Grant McFadden, PhD

Where You Are:
Grant McFadden, PhD

Office  (352) 273-6852

Education And Training
  • PhD, McGill University, 1975 - Biochemistry


The McFadden lab studies the nature of how viruses interact with the host immune system, in particular the mechanisms that determine the host tropism of poxviruses. The lab is also developing specific poxviruses as novel virotherapy candidates for the oncolytic treatment of human cancers. The lab has investigated the molecular basis for the host and cellular tropism specificity of poxviruses, using the myxoma virus model system as a novel platform for replication-restricted vaccine vectors and as an oncolytic virus. His lab also studies how viruses in general can occasionally leap from a long-term evolutionary host species to cause zoonotic infections in humans. He is currently collaborating with U Florida researchers (Drs. Chris Cogle, Ed Scott and Gerard Madlambayan) to develop a novel strategy of using myxoma virus to selectively purge human leukemia/lymphoma cancer cells from patient bone marrow samples ex vivo, prior to engraftment, as an adjunct treatment for autologous blood and marrow transplantation (ABMT). Our lab is also investigating whether myxoma virus can selectively infect and kill primary human cancer stem cells but leave normal human stem cells untouched.

 

 

  • Zemp FJ, McKenzie BA, Lun X, Reilly KM, McFadden G, Yong VW, Forsyth PA. Cellular factors promoting resistance to effective treatment of glioma with oncolytic myxoma virus. Cancer Res. 2014 Dec;74(24):7260-7273. Pubmedid: 25336188.
  • Liu J, McFadden G. SAMD9 is an innate antiviral host factor with stress response properties that can be antagonized by poxviruses. J Virol. 2014 Nov. Pubmedid: 25428864.
  • Ildefonso CJ, Jaime H, Rahman MM, Li Q, Boye SE, Hauswirth WW, Lucas AR, McFadden G, Lewin AS. GENE DELIVERY OF A VIRAL ANTI-INFLAMMATORY PROTEIN TO COMBAT OCULAR INFLAMMATION. Hum Gene Ther. 2014 Nov. Pubmedid: 25420215.
  • Lamb SA, Rahman MM, McFadden G. Recombinant myxoma virus lacking all poxvirus ankyrin-repeat proteins stimulates multiple cellular anti-viral pathways and exhibits a severe decrease in virulence. Virology. 2014 Sep;464-465C:134-145. Pubmedid: 25068401.
  • Lemos de Matos A, Liu J, McFadden G, Esteves PJ. Evolution and divergence of the mammalian SAMD9/SAMD9L gene family. BMC Evol Biol. 2014 Jun;13:121. Pubmedid: 23758988. Pmcid: PMC3685527.
  • Damon IK, Damaso CR, McFadden G. Are we there yet? The smallpox research agenda using variola virus. PLoS Pathog. 2014 May;10(5):e1004108. Pubmedid: 24789223.
  • Weng M, Wei G, Ma M, Chu B, Qin Y, Zhang M, Lun X, McFadden G, Forsyth P, Yang Y, Quan Z. Targeting gallbladder cancer: oncolytic virotherapy with myxoma virus is enhanced by rapamycin in vitro and further improved by hyaluronan in vivo. Mol Cancer. 2014 Apr;13(1):82. Pubmedid: 24725816.
  • Bell J, McFadden G. Viruses for Tumor Therapy. Cell Host Microbe. 2014 Mar;15(3):260-265. Pubmedid: 24629333.
  • Rahman MM, Liu J, Chan WM, Rothenburg S, McFadden G. Myxoma virus protein M029 is a dual function immunomodulator that inhibits PKR and also conscripts RHA/DHX9 to promote expanded host tropism and viral replication. PLoS Pathog. 2014 Feb;9(7):e1003465. Pubmedid: 23853588. Pmcid: PMC3701710.
