Betty L. Slagle

(713) 798-3006

Email

bslagle@bcm.edu

Professional Interests

Pathogenesis of viral hepatitis

Professional Statement

Chronic infection with hepatitis B virus (HBV) affects approximately 350 million people worldwide and constitutes a significant risk factor for severe liver disease, including hepatocellular carcinoma (HCC). HBx is the sole regulatory protein encoded by HBV. It is required for virus replication, and has a cancer cofactor role in HBx transgenic mice. New plasmid-based HBV replication assays provide an opportunity to evaluate HBx function in the context of virus replication, and in a biologically relevant setting. The long-term goal of our research is to identify the function provided by HBx that is critical for virus replication. The information generated may allow us to identify new cellular targets through which to disrupt chronic virus replication and prevent serious liver pathology and HCC.

Selected Publications

Marriott SJ, Lee TH, Slagle BL, Butel JS. " Activation of the HTLV-I long terminal repeat by the hepatitis B virus X protein. " Virology. 1996 Oct 1; 224 (1) : 206-13.
Pubmed PMID: 8862415.
Hsu HC, Peng SY, Lai PL, Sheu JC, Chen DS, Lin LI, Slagle BL, Butel JS. " Allelotype and loss of heterozygosity of p53 in primary and recurrent hepatocellular carcinomas. A study of 150 patients. " Cancer. 1994 Jan 1; 73 (1) : 42-7.
Pubmed PMID: 7506118.
Madden CR, Finegold MJ, Slagle BL. " Altered DNA mutation spectrum in aflatoxin b1-treated transgenic mice that express the hepatitis B virus x protein. " J. Virol.. 2002 Nov ; 76 (22) : 11770-4.
Pubmed PMID: 12388740.
Nath A, Slagle B, Wolinsky JS. " Anti-idiotypic antibodies to rubella virus. " Arch. Virol.. 1989 ; 107 (41276) : 159-67.
Pubmed PMID: 2803003.
Nag A, Datta A, Yoo K, Bhattacharyya D, Chakrabortty A, Wang X, Slagle BL, Costa RH, Raychaudhuri P. " DDB2 induces nuclear accumulation of the hepatitis B virus X protein independently of binding to DDB1. " J. Virol.. 2001 Nov ; 75 (21) : 10383-92.
Pubmed PMID: 11581406.
Slagle BL, Zhou YZ, Birchmeier W, Scorsone KA. " Deletion of the E-cadherin gene in hepatitis B virus-positive Chinese hepatocellular carcinomas. " Hepatology. 1993 Oct ; 18 (4) : 757-62.
Pubmed PMID: 8104855.
Sepulveda AR, Finegold MJ, Smith B, Slagle BL, DeMayo JL, Shen RF, Woo SL, Butel JS. " Development of a transgenic mouse system for the analysis of stages in liver carcinogenesis using tissue-specific expression of SV40 large T-antigen controlled by regulatory elements of the human alpha-1-antitrypsin gene. " Cancer Res.. 1989 Nov 1; 49 (21) : 6108-17.
Pubmed PMID: 2551499.
Wentz MJ, Becker SA, Slagle BL. " Dissociation of DDB1-binding and transactivation properties of the hepatitis B virus X protein. " Virus Res.. 2000 Jun ; 68 (1) : 87-92.
Pubmed PMID: 10930665.
Connolly E, Melegari M, Landgraf P, Tchaikovskaya T, Tennant BC, Slagle BL, Rogler LE, Zavolan M, Tuschl T, Rogler CE. " Elevated expression of the miR-17-92 polycistron and miR-21 in hepadnavirus-associated hepatocellular carcinoma contributes to the malignant phenotype. " Am. J. Pathol.. 2008 Sep ; 173 (3) : 856-64.
Pubmed PMID: 18688024.
Xu Z, Yen TS, Wu L, Madden CR, Tan W, Slagle BL, Ou JH. " Enhancement of hepatitis B virus replication by its X protein in transgenic mice. " J. Virol.. 2002 Mar ; 76 (5) : 2579-84.
Pubmed PMID: 11836439.
Keasler VV, Hodgson AJ, Madden CR, Slagle BL. " Enhancement of hepatitis B virus replication by the regulatory X protein in vitro and in vivo. " J. Virol.. 2007 Mar ; 81 (6) : 2656-62.
Pubmed PMID: 17182675.
Madden CR, Finegold MJ, Slagle BL. " Expression of hepatitis B virus X protein does not alter the accumulation of spontaneous mutations in transgenic mice. " J. Virol.. 2000 Jun ; 74 (11) : 5266-72.
Pubmed PMID: 10799603.
Slagle BL, Lanford RE, Medina D, Butel JS. " Expression of mammary tumor virus proteins in preneoplastic outgrowth lines and mammary tumors of BALB/cV mice. " Cancer Res.. 1984 May ; 44 (5) : 2155-62.
Pubmed PMID: 6324998.
Slagle BL, Kaufman RH, Reeves WC, Icenogle JP. " Expression of ras, c-myc, and p53 proteins in cervical intraepithelial neoplasia. " Cancer. 1998 Oct 1; 83 (7) : 1401-8.
Pubmed PMID: 9762942.
Becker SA, Zhou YZ, Slagle BL. " Frequent loss of chromosome 8p in hepatitis B virus-positive hepatocellular carcinomas from China. " Cancer Res.. 1996 Nov 1; 56 (21) : 5092-7.
Pubmed PMID: 8895769.
