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Last Name
Institution

Gavin Yong Wang

Title
InstitutionMedical University of South Carolina
DepartmentPathology and Laboratory Medicine
AddressP.O. Box MSC 908
RS401
39 Sabin Street
Phone843-792-9983
Fax843-792-4157
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    Collapse Overview 
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    Oxidative stress is a state of reduction and oxidation (redox) imbalance caused by increased reactive oxygen species (ROS) generation, decreased antioxidant capacity, or both. Thus, it is important for cells to maintain a state of redox homeostasis by regulating the equilibrium between ROS production and scavenging capacity. Cancer cells are often exposed to intrinsic and extrinsic stresses that produce high levels of ROS and DNA damage. More importantly, we and others have shown that induction of oxidative stress is one of the underlying mechanisms of action for many anticancer drugs and radiation. Growing evidence has revealed that cancer stem cells (CSCs) play a critical role in therapy resistance and tumor relapse, as demonstrated by the fact that CSCs are selectively enriched in residual tumors following anticancer therapies. However, there is still an important gap in our knowledge of the mechanisms whereby CSCs maintain redox balance and counteract ionizing radiation (IR) and ROS-generating drug-induced oxidative stress. Our preliminary studies have demonstrated that CSCs are less responsive to IR and cisplatin-induced cell killing than non-stem cancer cells (NSCs) of human triple-negative breast cancer (TNBC). Moreover, we have found that ROS levels are significantly lower in CSCs than NSCs. These results suggest that CSCs have the capacity to maintain low levels of ROS and thus evade oxidative stress-induced toxicity. On the basis of these findings, we hypothesize that CSCs adopt a distinct redox signaling system to counteract oxidative stress and maintain lower levels of ROS, which consequently confers therapy-resistance to CSCs by overriding oxidative stress-induced cell death. Therefore, targeting of selective redox signaling pathways should sensitize therapy-resistant CSCs to ROS-generating anticancer drugs and radiotherapy. Three specific Aims are proposed to test this hypothesis: Aim 1 will define differences in redox signaling pathways between CSCs and NSCs; Aim 2 will elucidate the mechanisms whereby CSCs maintain lower levels of ROS and self-renewal capacity; and Aim 3 will determine if targeting of selective redox signaling pathways sensitizes therapy-resistant CSCs to chemotherapy and radiation. We anticipate the outcomes of this project will provide novel insights into the mechanisms whereby CSCs evade anticancer therapy-induced oxidative stress. New information obtained from this project will be essential to the development of innovative therapeutic strategies to eliminate therapy-resistant CSCs in human cancers and thus improve the efficacy of cancer treatment.

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    Stem Cell Biology, MicroRNAs in Lung Cancer, Development of Novel Sensitizers for Lung Cancer Radiotherapy

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    Collapse selected publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
    List All   |   Timeline
    1. Bartolini D, Tew KD, Marinelli R, Galli F, Wang GY. Nrf2-modulation by seleno-hormetic agents and its potential for radiation protection. Biofactors. 2019 Oct 16. PMID: 31617634.
      View in: PubMed
    2. Zhang L, Zhang J, Ye Z, Manevich Y, Ball LE, Bethard JR, Jiang YL, Broome AM, Dalton AC, Wang GY, Townsend DM, Tew KD. Isoflavone ME-344 Disrupts Redox Homeostasis and Mitochondrial Function by Targeting Heme Oxygenase 1. Cancer Res. 2019 Aug 15; 79(16):4072-4085. PMID: 31227482.
      View in: PubMed
    3. Zhong G, Qin S, Townsend D, Schulte BA, Tew KD, Wang GY. Oxidative stress induces senescence in breast cancer stem cells. Biochem Biophys Res Commun. 2019 Jul 05; 514(4):1204-1209. PMID: 31109646.
      View in: PubMed
    4. Wang Y, Zeng J, Wu W, Xie S, Yu H, Li G, Zhu T, Li F, Lu J, Wang GY, Xie X, Zhang J. Nicotinamide N-methyltransferase enhances chemoresistance in breast cancer through SIRT1 protein stabilization. Breast Cancer Res. 2019 05 17; 21(1):64. PMID: 31101119.
