken.

Publications

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  • Choy E, Flamand Y, Balasubramanian S, Butrynski JE, Harmon DC, George S, Cote GM, Wagner AJ, Morgan JA, Sirisawad M, Mani C, Hornicek FJ, Duan Z, Demetri GD. Phase 1 study of oral abexinostat, a histone deacetylase inhibitor, in combination with doxorubicin in patients with metastatic sarcoma. Cancer 2015; 121:1223-30. PubMed
  • Yang X, Feng Y, Gao Y, Shen J, Choy E, Cote G, Harmon D, Zhang Z, Mankin H, Hornicek FJ, Duan Z. NSC23925 prevents the emergence of multidrug resistance in ovarian cancer in vitro and in vivo. Gynecol Oncol 2015; 137:134-42. PubMed
  • Osaka E, Kelly AD, Spentzos D, Choy E, Yang X, Shen JK, Yang P, Mankin HJ, Hornicek FJ, Duan Z. MicroRNA-155 expression is independently predictive of outcome in chordoma. 2015. PubMed
  • Gao Y, Foster R, Yang X, Feng Y, Shen JK, Mankin HJ, Hornicek FJ, Amiji MM, Duan Z. Up-regulation of CD44 in the development of metastasis, recurrence and drug resistance of ovarian cancer. 2015. PubMed
  • Gao Y, Shen JK, Milane L, Hornicek FJ, Amiji MM, Duan Z. Targeted cancer therapy; nanotechnology approaches for overcoming drug resistance. Curr Med Chem 2015. PubMed
  • Feng Y, Sassi S, Shen JK, Yang X, Gao Y, Osaka E, Zhang J, Yang S, Yang C, Mankin HJ, Hornicek FJ, Duan Z. Targeting CDK11 in osteosarcoma cells using the CRISPR-Cas9 system. J Orthop Res 2015; 33:199-207. PubMed
  • Yang X, Iyer AK, Singh A, Choy E, Hornicek FJ, Amiji MM, Duan Z. MDR1 siRNA loaded hyaluronic acid-based CD44 targeted nanoparticle systems circumvent paclitaxel resistance in ovarian cancer. Sci Rep 2015; 5:8509. PubMed
  • Duan Z, Shen J, Yang X, Yang P, Osaka E, Choy E, Cote G, Harmon D, Zhang Y, Nielsen GP, Spentzos D, Mankin H, Hornicek F. Prognostic significance of miRNA-1 (miR-1) expression in patients with chordoma. J Orthop Res 2014; 32:695-701. PubMed
  • Osaka E, Yang X, Shen JK, Yang P, Feng Y, Mankin HJ, Hornicek FJ, Duan Z. MicroRNA-1 (miR-1) inhibits chordoma cell migration and invasion by targeting slug. J Orthop Res 2014. PubMed
  • Shen JK, Cote GM, Choy E, Yang P, Harmon D, Schwab J, Nielsen GP, Chebib I, Ferrone S, Wang X, Wang Y, Mankin H, Hornicek FJ, Duan Z. Programmed Cell Death Ligand 1 Expression in Osteosarcoma. Cancer Immunol Res 2014. PubMed
  • Cipriani NA, Letovanec I, Hornicek FJ, Mullen JT, Duan Z, Borger DR, Nielsen GP. BRAF mutation in 'sarcomas': a possible method to detect de-differentiated melanomas. Histopathology 2014; 64:639-46. PubMed
  • Iyer AK, Duan Z, Amiji MM. Nanodelivery Systems for Nucleic Acid Therapeutics in Drug Resistant Tumors. Mol Pharm 2014. PubMed
  • Guo S, Lopez-Marquez H, Fan KC, Choy E, Cote G, Harmon D, Nielsen GP, Yang C, Zhang C, Mankin H, Hornicek FJ, Borger DR, Duan Z. Synergistic Effects of Targeted PI3K Signaling Inhibition and Chemotherapy in Liposarcoma. PLoS ONE 2014; 9:e93996. PubMed
  • Jia B, Choy E, Cote G, Harmon D, Ye S, Kan Q, Mankin H, Hornicek F, Duan Z. Cyclin-dependent kinase 11 (CDK11) is crucial in the growth of liposarcoma cells. Cancer Lett 2013; 342:104-12. PubMed
  • Kerr DA, Lopez HU, Deshpande V, Hornicek FJ, Duan Z, Zhang Y, Rosenberg AE, Borger DR, Nielsen GP. Molecular Distinction of Chondrosarcoma From Chondroblastic Osteosarcoma Through IDH1/2 Mutations. Am J Surg Pathol 2013. PubMed
  • Zhang L, Guo S, Schwab JH, Nielsen GP, Choy E, Ye S, Zhang Z, Mankin H, Hornicek FJ, Duan Z. Tissue microarray immunohistochemical detection of brachyury is not a prognostic indicator in chordoma. PLoS ONE 2013; 8:e75851. PubMed