  • Ogbomo H, Zemp FJ, Lun X, Zhang J, Stack D, Rahman MM, McFadden G, Mody CH, Forsyth PA. Myxoma virus infection promotes NK lysis of malignant gliomas in vitro and in vivo. PLoS One. 2014 Feb;8(6):e66825. Pubmedid: 23762498. Pmcid: PMC3677932.
  • Lemos de Matos A, McFadden G, Esteves PJ. Evolution of viral sensing RIG-I-like receptor genes in Leporidae genera Oryctolagus, Sylvilagus, and Lepus. Immunogenetics. 2014 Jan;66(1):43-52. Pubmedid: 24220721.
  • Haller SL, Peng C, McFadden G, Rothenburg S. Poxviruses and the evolution of host range and virulence. Infect Genet Evol. 2014 Jan;21C:15-40. Pubmedid: 24161410.
  • Chen H, Zheng D, Abbott J, Liu L, Bartee MY, Long M, Davids J, Williams J, Feldmann H, Strong J, Grau KR, Tibbetts S, Macaulay C, McFadden G, Thoburn R, Lomas DA, Spinale FG, Virgin HW, Lucas A. Myxomavirus-derived serpin prolongs survival and reduces inflammation and hemorrhage in an unrelated lethal mouse viral infection. Antimicrob Agents Chemother. 2013 Sep;57(9):4114-4127. Pubmedid: 23774438. Pmcid: PMC3754305.
  • Chan WM, Rahman MM, McFadden G. Oncolytic myxoma virus: the path to clinic. Vaccine. 2013 Sep;31(39):4252-4258. Pubmedid: 23726825. Pmcid: PMC3755036.
  • Bartee E, McFadden G. Cytokine synergy: an underappreciated contributor to innate anti-viral immunity. Cytokine. 2013 Sep;63(3):237-240. Pubmedid: 23693158. Pmcid: PMC3748162.
  • Zemp FJ, Lun X, McKenzie BA, Zhou H, Maxwell L, Sun B, Kelly JJ, Stechishin O, Luchman A, Weiss S, Cairncross JG, Hamilton MG, Rabinovich BA, Rahman MM, Mohamed MR, Smallwood S, Senger DL, Bell J, McFadden G, Forsyth PA. Treating brain tumor-initiating cells using a combination of myxoma virus and rapamycin. Neurooncol. 2013 Jul;15(7):904-920. Pubmedid: 23585629. Pmcid: PMC3688014.
  • Jenne CN, Wong CH, Zemp FJ, McDonald B, Rahman MM, Forsyth PA, McFadden G, Kubes P. Neutrophils recruited to sites of infection protect from virus challenge by releasing neutrophil extracellular traps. Cell Host Microbe. 2013 Feb;13(2):169-180. Pubmedid: 23414757.
  • Lemos de Matos A, McFadden G, Esteves PJ. Positive evolutionary selection on the RIG-I-like receptor genes in mammals. PLoS One. 2013;8(11):e81864. Pubmedid: 24312370. Pmcid: PMC3842351.
  • Li X, Schneider H, Peters A, Macaulay C, King E, Sun Y, Liu L, Dai E, Davids JA, McFadden G, Lucas A. Heparin alters viral serpin, serp-1, anti-thrombolytic activity to anti-thrombotic activity. Open Biochem J. 2011 Jul;2:6-15. Pubmedid: 18949070. Pmcid: PMC2570549.
  • France MR, Thomas DL, Liu J, McFadden G, MacNeill AL, Roy EJ. Intraventricular injection of myxoma virus results in transient expression of viral protein in mouse brain ependymal and subventricular cells. J Gen Virol. 2011 Jan;92(Pt 1):195-199. Pubmedid: 20861319.
  • Liu J, Wennier S, McFadden G. The immunoregulatory properties of oncolytic myxoma virus and their implications in therapeutics. Microbes Infect. 2010 Dec;12(14-15):1144-1152. Pubmedid: 20832500. Pmcid: PMC2998584.
  • Rahman MM, Madlambayan GJ, Cogle CR, McFadden G. Oncolytic viral purging of leukemic hematopoietic stem and progenitor cells with Myxoma virus. Cytokine Growth Factor Rev. 2010 Sep;21(2-3):169-175. Pubmedid: 20211576. Pmcid: PMC2881168.