      View in: PubMed
    5. Bartolini D, Wang Y, Zhang J, Giustarini D, Rossi R, Wang GY, Torquato P, Townsend DM, Tew KD, Galli F. A seleno-hormetine protects bone marrow hematopoietic cells against ionizing radiation-induced toxicities. PLoS One. 2019; 14(4):e0205626. PMID: 31034521.
      View in: PubMed
    6. Qin S, Schulte BA, Wang GY. Role of senescence induction in cancer treatment. World J Clin Oncol. 2018 Dec 20; 9(8):180-187. PMID: 30622926.
      View in: PubMed
    7. Klauber-DeMore N, Schulte BA, Wang GY. Targeting MYC for triple-negative breast cancer treatment. Oncoscience. 2018 May; 5(5-6):120-121. PMID: 30035158.
      View in: PubMed
    8. Yang A, Qin S, Schulte BA, Ethier SP, Tew KD, Wang GY. MYC Inhibition Depletes Cancer Stem-like Cells in Triple-Negative Breast Cancer. Cancer Res. 2017 12 01; 77(23):6641-6650. PMID: 28951456.
      View in: PubMed
    9. He X, Yang A, McDonald DG, Riemer EC, Vanek KN, Schulte BA, Wang GY. MiR-34a modulates ionizing radiation-induced senescence in lung cancer cells. Oncotarget. 2017 Sep 19; 8(41):69797-69807. PMID: 29050242.
      View in: PubMed
    10. Yang A, Xiao X, Zhao M, LaRue AC, Schulte BA, Wang GY. Differential Reponses of Hematopoietic Stem and Progenitor Cells to mTOR Inhibition. Stem Cells Int. 2015; 2015:561404. PMID: 26221145.
      View in: PubMed
    11. Xiao X, Luo H, Vanek KN, LaRue AC, Schulte BA, Wang GY. Catalase inhibits ionizing radiation-induced apoptosis in hematopoietic stem and progenitor cells. Stem Cells Dev. 2015 Jun 01; 24(11):1342-51. PMID: 25603016.
      View in: PubMed
    12. Shao L, Feng W, Li H, Gardner D, Luo Y, Wang Y, Liu L, Meng A, Sharpless NE, Zhou D. Total body irradiation causes long-term mouse BM injury via induction of HSC premature senescence in an Ink4a- and Arf-independent manner. Blood. 2014 May 15; 123(20):3105-15. PMID: 24622326.
      View in: PubMed
    13. Luo H, Wang L, Schulte BA, Yang A, Tang S, Wang GY. Resveratrol enhances ionizing radiation-induced premature senescence in lung cancer cells. Int J Oncol. 2013 Dec; 43(6):1999-2006. PMID: 24141489.
      View in: PubMed
    14. An N, Lin YW, Mahajan S, Kellner JN, Wang Y, Li Z, Kraft AS, Kang Y. Pim1 serine/threonine kinase regulates the number and functions of murine hematopoietic stem cells. Stem Cells. 2013 Jun; 31(6):1202-12. PMID: 23495171.
      View in: PubMed
    15. Luo H, Yount C, Lang H, Yang A, Riemer EC, Lyons K, Vanek KN, Silvestri GA, Schulte BA, Wang GY. Activation of p53 with Nutlin-3a radiosensitizes lung cancer cells via enhancing radiation-induced premature senescence. Lung Cancer. 2013 Aug; 81(2):167-73. PMID: 23683497.
      View in: PubMed
    16. Luo H, Yang A, Schulte BA, Wargovich MJ, Wang GY. Resveratrol induces premature senescence in lung cancer cells via ROS-mediated DNA damage. PLoS One. 2013; 8(3):e60065. PMID: 23533664.
      View in: PubMed
    17. Burns TA, Subathra M, Signorelli P, Choi Y, Yang X, Wang Y, Villani M, Bhalla K, Zhou D, Luberto C. Sphingomyelin synthase 1 activity is regulated by the BCR-ABL oncogene. J Lipid Res. 2013 Mar; 54(3):794-805. PMID: 23160178.
