The Sarcoma and Molecular Biology Lab at MassGeneral Hospital

Sarcoma Molecular Biology Laboratory

The Sarcoma Molecular Biology Laboratory conducts studies on molecular biology of sarcoma and mechanisms of multidrug resistance

Overview

Sarcoma and Molecular Biology Lab at MassGeneral Hospital

The Sarcoma Molecular Biology Laboratory (SMBL), is under the direction of Zhenfeng Duan, MD, PhD and Orthopaedic Oncology Service Chief,Francis J. Hornicek, MD, PhD. The focus of the Laboratory’s work is to study the molecular biology of sarcoma and to examine the mechanisms of multidrug resistance, to identify small molecules and targets to reverse drug resistance and to understand the characterization of molecular mechanisms governing growth, and the proliferation of human sarcoma cells.

The overall objectives of the laboratory are to explore biological mechanisms of tumors arising in bone and other tissues. One of the major focuses 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 and in vivo. Another significant aim of the 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.

The Sarcoma Molecular Biology Laboratory has published articles pertaining to multiple drug resistance in human cancer. Research projects on sarcoma biology have received funding from a variety of sources including NIH, foundations, corporate sponsors, and benefactors.

Group Members

Co-Directors:

Co-Investigators:

Fellows:

  • Li Min
  • Chao Han
  • Xiaoyang Li
  • Jinglu Wang
  • Fan Tang
  • Min Zeng

Research Projects

Current Research Projects:

  • Mechanisms of multidrug resistance in human cancer
  • Overcome multidrug resistance by nanotechnology and small molecular compound
  • Targeting sarcoma with small molecule kinase inhibitors
Sarcoma and Molecular Biology Lab at MassGeneral Hospital; Reverse Drug Resistance by Nanotechnology Sarcoma and Molecular Biology Lab at MassGeneral Hospital; Reverse Drug Resistance by Nanotechnology

Doxorubicin, with stains red, has only partially penetrated these drug resistant osteosarcoma cells. The black cell centers indicate low drug levels in the nuclei.

Nanoparticle-packaged doxorubicin has more completely penetrated these drug resistant osteosarcoma cells. The red centers indicate more effective drug uptake.

