Miller, I George - Yale University - Biological & Biomedical Sciences

个人简介

Dr. Miller’s laboratory studies the mechanisms underlying the switch between latency and lytic replication of two oncogenic herpesviruses, Epstein-Barr virus and Kaposi’s sarcoma-associated herpesvirus. Current experiments explore how viral and cellular transcription factors that selectively bind to methylated DNA control expression of viral and cellular genes, how cellular gene expression is selectively inhibited while viral gene expression is enhanced, and how viral DNA replication is regulated by cellular proteins. Recent studies focus on a new class of anti-viral agents that inhibit reactivation of Epstein-Barr virus from latency into lytic infection. AB Harvard College (1968) MD Harvard Medical School (1962) Research Fellow Children's Hospital, Boston Research Fellow Harvard Medical School Intern & Assistant Resident University Hospital, Cleveland Board Certification AB of Internal Medicine, Internal Medicine (1972)

研究领域

Biophysics; Pediatrics; Sarcoma, Kaposi; Virology; Epstein-Barr Virus Infections; Infectious Disease Medicine

近期论文

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Binding of RBP-Jkappa (CSL) protein to the promoter of the Kaposi's sarcoma-associated herpesvirus ORF47 (gL) gene is a critical but not sufficient determinant of transactivation by ORF50 protein. Chang PJ1, Boonsiri J, Wang SS, Chen LY, Miller G. Binding of RBP-Jkappa (CSL) protein to the promoter of the Kaposi's sarcoma-associated herpesvirus ORF47 (gL) gene is a critical but not sufficient determinant of transactivation by ORF50 protein. Virology. 2010 Mar 1;398(1):38-48. Upregulation of STAT3 marks Burkitt lymphoma cells refractory to Epstein-Barr virus lytic cycle induction by HDAC inhibitors. Daigle, D., Megyola, C., El-Guindy, A., Gradoville, G., Tuck, D., Miller, G. and Bhaduri-McIntosh, S. Up-regulation of STAT3 Marks Burkitt Lymphoma Cells Refractory to Epstein-Barr Virus Lytic Cycle Induction by HDAC Inhibitors. J. Virology 84:993-1004, Complex N-linked glycans on Asn-89 of Kaposi sarcoma herpes virus-encoded interleukin-6 mediate optimal function by affecting cytokine protein conformation. Dela Cruz CS, Viswanathan SR, El-Guindy AS, Shedd D, Miller G. Complex N-linked glycans on Asn-89 of Kaposi sarcoma herpes virus-encoded interleukin-6 mediate optimal function by affecting cytokine protein conformation. J Biol Chem. 2009 Oct 23;284(43):29269-82 Stimulus duration and response time independently influence the kinetics of lytic cycle reactivation of Epstein-Barr virus. Countryman J, Gradoville L, Bhaduri-McIntosh S, Ye J, Heston L, Himmelfarb S, Shedd D, Miller G. Stimulus duration and response time independently influence the kinetics of lytic cycle reactivation of Epstein-Barr virus. J Virol. 2009 Oct;83(20):10694-709 Two phenylalanines in the C-terminus of Epstein-Barr virus Rta protein reciprocally modulate its DNA binding and transactivation function. Chen LW, Raghavan V, Chang PJ, Shedd D, Heston L, Delecluse HJ, Miller G. Two phenylalanines in the C-terminus of Epstein-Barr virus Rta protein reciprocally modulate its DNA binding and transactivation function. Virology. 