      View in: PubMed
    18. Diaz-Montero CM, Wang Y, Shao L, Feng W, Zidan AA, Pazoles CJ, Montero AJ, Zhou D. The glutathione disulfide mimetic NOV-002 inhibits cyclophosphamide-induced hematopoietic and immune suppression by reducing oxidative stress. Free Radic Biol Med. 2012 May 01; 52(9):1560-8. PMID: 22343421.
      View in: PubMed
    19. Zou J, Zou P, Wang J, Li L, Wang Y, Zhou D, Liu L. Inhibition of p38 MAPK activity promotes ex vivo expansion of human cord blood hematopoietic stem cells. Ann Hematol. 2012 Jun; 91(6):813-23. PMID: 22258328.
      View in: PubMed
    20. Wang Y, Liu L, Zhou D. Inhibition of p38 MAPK attenuates ionizing radiation-induced hematopoietic cell senescence and residual bone marrow injury. Radiat Res. 2011 Dec; 176(6):743-52. PMID: 22014293.
      View in: PubMed
    21. Li D, Wang Y, Wu H, Lu L, Zhang H, Chang J, Zhai Z, Zhang J, Wang Y, Zhou D, Meng A. Mitigation of ionizing radiation-induced bone marrow suppression by p38 inhibition and G-CSF administration. J Radiat Res. 2011; 52(6):712-6. PMID: 21971035.
      View in: PubMed
    22. Shao L, Li H, Pazhanisamy SK, Meng A, Wang Y, Zhou D. Reactive oxygen species and hematopoietic stem cell senescence. Int J Hematol. 2011 Jul; 94(1):24-32. PMID: 21567162.
      View in: PubMed
    23. Li H, Wang Y, Pazhanisamy SK, Shao L, Batinic-Haberle I, Meng A, Zhou D. Mn(III) meso-tetrakis-(N-ethylpyridinium-2-yl) porphyrin mitigates total body irradiation-induced long-term bone marrow suppression. Free Radic Biol Med. 2011 Jul 01; 51(1):30-7. PMID: 21565268.
      View in: PubMed
    24. Pazhanisamy SK, Li H, Wang Y, Batinic-Haberle I, Zhou D. NADPH oxidase inhibition attenuates total body irradiation-induced haematopoietic genomic instability. Mutagenesis. 2011 May; 26(3):431-5. PMID: 21415439.
      View in: PubMed
    25. Wang Y, Kellner J, Liu L, Zhou D. Inhibition of p38 mitogen-activated protein kinase promotes ex vivo hematopoietic stem cell expansion. Stem Cells Dev. 2011 Jul; 20(7):1143-52. PMID: 21198398.
      View in: PubMed
    26. Wang Y, Scheiber MN, Neumann C, Calin GA, Zhou D. MicroRNA regulation of ionizing radiation-induced premature senescence. Int J Radiat Oncol Biol Phys. 2011 Nov 01; 81(3):839-48. PMID: 21093163.
      View in: PubMed
    27. Johnson SM, Torrice CD, Bell JF, Monahan KB, Jiang Q, Wang Y, Ramsey MR, Jin J, Wong KK, Su L, Zhou D, Sharpless NE. Mitigation of hematologic radiation toxicity in mice through pharmacological quiescence induced by CDK4/6 inhibition. J Clin Invest. 2010 Jul; 120(7):2528-36. PMID: 20577054.
      View in: PubMed
    28. Wang Y, Liu L, Pazhanisamy SK, Li H, Meng A, Zhou D. Total body irradiation causes residual bone marrow injury by induction of persistent oxidative stress in murine hematopoietic stem cells. Free Radic Biol Med. 2010 Jan 15; 48(2):348-56. PMID: 19925862.
      View in: PubMed
    29. Foster K, Wang Y, Zhou D, Wright C. Dependence on PI3K/Akt signaling for malignant rhabdoid tumor cell survival. Cancer Chemother Pharmacol. 2009 Apr; 63(5):783-91. PMID: 18641990.
      View in: PubMed
    30. Probin V, Wang Y, Zhou D. Busulfan-induced senescence is dependent on ROS production upstream of the MAPK pathway. Free Radic Biol Med. 2007 Jun 15; 42(12):1858-65. PMID: 17512465.