Publications

  1. 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 Feb;33(2):199-207.
  2. Yang X, Iyer AK, Singh A, Milane L, Choy E, Hornicek FJ, Amiji MM, Duan Z. Cluster of Differentiation 44 Targeted Hyaluronic Acid Based Nanoparticles for MDR1 siRNA Delivery to Overcome Drug Resistance in Ovarian Cancer. Pharm Res. 2014 Dec 17
  3. 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 Apr 15;121(8):1223-30
  4. Shen JK, Cote GM, Choy E, Hornicek FJ, Duan Z. Targeting programmed cell death ligand 1 in osteosarcoma: an auto-commentary on therapeutic potential. Oncoimmunology. 2014 Aug 3;3(8):e954467.
  5. 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 Apr;137(1):134-42.
  6. 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 Feb 17;5:8509.
  7. 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. Oncotarget. 2015 Mar 13.
  8. 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. Oncotarget. 2015 Mar 16
  9. Feng Y, Shen J, Gao Y, Liao Y, Cote G, Choy E, Chebib I, Mankin H, Hornicek F, Duan Z. Expression of programmed cell death ligand 1 (PD-L1) and prevalence of tumor-infiltrating lymphocytes (TILs) in chordoma. Oncotarget. 2015 May 10;6(13):11139-49.
  10. Yang X, Shen J, Gao Y, Feng Y, Guan Y, Zhang Z, Mankin H, Hornicek FJ, Duan Z. NSC23925 prevents the development of paclitaxel resistance by inhibiting the introduction of P-glycoprotein (Pgp) and enhancing apoptosis. Int J Cancer. 2015 Oct 15;137(8):2029-39
  11. Zhang L, Lyer AK, Yang X, Kobayashi E, Guo Y, Mankin H, Hornicek FJ, Amiji MM, Duan Z. Polymeric nanoparticle-based delivery of microRNA-199a-3p inhibits proliferation and growth of osteosarcoma cells. Int J Nanomedicine. 2015 Apr 15;10:2913-24
  12. Gao Y, Feng Y, Shen JK, Lin M, Choy E, Cote GM, Harmon DC, Mankin HJ, Hornicek FJ, Duan Z. CD44 is a direct target of miR-199a-3p and contributes to aggressive progression in osteosarcoma. Sci Rep. 2015 Jun 16;5:11365.
  13. Ye S, Zhang J, Shen J, Gao Y, Li Y, Choy E, Cote G, Harmon D, Mankin H, Gray NS, Hornicek FJ, Duan Z. NVP-TAE684 reverses multidrug resistance (MDR) in human osteosarcoma by inhibiting P-glycoprotein (PGP1) function. Br J Pharmacol. 2016 Feb;173(3):613-26.
  14. Liao Y, Feng Y, Shen J, Gao Y, Cote G, Choy E, Harmon D, Mankin H, Hornicek F, Duan Z. Clinical and biological significance of PIM1 kinase in osteosarcoma. J Orthop Res. 2015 Dec 19. doi: 10.1002/jor.23134.
  15. Ye S, Shen J, Choy E, Yang C, Mankin H, Hornicek F, Duan Z. p53 overexpression increases chemosensitivity in multidrug-resistant osteosarcoma cell lines. Cancer Chemother Pharmacol. 2016 Feb;77(2):349-56.
  16. Gao Y, Liao Y, Shen JK, Feng Y, Choy E, Cote G, Harmon D, Mankin HJ, Hornicek FJ, Duan Z. Evaluation of P-glycoprotein (Pgp) expression in human osteosarcoma by high-throughput tissue microarray. J Orthop Res. 2016 Jan 21. doi: 10.1002/jor.23173.
  17. Shen JK, Cote GM, Gao Y, Choy E, Mankin HJ, Hornicek FJ, Duan Z. Targeting EZH2-mediated methylation of H3K27 inhibits proliferation and migration of Synovial Sarcoma in vitro. Sci Rep. 2016 Apr 29;6:25239
  18. Gao Y, Shen JK, Choy E, Zhang Z, Mankin HJ, Hornicek FJ, Duan Z. Pharmacokinetics and tolerability of NSC23925b, a novel P-glycoprotein inhibitor: preclinical study in mice and rats. Sci Rep. 2016 May 9;6:25659.
  19. Sun R, Shen J, Gao Y, Zhou Y, Yu Z, Hornicek F, Kan Q, Duan Z. Sun R, Shen J, Gao Y, Zhou Y, Yu Z, Hornicek F, Kan Q, Duan Z. verexpression of EZH2 is associated with the poor prognosis in osteosarcoma and function analysis indicates a therapeutic potential. Oncotarget. 2016 May 20. doi: 10.18632/oncotarget.9518.
  20. Liu X, Gao Y, Shen J, Yang W, Choy E, Mankin H, Hornicek FJ, Duan Z. Cyclin-dependent Kinase 11 (CDK11) is Required for Ovarian Cancer Cell Growth in vitro and in vivo, and its Inhibition Causes Apoptosis and Sensitizes Cells to Paclitaxel. Mol Cancer Ther. 2016 May 20. pii: molcanther.0032.2016.
  21. 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;22(11):1335-47.
  22. Sun X, Guo W, Shen JK, Mankin HJ, Hornicek FJ, Duan Z. Rhabdomyosarcoma: Advances in Molecular and Cellular Biology. Sarcoma. 2015;2015:232010
  23. Lin M, Gao Y, Hornicek F, Xu F, Lu TJ, Amiji M, Duan Z. Near-infrared light activated delivery platform for cancer therapy. Adv Colloid Interface Sci. 2015 Dec;226(Pt B):123-37
  24. Sun R, Shen JK, Choy E, Yu Z, Hornicek FJ, Duan Z. The emerging roles and therapeutic potential of microRNAs (miRs) in liposarcoma. Discov Med. 2015 Nov;20(111):311-24.
  25. Liao Y, Feng Y, Shen J, Hornicek FJ, Duan Z. The roles and therapeutic potential of cyclin-dependent kinases (CDKs) in sarcoma. Cancer Metastasis Rev. 2016 Jun;35(2):151-63.
  26. Liu T, Shen JK, Li Z, Choy E, Hornicek FJ, Duan Z. Development and potential applications of CRISPR-Cas9 genome editing technology in sarcoma. Cancer Lett. 2016 Apr 1;373(1):109-18.
  27. Chen H, Shen J, Choy E, Hornicek FJ, Duan Z. Targeting protein kinases to reverse multidrug resistance in sarcoma. Cancer Treat Rev. 2016 Feb;43:8-18.
  28. Zhou Y, Shen JK, Hornicek FJ, Kan Q, Duan Z. The emerging roles and therapeutic potential of cyclin-dependent kinase 11 (CDK11) in human cancer. Oncotarget. 2016 Mar 31. doi: 10.18632/oncotarget.8519.
  29. Li J, Shen J, Wang K, Hornicek F, Duan Z. The Roles of Sox Family Genes in Sarcoma. Curr Drug Targets. 2016 May 2.
  30. Min L, Shen J, Tu C, Hornicek F, Duan Z. The roles and implications of exosomes in sarcoma. Cancer Metastasis Rev. 2016.

Contact

Contact Us

Sarcoma Molecular Biology Laboratory

55 Fruit Street, GRJ-11-1106 Boston, MA 02114
  • Phone: 617-724-3144

Dr. Francis Hornicek, Chief, MGH Orthopaedic Oncology Service

Francis Hornicek, MD, PhD
Chief, Orthopaedic Oncology Service
email: fhornicek@partners.org

Zhenfeng Duan, MD, PhD

Zhenfeng Duan, MD, PhD
email: zduan@partners.org

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