We have found that treatment of many types of cancer cell with oncolytic virus causes apoptosis, but some cancers can acquire resistance. We are seeking to understand this resistance so that strategies to avoid or reverse it may be developed. We are also investigating genomic evolution in cancer and in model bacteria as an indicator of disrupted regulatory pathways.
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Thirukkumaran CM, Nodwell MJ, Hirasawa K, Shi ZQ, Diaz R, Luider J, Johnston RN, Forsyth PA, Magliocco AM, Lee P, Nishikawa S, Donnelly B, Coffey M, Trpkov K, Fonseca K, Spurrell J, Morris DG. (2010) Oncolytic Viral Therapy for Prostate Cancer: Efficacy of Reovirus as a Biological Therapeutic. Cancer Research 70: 2435-44.
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Cho IR, Koh SS, Min HJ, Park EH, Srisuttee R, Jhun BH, Kang CD, Kim M, Johnston RN, Chung YH. (2010) Reovirus infection induces apoptosis of TRAIL-resistant gastric cancer cells by down-regulation of Akt activation. Int J Oncol 36:1023-30.
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Kim M, Hansen K, Davis L, van Marle G, Gill J, Fox J, Hollenberg M, Rancourt D, Lee P, Johnston RN. (2010) Z-FA-FMK as a novel potent inhibitor of reovirus pathogenesis and oncolysis in vivo. Antiviral Therapy (in press).
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Chen F, Liu WQ, Peng YH, Zou QH, Wang Y, Li YG, Zhou J, Zhu DL, Eisenstark A, Johnston RN, Liu GR, Liu SL. (2010) Experimental conversion of mutL alleles and its effects on genome diversification: implications in regulation of bacterial mutability in evolution. PloS One (in press).
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Park EH, Park EH, Cho IR, Srisuttee R, Min HJ, Oh MJ, Jeong YJ, Jhun BH, Johnston RN, Lee S, Koh SS, Chung YH. (2010) CUG2, a novel oncogene confers reoviral replication through Ras and p38 signaling pathway. Cancer Gene Therapy 17:307-14.
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Kim M, Williamson CT, Prudhomme J, Bebb DG, Riabowol K, Lee PWK, Lees-Miller SP, Mori Y, Rahman MM, McFadden G, Johnston RN. (2010) The viral tropism of two distinct oncolytic viruses, reovirus and myxoma virus, is modulated by cellular tumor suppressor gene status. Oncogene (in press).
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Cho IR, Koh SS, Min HJ, Park EH, Ratakorn S, Jhun BH, Jeong SH, Yoo YH, Youn HD, Johnston RN, Chung YH (2010) Down-regulation of HIF-1a by oncolytic reovirus infection is independent of VHL and p53. Cancer Gene Therapy 17:365-72.
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Liu WQ, Feng Y, Wang Y, Zou QH, Chen F, Guo JT, Peng YH, Jin Y, Li YG, Hu SN, Johnston RN, Liu GR, Liu SL. (2009) Salmonella paratyphi C: genetic divergence from Salmonella choleraesuis and pathogenic convergence with Salmonella typhi. PLoS ONE 4: 1-8.
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Chen F, Poppe, C, Liu GR, Li YG, Peng YH, Sanderson K, Johnston RN, Liu SL. (2009) A genome map of Salmonella agona: numerous insertions and deletions reflecting the evolutionary history of a human pathogen. FEMS Microbio Lett 293: 188-95.
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Pai RB, Pai SB, Lalitha RM, Kumaraswamy SV, Lalitha N, Johnston RN, Bhargava MK. (2009) Overexpression of c-Myc oncoprotein in oral squamous cell carcinoma in the south Indian population. eCancer 3: 1-7 (DOI: 10.3332/ecancer.2008.128).
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Min HJ, Koh SS, Cho IR, Srisuttee R, Park EH, Jhun BH, Kim YJ, Oh ST, Kwak JE, Johnston RN, Chung YH (2009). Inhibition of GSK-3ß enhances reovirus-induced apoptosis in colon cancer cells. Int J Oncol 35: 617-24.
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Cho IR, Koh SS, Min HJ, Park EH, Ratakorn S, Jhun BH, Jeong SH, Yoo YH, Youn HD, Johnston RN, Chung YH (2009) Down-regulation of HIF-1a by oncolytic reovirus infection is independent of VHL and p53. Cancer Gene Therapy (accepted with revision).
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Kim M, Williamson C, Bebb G, Riabowol K, Lee PWK, Lees-Miller S, McFadden G, Johnston RN. The viral tropism of two distinct oncolytic viruses, reovirus and myxoma virus, is determined by cellular tumor suppressor gene functionality. Oncogene (accepted with revision).
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Min HJ, Cho IR, Ratakorn S, Park EH, Cho DH, Ahn JH, Lee IS, Johnston RN, Oh S, Chung YH. (2008). Hexachlorophene suppresses β-catenin expression by up-regulation of Siah-1 in EBV-infected B lymphoma cells. Cancer Letters 276: 136-142.
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Park EH, Koh SS, Srisuttee R, Cho IR, Min HJ, Jhun BH, Lee YS, Jang KL, Kim CH, Johnston RN, Chung YH. (2008) Expression of HBX, an oncoprotein of hepatitis B virus, blocks reoviral oncolysis of hepatocellular carcinoma cells. Cancer Gene Therapy 16:453-461.
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Liu WQ, Feng Y, Wang Y, Zou QH, Chen F, Guo JT, Peng YH, Jin Y, Li YG, Hu SN, Johnston RN, Liu GR, Liu SL. (2009) Salmonella paratyphi C: genetic divergence from Salmonella choleraesuis and pathogenic convergence with Salmonella typhi. PLoS ONE 4: 1-8.
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Kim M, Egan C, Alain T, Urbanski S, Lee PWK, Forsyth PA, Johnston RN. (2007) Acquired resistance to reoviral oncolysis in Ras-transformed fibrosarcoma cells. Oncogene 26: 4124-34.
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Alain T, Wong JF, Urbanski SJ, Lee PW, Muruve DA, Johnston RN, Forsyth PA, Beck PL. (2007) Reovirus decreases azoxymethane-induced aberrant crypt foci and colon cancer in a rodent model. Cancer Gene Therapy 14:867-72.
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Gong J, Liu W-Q, Liu G-R, Chen F, Li J-Q, Xu G-M, Wang L, Johnston RN, Eisenstark A, Liu S-L. (2007) Spontaneous conversion between mutL and 6 bp D mutL in Salmonella typhimurium LT7: association with genome diversification and possible roles in bacterial adaptation. Genomics 90:542-9.
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Kim M, Chung YH, Johnston RN. (2007) Reovirus and tumor oncolysis. J Microbiol 45:187-92.
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Johnston RN, Kim M. (2007) Oncolytic reovirus: susceptibility and resistance in cancer cells. In: Proc Microbiol Soc Korea pp. 46-8.
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Liu WQ, Liu GR, Li JQ, Xu GM, Qi D, He XY, Deng J, Zhang FM, Johnston RN, Liu SL. (2007) Diverse genome structures of Salmonella paratyphi C. BMC Genomics 8:290-99.