  • Dai E, Liu LY, Wang H, McIvor D, Sun YM, Macaulay C, King E, Munuswamy-Ramanujam G, Bartee MY, Williams J, Davids J, Charo I, McFadden G, Esko JD, Lucas AR. Inhibition of chemokine-glycosaminoglycan interactions in donor tissue reduces mouse allograft vasculopathy and transplant rejection. PLoS One. 2010 Sep;5(5):e10510. Pubmedid: 20463901. Pmcid: PMC2865544.
  • Villa NY, Bartee E, Mohamed MR, Rahman MM, Barrett JW, McFadden G. Myxoma and vaccinia viruses exploit different mechanisms to enter and infect human cancer cells. Virology. 2010 Jun;401(2):266-279. Pubmedid: 20334889. Pmcid: PMC2862966.
  • Smallwood SE, Rahman MM, Smith DW, McFadden G. Myxoma virus: propagation, purification, quantification, and storage. Curr Protoc Microbiol. 2010 May;Chapter 14:Unit 14A.1. Pubmedid: 20440681. Pmcid: PMC2901999.
  • Werden SJ, McFadden G. Pharmacological manipulation of the akt signaling pathway regulates myxoma virus replication and tropism in human cancer cells. J Virol. 2010 Apr;84(7):3287-3302. Pubmedid: 20106927. Pmcid: PMC2838123.
  • Josiah DT, Zhu D, Dreher F, Olson J, McFadden G, Caldas H. Adipose-derived stem cells as therapeutic delivery vehicles of an oncolytic virus for glioblastoma. Mol Ther. 2010 Apr;18(2):377-385. Pubmedid: 19904233. Pmcid: PMC2839314.
  • Lun X, Alain T, Zemp FJ, Zhou H, Rahman MM, Hamilton MG, McFadden G, Bell J, Senger DL, Forsyth PA. Myxoma virus virotherapy for glioma in immunocompetent animal models: optimizing administration routes and synergy with rapamycin. Cancer Res. 2010 Jan;70(2):598-608. Pubmedid: 20068158.
  • McFadden G. Killing a killer: what next for smallpox?. PLoS Pathog. 2010 Jan;6(1):e1000727. Pubmedid: 20126444. Pmcid: PMC2813274.
  • Werden SJ, Lanchbury J, Shattuck D, Neff C, Dufford M, McFadden G. The myxoma virus m-t5 ankyrin repeat host range protein is a novel adaptor that coordinately links the cellular signaling pathways mediated by Akt and Skp1 in virus-infected cells. J Virol. 2009 Dec;83(23):12068-12083. Pubmedid: 19776120. Pmcid: PMC2786711.
  • Zhang L, Villa NY, Rahman MM, Smallwood S, Shattuck D, Neff C, Dufford M, Lanchbury JS, Labaer J, McFadden G. Analysis of vaccinia virus-host protein-protein interactions: validations of yeast two-hybrid screenings. J Proteome Res. 2009 Sep;8(9):4311-4318. Pubmedid: 19637933. Pmcid: PMC2738428.
  • Mohamed MR, Rahman MM, Lanchbury JS, Shattuck D, Neff C, Dufford M, van Buuren N, Fagan K, Barry M, Smith S, Damon I, McFadden G. Proteomic screening of variola virus reveals a unique NF-kappaB inhibitor that is highly conserved among pathogenic orthopoxviruses. Proc Natl Acad Sci U S A. 2009 Jun;106(22):9045-9050. Pubmedid: 19451633. Pmcid: PMC2683884.
  • Wang F, Gao X, Barrett JW, Shao Q, Bartee E, Mohamed MR, Rahman M, Werden S, Irvine T, Cao J, Dekaban GA, McFadden G. RIG-I mediates the co-induction of tumor necrosis factor and type I interferon elicited by myxoma virus in primary human macrophages. PLoS Pathog. 2008 Jul;4(7):e1000099. Pubmedid: 18617992. Pmcid: PMC2438611.
  • Stanford MM, Shaban M, Barrett JW, Werden SJ, Gilbert PA, Bondy-Denomy J, Mackenzie L, Graham KC, Chambers AF, McFadden G. Myxoma virus oncolysis of primary and metastatic B16F10 mouse tumors in vivo. Mol Ther. 2008 Jan;16(1):52-59. Pubmedid: 17998900.