  • Lin M, Zhao Y, Wang S, Liu M, Duan Z, Chen Y, Li F, Xu F, Lu T. Recent advances in synthesis and surface modification of lanthanide-doped upconversion nanoparticles for biomedical applications. Biotechnol Adv 2012; 30:1551-61. PubMed
  • Liu X, Nielsen GP, Rosenberg AE, Waterman PR, Yang W, Choy E, Sassi S, Yang S, Harmon DC, Yang C, Schwab JH, Kobayashi E, Mankin HJ, Xavier R, Weissleder R, Duan Z, Hornicek FJ. Establishment and characterization of a novel chordoma cell line: CH22. J Orthop Res 2012; 30:1666-73. PubMed
  • Kobayashi E, Iyer AK, Hornicek FJ, Amiji MM, Duan Z. Lipid-functionalized Dextran Nanosystems to Overcome Multidrug Resistance in Cancer: A Pilot Study. Clin Orthop Relat Res 2012. PubMed
  • Yang W, Liu X, Choy E, Mankin H, Hornicek FJ, Duan Z. Targeting hedgehog-GLI-2 pathway in osteosarcoma. J Orthop Res 2012. PubMed
  • Duan Z, Zhang J, Choy E, Harmon D, Liu X, Nielsen P, Mankin H, Gray NS, Hornicek FJ. Systematic Kinome shRNA Screening Identifies CDK11 (PITSLRE) Kinase Expression Is Critical for Osteosarcoma Cell Growth and Proliferation. Clin Cancer Res 2012; 18:4580-8. PubMed
  • Duan Z, Li X, Huang H, Yuan W, Zheng SL, Liu X, Zhang Z, Choy E, Harmon D, Mankin H, Hornicek F. Synthesis and Evaluation of (2-(4-Methoxyphenyl)-4-quinolinyl)(2-piperidinyl)methanol (NSC23925) Isomers To Reverse Multidrug Resistance in Cancer. J Med Chem 2012. PubMed
  • Kobayashi E, Hornicek FJ, Duan Z. MicroRNA Involvement in Osteosarcoma. Sarcoma 2012; 2012:359739. PubMed
  • Choy E, Hornicek F, Macconaill L, Harmon D, Tariq Z, Garraway L, Duan Z. High-throughput genotyping in osteosarcoma identifies multiple mutations in phosphoinositide-3-kinase and other oncogenes. Cancer 2011. PubMed
  • Liu X, Choy E, Harmon D, Yang S, Yang C, Mankin H, Hornicek FJ, Duan Z. Inhibition of polo-like kinase 1 leads to the suppression of osteosarcoma cell growth in vitro and in vivo. 2011. PubMed
  • Liu X, Choy E, Hornicek FJ, Yang S, Yang C, Harmon D, Mankin H, Duan Z. ROCK1 as a potential therapeutic target in osteosarcoma. J Orthop Res 2011. PubMed
  • Milane L, Duan Z, Amiji M. Role of hypoxia and glycolysis in the development of multi-drug resistance in human tumor cells and the establishment of an orthotopic multi-drug resistant tumor model in nude mice using hypoxic pre-conditioning. Cancer Cell Int 2011; 11:3. PubMed
  • Guo Y, Nemeth JA, O'Brien C, Susa M, Liu X, Zhang Z, Choy E, Mankin H, Hornicek FJ, Duan Z. Effects of Siltuximab on the IL-6 Induced Signaling Pathway in Ovarian Cancer. Clin Cancer Res 2010; 16:5759-69. PubMed
  • Susa M, Choy E, Liu X, Schwab JH, Hornicek FJ, Mankin H, Duan Z. Cyclin G-associated kinase is necessary for osteosarcoma cell proliferation and receptor trafficking. Mol Cancer Ther 2010; 9:3342-50. PubMed
  • DeLaney TF, Duan Z, Hornicek FJ. Proteomic profiling of chordoma. J Surg Oncol 2010; 102:719. PubMed
  • Milane LJ, Duan Z, Amiji MM. Development of EGFR-Targeted Polymer Blend Nanocarriers for Paclitaxel/Lonidamine Delivery to Treat Multi-Drug Resistance in Human Breast and Ovarian Tumor Cells. Mol Pharm 2010. PubMed
  • Yang C, Hornicek FJ, Wood KB, Schwab JH, Choy E, Mankin H, Duan Z. Blockage of Stat3 With CDDO-Me Inhibits Tumor Cell Growth in Chordoma. Spine 2010; 35:1668-75. PubMed
  • Duan Z, Ji D, Weinstein EJ, Liu X, Susa M, Choy E, Yang C, Mankin H, Hornicek FJ. Lentiviral shRNA screen of human kinases identifies PLK1 as a potential therapeutic target for osteosarcoma. Cancer Lett 2010; 293:220-9. PubMed