2009 Apr 10;386(2):448-61 Mutations of amino acids in the DNA-recognition domain of Epstein-Barr virus ZEBRA protein alter its sub-nuclear localization and affect formation of replication compartments. Park R, Heston L, Shedd D, Delecluse HJ, Miller G. Delecluse and G. Miller.Mutations of amino acids in the DNA-recognition domain of Epstein-Barr virus ZEBRA protein alter its sub-nuclear localization and affect formation of replication compartments. Virology. 2008 Dec 20;382(2):145-62 Ornaghi S, Davis JN, Gorres KL, Miller G, Paidas MJ, van den Pol AN: Mood stabilizers inhibit cytomegalovirus infection. Virology. 2016 Dec; 2016 Sep 19. PMID: 27657833 Gorres KL, Daigle D, Mohanram S, McInerney GE, Lyons DE, Miller G: Valpromide Inhibits Lytic Cycle Reactivation of Epstein-Barr Virus. MBio. 2016 Mar 1; 2016 Mar 1. PMID: 26933051 Wang'ondu R, Teal S, Park R, Heston L, Delecluse H, Miller G: DNA Damage Signaling Is Induced in the Absence of Epstein-Barr Virus (EBV) Lytic DNA Replication and in Response to Expression of ZEBRA. PLoS One. 2015; 2015 May 7. PMID: 25950714 El-Guindy A, Lopez-Giraldez F, Delecluse HJ, McKenzie J, Miller G: A locus encompassing the Epstein-Barr virus bglf4 kinase regulates expression of genes encoding viral structural proteins. PLoS Pathog. 2014 Aug; 2014 Aug 28. PMID: 25166506 Gorres KL, Daigle D, Mohanram S, Miller G: Activation and repression of Epstein-Barr Virus and Kaposi's sarcoma-associated herpesvirus lytic cycles by short- and medium-chain fatty acids. J Virol. 2014 Jul; 2014 May 7. PMID: 24807711 Park R, El-Guindy A, Heston L, Lin SF, Yu KP, Nagy M, Borah S, Delecluse HJ, Steitz J, Miller G: Nuclear translocation and regulation of intranuclear distribution of cytoplasmic poly(A)-binding protein are distinct processes mediated by two Epstein Barr virus proteins. PLoS One. 2014; 2014 Apr 4. PMID: 24705134 Yu KP, Heston L, Park R, Ding Z, Wang'ondu R, Delecluse HJ, Miller G: Latency of Epstein-Barr virus is disrupted by gain-of-function mutant cellular AP-1 proteins that preferentially bind methylated DNA. Proc Natl Acad Sci U S A. 2013 May 14; 2013 Apr 26. PMID: 23625009 El-Guindy A, Ghiassi-Nejad M, Golden S, Delecluse HJ, Miller G: Essential role of Rta in lytic DNA replication of Epstein-Barr virus. J Virol. 2013 Jan; 2012 Oct 17. PMID: 23077295 Daigle D, Gradoville L, Tuck D, Schulz V, Wang'ondu R, Ye J, Gorres K, Miller G: Valproic acid antagonizes the capacity of other histone deacetylase inhibitors to activate the Epstein-barr virus lytic cycle. J Virol. 2011 Jun; 2011 Mar 16. PMID: 21411522 Park R, Wang'ondu R, Heston L, Shedd D, Miller G: Efficient induction of nuclear aggresomes by specific single missense mutations in the DNA-binding domain of a viral AP-1 homolog. J Biol Chem. 2011 Mar 18; 2011 Jan 13. PMID: 21233201 Ye J, Gradoville L, Miller G: Cellular immediate-early gene expression occurs kinetically upstream of Epstein-Barr virus bzlf1 and brlf1 following cross-linking of the B cell antigen receptor in the Akata Burkitt lymphoma cell line. J Virol. 2010 Dec; 2010 Sep 22. PMID: 20861250 El-Guindy A, Heston L, Miller G: A subset of replication proteins enhances origin recognition and lytic replication by the Epstein-Barr virus ZEBRA protein. PLoS Pathog. 2010 Aug 19; 2010 Aug 19. PMID: 20808903 Daigle D, Megyola C, El-Guindy A, Gradoville L, Tuck D, Miller G, Bhaduri-McIntosh S: Upregulation of STAT3 marks Burkitt lymphoma cells refractory to Epstein-Barr virus lytic cycle induction by HDAC inhibitors. J Virol. 2010 Jan; 2009 Nov 4. PMID: 19889776