  • Jiang J, Arp J, Kubelik D, Zassoko R, Liu W, Wise Y, Macaulay C, Garcia B, McFadden G, Lucas AR, Wang H. Induction of indefinite cardiac allograft survival correlates with toll-like receptor 2 and 4 downregulation after serine protease inhibitor-1 (Serp-1) treatment. Transplantation. 2007 Nov;84(9):1158-1167. Pubmedid: 17998872.
  • Barrett JW, Sypula J, Wang F, Alston LR, Shao Z, Gao X, Irvine TS, McFadden G. M135R is a novel cell surface virulence factor of myxoma virus. J Virol. 2007 Feb;81(1):106-114. Pubmedid: 17065210. Pmcid: PMC1797242.
  • McFadden G. Smallpox: an ancient disease enters the modern era of virogenomics. Proc Natl Acad Sci U S A. 2004 Oct;101(42):14994-14995. Pubmedid: 15479762. Pmcid: PMC524071.
  • Wang G, Barrett JW, Nazarian SH, Everett H, Gao X, Bleackley C, Colwill K, Moran MF, McFadden G. Myxoma virus M11L prevents apoptosis through constitutive interaction with Bak. J Virol. 2004 Jul;78(13):7097-7111. Pubmedid: 15194786. Pmcid: PMC421673.
  • Seet BT, McCaughan CA, Handel TM, Mercer A, Brunetti C, McFadden G, Fleming SB. Analysis of an orf virus chemokine-binding protein: Shifting ligand specificities among a family of poxvirus viroceptors. Proc Natl Acad Sci U S A. 2003 Dec;100(25):15137-15142. Pubmedid: 14657392. Pmcid: PMC299921.
  • Brunetti CR, Amano H, Ueda Y, Qin J, Miyamura T, Suzuki T, Li X, Barrett JW, McFadden G. Complete genomic sequence and comparative analysis of the tumorigenic poxvirus Yaba monkey tumor virus. J Virol. 2003 Dec;77(24):13335-13347. Pubmedid: 14645589. Pmcid: PMC296094.
  • Johnston JB, McFadden G. Poxvirus immunomodulatory strategies: current perspectives. J Virol. 2003 Jun;77(11):6093-6100. Pubmedid: 12743266. Pmcid: PMC155018.
  • Johnston JB, Barrett JW, Chang W, Chung CS, Zeng W, Masters J, Mann M, Wang F, Cao J, McFadden G. Role of the serine-threonine kinase PAK-1 in myxoma virus replication. J Virol. 2003 May;77(10):5877-5888. Pubmedid: 12719581. Pmcid: PMC154029.
  • Chang CS, McFadden G. Characterization of a pan-species reactive monoclonal antibody specific for a cell surface epitope which could serve as a marker for human monocytic and megakaryocytic differentiation. Hybrid Hybridomics. 2002 Dec;21(6):445-456. Pubmedid: 12573108.
  • Chang CS, McFadden G. Characterization of a monoclonal antibody specific for a novel primate cell surface marker with distinct biochemical properties on human erythroleukemia and myeloid cell lines. Hybrid Hybridomics. 2002 Aug;21(4):271-280. Pubmedid: 12193280.
  • Chen H, Davids JA, Zheng D, Bryant M, Bot I, van Berckel TJ, Biessen E, Pepine C, Ryman K, Progulski-Fox A, Kesavalu L, Moyer R, McFadden G, Lucas A. The serpin solution; targeting thrombotic and thrombolytic serine proteases in inflammation. Cardiovasc Hematol Disord Drug Targets. 2013 Aug;13(2):99-110. Pubmedid: 23987998.
  • Lucas A, Liu L, Dai E, Bot I, Viswanathan K, Munuswamy-Ramunujam G, Davids JA, Bartee MY, Richardson J, Christov A, Wang H, Macaulay C, Poznansky M, Zhong R, Miller L, Biessen E, Richardson M, Sullivan C, Moyer R, Hatton M, Lomas DA, McFadden G. The serpin saga; development of a new class of virus derived anti-inflammatory protein immunotherapeutics. Adv Exp Med Biol. 2009;666:132-156. Pubmedid: 20054981.
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