  • Ryu K, Choy E, Yang C, Susa M, Hornicek FJ, Mankin H, Duan Z. Activation of signal transducer and activator of transcription 3 (Stat3) pathway in osteosarcoma cells and overexpression of phosphorylated-Stat3 correlates with poor prognosis. J Orthop Res 2010; 28:971-8. PubMed
  • Yang C, Hornicek FJ, Wood KB, Schwab JH, Choy E, Iafrate J, Rosenberg A, Nielsen GP, Xavier RJ, Mankin H, Duan Z. Characterization and analysis of human chordoma cell lines. Spine 2010; 35:1257-64. PubMed
  • van Vlerken LE, Duan Z, Little SR, Seiden MV, Amiji MM. Augmentation of Therapeutic Efficacy in Drug-Resistant Tumor Models Using Ceramide Coadministration in Temporal-Controlled Polymer-Blend Nanoparticle Delivery Systems. 2010; 12:171-80. PubMed
  • Duan Z, Choy E, Nielsen GP, Rosenberg A, Iafrate J, Yang C, Schwab J, Mankin H, Xavier R, Hornicek FJ. Differential expression of microRNA (miRNA) in chordoma reveals a role for miRNA-1 in Met expression. J Orthop Res 2010; 28:746-52. PubMed
  • Susa M, Milane L, Amiji MM, Hornicek FJ, Duan Z. Nanoparticles: A Promising Modality in the Treatment of Sarcomas. 2010. PubMed
  • Yang C, Choy E, Hornicek FJ, Wood KB, Schwab JH, Liu X, Mankin H, Duan Z. Histone deacetylase inhibitor (HDACI) PCI-24781 potentiates cytotoxic effects of doxorubicin in bone sarcoma cells. Cancer Chemother Pharmacol 2010. PubMed
  • Yang C, Ji D, Weinstein EJ, Choy E, Hornicek FJ, Wood KB, Liu X, Mankin H, Duan Z. The Kinase Mirk is a Potential Therapeutic Target in Osteosarcoma. Carcinogenesis 2010; 31:552-8. PubMed
  • Susa M, Choy E, Yang C, Schwab J, Mankin H, Hornicek F, Duan Z. Multidrug resistance reversal agent, NSC77037, identified with a cell-based screening assay. J Biomol Screen 2010; 15:287-96. PubMed
  • Ryu K, Susa M, Choy E, Yang C, Hornicek FJ, Mankin HJ, Duan Z. Oleanane triterpenoid CDDO-Me induces apoptosis in multidrug resistant osteosarcoma cells through inhibition of Stat3 pathway. BMC Cancer 2010; 10:187. PubMed
  • Susa M, Iyer AK, Ryu K, Choy E, Hornicek FJ, Mankin H, Milane L, Amiji MM, Duan Z. Inhibition of ABCB1 (MDR1) expression by an siRNA nanoparticulate delivery system to overcome drug resistance in osteosarcoma. PLoS ONE 2010; 5:e10764. PubMed
  • Yang C, Schwab JH, Schoenfeld AJ, Hornicek FJ, Wood KB, Nielsen GP, Choy E, Mankin H, Duan Z. A novel target for treatment of chordoma: signal transducers and activators of transcription 3. Mol Cancer Ther 2009; 8:2597-605. PubMed
  • Duan Z, Choy E, Harmon D, Yang C, Ryu K, Schwab J, Mankin H, Hornicek FJ. Insulin-like growth factor-I receptor tyrosine kinase inhibitor cyclolignan picropodophyllin inhibits proliferation and induces apoptosis in multidrug resistant osteosarcoma cell lines. Mol Cancer Ther 2009; 8:2122-30. PubMed
  • Schwab J, Antonescu C, Boland P, Healey J, Rosenberg A, Nielsen P, Iafrate J, Delaney T, Yoon S, Choy E, Harmon D, Raskin K, Yang C, Mankin H, Springfield D, Hornicek F, Duan Z. Combination of PI3K/mTOR inhibition demonstrates efficacy in human chordoma. Anticancer Res 2009; 29:1867-71. PubMed
  • Duan Z,Choy E,Jimeno JM,Cuevas Cdel M,Mankin HJ,Hornicek FJ. Diverse cross-resistance phenotype to ET-743 and PM00104 in multi-drug resistant cell lines. Cancer Chemother Pharmacol 2008; 63:1121-9. PubMed
  • Duan Z, Choy E, Harmon D, Yang C, Ryu K, Schwab J, Mankin H, Hornicek FJ. ZNF93 increases resistance to ET-743 (Trabectedin; Yondelis) and PM00104 (Zalypsis) in human cancer cell lines. PLoS ONE 2009; 4:e6967. PubMed
  • Yang C,Yang S,Wood KB,Hornicek FJ,Schwab JH,Fondren G,Mankin H,Duan Z. Multidrug resistant osteosarcoma cell lines exhibit deficiency of GADD45alpha expression. Apoptosis 2008; 14:124-33. PubMed