      View in: PubMed
    31. Probin V, Wang Y, Bai A, Zhou D. Busulfan selectively induces cellular senescence but not apoptosis in WI38 fibroblasts via a p53-independent but extracellular signal-regulated kinase-p38 mitogen-activated protein kinase-dependent mechanism. J Pharmacol Exp Ther. 2006 Nov; 319(2):551-60. PMID: 16882877.
      View in: PubMed
    32. Wang Y, Probin V, Zhou D. Cancer therapy-induced residual bone marrow injury-Mechanisms of induction and implication for therapy. Curr Cancer Ther Rev. 2006 Aug 01; 2(3):271-279. PMID: 19936034.
      View in: PubMed
    33. Wang Y, Schulte BA, Zhou D. Hematopoietic stem cell senescence and long-term bone marrow injury. Cell Cycle. 2006 Jan; 5(1):35-8. PMID: 16319536.
      View in: PubMed
    34. Wang Y, Schulte BA, LaRue AC, Ogawa M, Zhou D. Total body irradiation selectively induces murine hematopoietic stem cell senescence. Blood. 2006 Jan 01; 107(1):358-66. PMID: 16150936.
      View in: PubMed
    35. Wang Y, Meng A, Lang H, Brown SA, Konopa JL, Kindy MS, Schmiedt RA, Thompson JS, Zhou D. Activation of nuclear factor kappaB In vivo selectively protects the murine small intestine against ionizing radiation-induced damage. Cancer Res. 2004 Sep 01; 64(17):6240-6. PMID: 15342410.
      View in: PubMed
    36. Wang Y, Meng A, Zhou D. Inhibition of phosphatidylinostol 3-kinase uncouples H2O2-induced senescent phenotype and cell cycle arrest in normal human diploid fibroblasts. Exp Cell Res. 2004 Aug 01; 298(1):188-96. PMID: 15242773.
      View in: PubMed
    37. Bai A, Meier GP, Wang Y, Luberto C, Hannun YA, Zhou D. Prodrug modification increases potassium tricyclo[5.2.1.0(2,6)]-decan-8-yl dithiocarbonate (D609) chemical stability and cytotoxicity against U937 leukemia cells. J Pharmacol Exp Ther. 2004 Jun; 309(3):1051-9. PMID: 14960662.
      View in: PubMed
    38. Meng A, Wang Y, Brown SA, Van Zant G, Zhou D. Ionizing radiation and busulfan inhibit murine bone marrow cell hematopoietic function via apoptosis-dependent and -independent mechanisms. Exp Hematol. 2003 Dec; 31(12):1348-56. PMID: 14662344.
      View in: PubMed
    39. Meng A, Yu T, Chen G, Brown SA, Wang Y, Thompson JS, Zhou D. Cellular origin of ionizing radiation-induced NF-kappaB activation in vivo and role of NF-kappaB in ionizing radiation-induced lymphocyte apoptosis. Int J Radiat Biol. 2003 Nov; 79(11):849-61. PMID: 14698954.
      View in: PubMed
    40. Meng A, Wang Y, Van Zant G, Zhou D. Ionizing radiation and busulfan induce premature senescence in murine bone marrow hematopoietic cells. Cancer Res. 2003 Sep 01; 63(17):5414-9. PMID: 14500376.
      View in: PubMed
    41. Zhang B, Wang Y, Zheng GG, Ma XT, Li G, Zhang FK, Wu KF. Clinical significance of IL-18 gene over-expression in AML. Leuk Res. 2002 Oct; 26(10):887-92. PMID: 12163048.
      View in: PubMed
    42. Wang Y, Zheng GG, Wu KF, Li G, Rao Q. Construction of macrophage colony-stimulating factor receptor DNA vaccine. Haematologica. 2001 Nov; 86(11):1219-20. PMID: 11694409.
      View in: PubMed
    43. Wang Y, Li G, Zheng GG, Song YH, Wu KF. Detection and sequencing analysis of IL-18 expression in J(6-1_ leukemic cells. Leuk Res. 2001 Mar; 25(3):273-4. PMID: 11261420.
      View in: PubMed
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