Xinping Zhang
| Title | Associate Professor |
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| Institution | School of Medicine and Dentistry |
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| Department | Orthopaedics in the Center for Musculoskeletal Research |
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| Address | University of Rochester Medical Center
School of Medicine and Dentistry
601 Elmwood Ave, Box 665
Rochester NY 14642
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| 2002 |
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| Orthopaedic Research Society Travel Fellowship Award | | 2005 |
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| Orthopaedic Research Society New Investigator Recognition Award | | 2008 |
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| MTF J.R. Neff Award |
Dr. Zhang's research centers on finding ways to "revitalize, " or reactivate the healing processes of bone. When people suffer massive bone loss due to traumatic injury or a tumor, bone grafts are used to restore the shape and strength of the bone. Even when a bone graft from the patient's own body is used, healing and strengthening are sometimes never complete.
By studying how our body's cells mature to become bone-forming cells, Dr. Zhang hopes to find ways to turn the process of healing on so that the entire bone graft will heal after surgery.
Adult mesenchymal stem cells (MSCs) have enormous potential for bone tissue repair and regeneration. Our research has been focused on understanding the molecular and cellular mechanisms that control the activation, proliferation and differentiation of mesenchymal stem cells during skeletal repair. We are particularly interested in the periosteal stem cells that play key roles in repair and regeneration. Our current program has integrated the following topics:
1) Molecular signals that control mesenchymal stem cell differentiation.
2) Mechanism of skeletal repair and regeneration
3) Stem cell therapy and bone tissue engineering for repair and reconstruction of large segmental defects.
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Yazici C, Takahata M, Reynolds DG, Xie C, Samulski RJ, Samulski J, Beecham EJ, Gertzman AA, Spilker M, Zhang X, O'Keefe RJ, Awad HA, Schwarz EM. Self-complementary AAV2.5-BMP2-coated femoral allografts mediated superior bone healing versus live autografts in mice with equivalent biomechanics to unfractured femur. Mol Ther. 2011 Aug; 19(8):1416-25.
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Wang Q, Huang C, Xue M, Zhang X. Expression of endogenous BMP-2 in periosteal progenitor cells is essential for bone healing. Bone. 2011 Mar 1; 48(3):524-32.
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Wang Q, Huang C, Zeng F, Xue M, Zhang X. Activation of the Hh pathway in periosteum-derived mesenchymal stem cells induces bone formation in vivo: implication for postnatal bone repair. Am J Pathol. 2010 Dec; 177(6):3100-11.
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Liu Y, Zhang X, Xia Y, Yang H. Magnetic-field-assisted electrospinning of aligned straight and wavy polymeric nanofibers. Adv Mater. 2010 Jun 11; 22(22):2454-7.
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Tsutsumi R, Xie C, Wei X, Zhang M, Zhang X, Flick LM, Schwarz EM, O'Keefe RJ. PGE2 signaling through the EP4 receptor on fibroblasts upregulates RANKL and stimulates osteolysis. J Bone Miner Res. 2009 Oct; 24(10):1753-62.
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Xie C, Liang B, Xue M, Lin AS, Loiselle A, Schwarz EM, Guldberg RE, O'Keefe RJ, Zhang X. Rescue of impaired fracture healing in COX-2-/- mice via activation of prostaglandin E2 receptor subtype 4. Am J Pathol. 2009 Aug; 175(2):772-85.
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Wei X, Zhang X, Flick LM, Drissi H, Schwarz EM, O'Keefe RJ. Titanium particles stimulate COX-2 expression in synovial fibroblasts through an oxidative stress-induced, calpain-dependent, NF-kappaB pathway. Am J Physiol Cell Physiol. 2009 Aug; 297(2):C310-20.
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Clark CA, Li TF, Kim KO, Drissi H, Zuscik MJ, Zhang X, O'Keefe RJ. Prostaglandin E2 inhibits BMP signaling and delays chondrocyte maturation. J Orthop Res. 2009 Jun; 27(6):785-92.
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Naik AA, Xie C, Zuscik MJ, Kingsley P, Schwarz EM, Awad H, Guldberg R, Drissi H, Puzas JE, Boyce B, Zhang X, O'Keefe RJ. Reduced COX-2 expression in aged mice is associated with impaired fracture healing. J Bone Miner Res. 2009 Feb; 24(2):251-64.
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Xie C, Ming X, Wang Q, Schwarz EM, Guldberg RE, O'Keefe RJ, Zhang X. COX-2 from the injury milieu is critical for the initiation of periosteal progenitor cell mediated bone healing. Bone. 2008 Dec; 43(6):1075-83.
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Yazici C, Yanoso L, Xie C, Reynolds DG, Samulski RJ, Samulski J, Yannariello-Brown J, Gertzman AA, Zhang X, Awad HA, Schwarz EM. The effect of surface demineralization of cortical bone allograft on the properties of recombinant adeno-associated virus coatings. Biomaterials. 2008 Oct; 29(28):3882-7.