  • Susa M, Iyer AK, Ryu K, Hornicek FJ, Mankin H, Amiji MM, Duan Z. Doxorubicin loaded Polymeric Nanoparticulate Delivery System to overcome drug resistance in osteosarcoma. BMC Cancer 2009; 9:399. PubMed
  • Duan Z, Choy E, Hornicek FJ. NSC23925, identified in a high-throughput cell-based screen, reverses multidrug resistance. PLoS ONE 2009; 4:e7415. PubMed
  • Miao J,Mu D,Ergel B,Singavarapu R,Duan Z,Powers S,Oliva E,Orsulic S. Hepsin colocalizes with desmosomes and induces progression of ovarian cancer in a mouse model. Int J Cancer 2008; 123:2041-7. PubMed
  • Duan Z,Weinstein EJ,Ji D,Ames RY,Choy E,Mankin H,Hornicek FJ. Lentiviral short hairpin RNA screen of genes associated with multidrug resistance identifies PRP-4 as a new regulator of chemoresistance in human ovarian cancer. Mol Cancer Ther 2008; 7:2377-85. PubMed
  • Devalapally H,Duan Z,Seiden MV,Amiji MM. Modulation of drug resistance in ovarian adenocarcinoma by enhancing intracellular ceramide using tamoxifen-loaded biodegradable polymeric nanoparticles. Clin Cancer Res 2008; 14:3193-203. PubMed
  • Duan Z, Bradner J, Greenberg E, Mazitschek R, Foster R, Mahoney J, Seiden MV. 8-benzyl-4-oxo-8-azabicyclo[3.2.1]oct-2-ene-6,7-dicarboxylic acid (SD-1008), a novel janus kinase 2 inhibitor, increases chemotherapy sensitivity in human ovarian cancer cells. Mol Pharmacol 2007; 72:1137-45. PubMed
  • Devalapally H, Duan Z, Seiden MV, Amiji MM. Paclitaxel and ceramide co-administration in biodegradable polymeric nanoparticulate delivery system to overcome drug resistance in ovarian cancer. Int J Cancer 2007; 121:1830-8. PubMed
  • van Vlerken LE, Duan Z, Seiden MV, Amiji MM. Modulation of intracellular ceramide using polymeric nanoparticles to overcome multidrug resistance in cancer. Cancer Res 2007; 67:4843-50. PubMed
  • Duan Z, Bradner JE, Greenberg E, Levine R, Foster R, Mahoney J, Seiden MV. SD-1029 inhibits signal transducer and activator of transcription 3 nuclear translocation. Clin Cancer Res 2006; 12:6844-52. PubMed
  • Duan Z, Foster R, Bell DA, Mahoney J, Wolak K, Vaidya A, Hampel C, Lee H, Seiden MV. Signal transducers and activators of transcription 3 pathway activation in drug-resistant ovarian cancer. Clin Cancer Res 2006; 12:5055-63. PubMed
  • Duan Z, Foster R, Brakora KA, Yusuf RZ, Seiden MV. GBP1 overexpression is associated with a paclitaxel resistance phenotype. Cancer Chemother Pharmacol 2005; 57:25-33. PubMed
  • Duan Z, Lamendola DE, Duan Y, Yusuf RZ, Seiden MV. Description of paclitaxel resistance-associated genes in ovarian and breast cancer cell lines. Cancer Chemother Pharmacol 2004; 55:277-85. PubMed
  • Duan Z, Duan Y, Lamendola DE, Yusuf RZ, Naeem R, Penson RT, Seiden MV. Overexpression of MAGE/GAGE genes in paclitaxel/doxorubicin-resistant human cancer cell lines. Clin Cancer Res 2003; 9:2778-85. PubMed
  • Lamendola DE, Duan Z, Yusuf RZ, Seiden MV. Molecular description of evolving paclitaxel resistance in the SKOV-3 human ovarian carcinoma cell line. Cancer Res 2003; 63:2200-5. PubMed
  • Duan Z, Feller AJ, Penson RT, Chabner BA, Seiden MV. Discovery of differentially expressed genes associated with paclitaxel resistance using cDNA array technology: analysis of interleukin (IL) 6, IL-8, and monocyte chemotactic protein 1 in the paclitaxel-resistant phenotype. Clin Cancer Res 1999; 5:3445-53. PubMed
  • Duan Z, Feller AJ, Toh HC, Makastorsis T, Seiden MV. TRAG-3, a novel gene, isolated from a taxol-resistant ovarian carcinoma cell line. Gene 1999; 229:75-81. PubMed
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