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Zhang X, Awad HA, O'Keefe RJ, Guldberg RE, Schwarz EM. A perspective: engineering periosteum for structural bone graft healing. Clin Orthop Relat Res. 2008 Aug; 466(8):1777-87.
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Xie C, Xue M, Wang Q, Schwarz EM, O'Keefe RJ, Zhang X. Tamoxifen-inducible CreER-mediated gene targeting in periosteum via bone-graft transplantation. J Bone Joint Surg Am. 2008 Feb; 90 Suppl 1:9-13.
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Zuscik MJ, Hilton MJ, Zhang X, Chen D, O'Keefe RJ. Regulation of chondrogenesis and chondrocyte differentiation by stress. J Clin Invest. 2008 Feb; 118(2):429-38.
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Zhang X, Sun B. Organic crystal fibers aligned into oriented bundles with polarized emission. J Phys Chem B. 2007 Sep 20; 111(37):10881-5.
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Awad HA, Zhang X, Reynolds DG, Guldberg RE, O'Keefe RJ, Schwarz EM. Recent advances in gene delivery for structural bone allografts. Tissue Eng. 2007 Aug; 13(8):1973-85.
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Bärnighausen T, Liu Y, Zhang X, Sauerborn R. Willingness to pay for social health insurance among informal sector workers in Wuhan, China: a contingent valuation study. BMC Health Serv Res. 2007; 7:114.
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Reynolds DG, Hock C, Shaikh S, Jacobson J, Zhang X, Rubery PT, Beck CA, O'keefe RJ, Lerner AL, Schwarz EM, Awad HA. Micro-computed tomography prediction of biomechanical strength in murine structural bone grafts. J Biomech. 2007; 40(14):3178-86.
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Xie C, Reynolds D, Awad H, Rubery PT, Pelled G, Gazit D, Guldberg RE, Schwarz EM, O'Keefe RJ, Zhang X. Structural bone allograft combined with genetically engineered mesenchymal stem cells as a novel platform for bone tissue engineering. Tissue Eng. 2007 Mar; 13(3):435-45.
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Wang Q, Wei X, Zhu T, Zhang M, Shen R, Xing L, O'Keefe RJ, Chen D. Bone morphogenetic protein 2 activates Smad6 gene transcription through bone-specific transcription factor Runx2. J Biol Chem. 2007 Apr 6; 282(14):10742-8.
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Chen M, Lichtler AC, Sheu TJ, Xie C, Zhang X, O'Keefe RJ, Chen D. Generation of a transgenic mouse model with chondrocyte-specific and tamoxifen-inducible expression of Cre recombinase. Genesis. 2007 Jan; 45(1):44-50.
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Zhang X, Sun B, Friend RH, Guo H, Nau D, Giessen H. Metallic photonic crystals based on solution-processible gold nanoparticles. Nano Lett. 2006 Apr; 6(4):651-5.
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O'Keefe RJ, Tiyapatanaputi P, Xie C, Li TF, Clark C, Zuscik MJ, Chen D, Drissi H, Schwarz E, Zhang X. COX-2 has a critical role during incorporation of structural bone allografts. Ann N Y Acad Sci. 2006 Apr; 1068:532-42.
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Murugan R, Ramakrishna S. Nano-featured scaffolds for tissue engineering: a review of spinning methodologies. Tissue Eng. 2006 Mar; 12(3):435-47.
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Zhang X, Naik A, Xie C, Reynolds D, Palmer J, Lin A, Awad H, Guldberg R, Schwarz E, O'Keefe R. Periosteal stem cells are essential for bone revitalization and repair. J Musculoskelet Neuronal Interact. 2005 Oct-Dec; 5(4):360-2.
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Zhang X, Xie C, Lin AS, Ito H, Awad H, Lieberman JR, Rubery PT, Schwarz EM, O'Keefe RJ, Guldberg RE. Periosteal progenitor cell fate in segmental cortical bone graft transplantations: implications for functional tissue engineering. J Bone Miner Res. 2005 Dec; 20(12):2124-37.
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Koefoed M, Ito H, Gromov K, Reynolds DG, Awad HA, Rubery PT, Ulrich-Vinther M, Soballe K, Guldberg RE, Lin AS, O'Keefe RJ, Zhang X, Schwarz EM. Biological effects of rAAV-caAlk2 coating on structural allograft healing. Mol Ther. 2005 Aug; 12(2):212-8.
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Carmouche JJ, Puzas JE, Zhang X, Tiyapatanaputi P, Cory-Slechta DA, Gelein R, Zuscik M, Rosier RN, Boyce BF, O'Keefe RJ, Schwarz EM. Lead exposure inhibits fracture healing and is associated with increased chondrogenesis, delay in cartilage mineralization, and a decrease in osteoprogenitor frequency. Environ Health Perspect. 2005 Jun; 113(6):749-55.
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Clark CA, Schwarz EM, Zhang X, Ziran NM, Drissi H, O'Keefe RJ, Zuscik MJ. Differential regulation of EP receptor isoforms during chondrogenesis and chondrocyte maturation. Biochem Biophys Res Commun. 2005 Mar 18; 328(3):764-76.
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Wei X, Zhang X, Zuscik MJ, Drissi MH, Schwarz EM, O'Keefe RJ. Fibroblasts express RANKL and support osteoclastogenesis in a COX-2-dependent manner after stimulation with titanium particles. J Bone Miner Res. 2005 Jul; 20(7):1136-48.
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Ito H, Koefoed M, Tiyapatanaputi P, Gromov K, Goater JJ, Carmouche J, Zhang X, Rubery PT, Rabinowitz J, Samulski RJ, Nakamura T, Soballe K, O'Keefe RJ, Boyce BF, Schwarz EM. Remodeling of cortical bone allografts mediated by adherent rAAV-RANKL and VEGF gene therapy. Nat Med. 2005 Mar; 11(3):291-7.
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Gu X, Feng Y, Shi C, Li M, Fu Z, Zhang X. Antiapoptotic mechanism of insulin in reoxygenation-induced injury in cultured cardiomyocytes of neonatal rats. J Huazhong Univ Sci Technolog Med Sci. 2005; 25(6):632-5.
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Guldberg RE, Oest M, Lin AS, Ito H, Chao X, Gromov K, Goater JJ, Koefoed M, Schwarz EM, O'Keefe RJ, Zhang X. Functional integration of tissue-engineered bone constructs. J Musculoskelet Neuronal Interact. 2004 Dec; 4(4):399-400.
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Tiyapatanaputi P, Rubery PT, Carmouche J, Schwarz EM, O'keefe RJ, Zhang X. A novel murine segmental femoral graft model. J Orthop Res. 2004 Nov; 22(6):1254-60.
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Li TF, Zuscik MJ, Ionescu AM, Zhang X, Rosier RN, Schwarz EM, Drissi H, O'Keefe RJ. PGE2 inhibits chondrocyte differentiation through PKA and PKC signaling. Exp Cell Res. 2004 Oct 15; 300(1):159-69.
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Zhang X, Ziran N, Goater JJ, Schwarz EM, Puzas JE, Rosier RN, Zuscik M, Drissi H, O'Keefe RJ. Primary murine limb bud mesenchymal cells in long-term culture complete chondrocyte differentiation: TGF-beta delays hypertrophy and PGE2 inhibits terminal differentiation. Bone. 2004 May; 34(5):809-17.
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Bukata SV, Gelinas J, Wei X, Rosier RN, Puzas JE, Zhang X, Schwarz EM, Song XY, Griswold DE, O'Keefe RJ. PGE2 and IL-6 production by fibroblasts in response to titanium wear debris particles is mediated through a Cox-2 dependent pathway. J Orthop Res. 2004 Jan; 22(1):6-12.
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Li X, Ionescu AM, Schwarz EM, Zhang X, Drissi H, Puzas JE, Rosier RN, Zuscik MJ, O'Keefe RJ. Smad6 is induced by BMP-2 and modulates chondrocyte differentiation. J Orthop Res. 2003 Sep; 21(5):908-13.
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Flick LM, Weaver JM, Ulrich-Vinther M, Abuzzahab F, Zhang X, Dougall WC, Anderson D, O'Keefe RJ, Schwarz EM. Effects of receptor activator of NFkappaB (RANK) signaling blockade on fracture healing. J Orthop Res. 2003 Jul; 21(4):676-84.
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Zhang X, Schwarz EM, Young DA, Puzas JE, Rosier RN, O'Keefe RJ. Cyclooxygenase-2 regulates mesenchymal cell differentiation into the osteoblast lineage and is critically involved in bone repair. J Clin Invest. 2002 Jun; 109(11):1405-15.
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Mungo DV, Zhang X, O'Keefe RJ, Rosier RN, Puzas JE, Schwarz EM. COX-1 and COX-2 expression in osteoid osteomas. J Orthop Res. 2002 Jan; 20(1):159-62.
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Zhang X, Morham SG, Langenbach R, Baggs RB, Young DA. Lack of cyclooxygenase-2 inhibits growth of teratocarcinomas in mice. Exp Cell Res. 2000 Feb 1; 254(2):232-40.
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Zhang X, Morham SG, Langenbach R, Young DA. Malignant transformation and antineoplastic actions of nonsteroidal antiinflammatory drugs (NSAIDs) on cyclooxygenase-null embryo fibroblasts. J Exp Med. 1999 Aug 16; 190(4):451-59.
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