Slagle BL, Lee TH, Butel JS. " Hepatitis B virus and hepatocellular carcinoma. " Prog. Med. Virol.. 1992 ; 39 : 167-203.
Pubmed PMID: 1317597.
Keasler VV, Hodgson AJ, Madden CR, Slagle BL. " Hepatitis B virus HBx protein localized to the nucleus restores HBx-deficient virus replication in HepG2 cells and in vivo in hydrodynamically-injected mice. " Virology. 2009 Jul 20; 390 (1) : 122-9.
Pubmed PMID: 19464721.
Slagle BL, Zhou YZ, Butel JS. " Hepatitis B virus integration event in human chromosome 17p near the p53 gene identifies the region of the chromosome commonly deleted in virus-positive hepatocellular carcinomas. " Cancer Res.. 1991 Jan 1; 51 (1) : 49-54.
Pubmed PMID: 1670994.
Hodgson AA, Hyser JM, Keasler VV, Cang Y, Slagle BL. " Hepatitis B virus regulatory HBx protein binding to DDB1 is required but is not sufficient for maximal HBV replication. " Virology. 2012 Apr 25; 426 (1) : 73-82.
Pubmed PMID: 22342275.
Kumar M, Jung SY, Hodgson AJ, Madden CR, Qin J, Slagle BL. " Hepatitis B Virus Regulatory HBx Protein Binds to Adaptor Protein IPS-1 and Inhibits the Activation of Beta Interferon. " J. Virol.. 2011 Jan ; 85 (2) : 987-95.
Pubmed PMID: 21068253.
Madden CR, Finegold MJ, Slagle BL. " Hepatitis B virus X protein acts as a tumor promoter in development of diethylnitrosamine-induced preneoplastic lesions. " J. Virol.. 2001 Apr ; 75 (8) : 3851-8.
Pubmed PMID: 11264374.
Becker SA, Lee TH, Butel JS, Slagle BL. " Hepatitis B virus X protein interferes with cellular DNA repair. " J. Virol.. 1998 Jan ; 72 (1) : 266-72.
Pubmed PMID: 9420223.
Chomarat P, Rice JM, Slagle BL, Wild CP. " Hepatitis B virus-induced liver injury and altered expression of carcinogen metabolising enzymes: the role of the HBx protein. " Toxicol. Lett.. 1998 Dec 28; 102 : 595-601.
Pubmed PMID: 10022319.
Slagle BL, Butel JS. " Identification and characterization of a mouse mammary tumor virus protein uniquely expressed on the surface of BALB/cV mammary tumor cells. " Virology. 1985 May ; 143 (1) : 127-42.
Pubmed PMID: 2997998.
Donehower LA, Slagle BL, Wilde M, Darlington G, Butel JS. " Identification of a conserved sequence in the non-coding regions of many human genes. " Nucleic Acids Res.. 1989 Jan 25; 17 (2) : 699-710.
Pubmed PMID: 2536922.
Keasler VV, Lerat H, Madden CR, Finegold MJ, McGarvey MJ, Mohammed EM, Forbes SJ, Lemon SM, Hadsell DL, Grona SJ, Hollinger FB, Slagle BL. " Increased liver pathology in hepatitis C virus transgenic mice expressing the hepatitis B virus X protein. " Virology. 2006 Apr 10; 347 (2) : 466-75.
Pubmed PMID: 16427673.
Slagle BL, Lee TH, Medina D, Finegold MJ, Butel JS. " Increased sensitivity to the hepatocarcinogen diethylnitrosamine in transgenic mice carrying the hepatitis B virus X gene. " Mol. Carcinog.. 1996 Apr ; 15 (4) : 261-9.
Pubmed PMID: 8634084.
Khaoustov VI, Ozer A, Smith JR, Noda A, Mearns M, Krishnan B, Slagle BL, Yoffe B. " Induction of senescent cell-derived inhibitor of DNA synthesis gene, SDI1, in hepatoblastoma (HepG2) cells arrested in the G2-phase of the cell cycle by 9-nitrocamptothecin. " Lab. Invest.. 1995 Jul ; 73 (1) : 118-27.
Pubmed PMID: 7603034.
Butel JS, Lee TH, Slagle BL. " Is the DNA repair system involved in hepatitis-B-virus-mediated hepatocellular carcinogenesis? " Trends Microbiol.. 1996 Mar ; 4 (3) : 119-24.
Pubmed PMID: 8868091.
Slagle BL, Medina D, Butel JS. " Mammary cancer stages in BALB/cV mice: mouse mammary tumor virus expression and virus-host interactions. " J. Natl. Cancer Inst.. 1987 Aug ; 79 (2) : 323-35.
Pubmed PMID: 3037152.
Donehower LA, Harvey M, Slagle BL, McArthur MJ, Montgomery CA, Butel JS, Bradley A. " Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours. " Nature. 1992 Mar 19; 356 (6366) : 215-21.
Pubmed PMID: 1552940.
Slagle BL, Wheeler DA, Hager GL, Medina D, Butel JS. " Molecular basis of altered mouse mammary tumor virus expression in the D-2 hyperplastic alveolar nodule line of BALB/c mice. " Virology. 1985 May ; 143 (1) : 41289.
Pubmed PMID: 2414907.
Longato L, de la Monte S, Kuzushita N, Horimoto M, Rogers AB, Slagle BL, Wands JR. " Overexpression of insulin receptor substrate-1 and hepatitis Bx genes causes premalignant alterations in the liver. " Hepatology. 2009 Jun ; 49 (6) : 1935-43.
Pubmed PMID: 19475691.
Slagle BL. " p53 mutations and hepatitis B virus: cofactors in hepatocellular carcinoma. " Hepatology. 1995 Feb ; 21 (2) : 597-9.
Pubmed PMID: 7843736.
Scorsone KA, Zhou YZ, Butel JS, Slagle BL. " p53 mutations cluster at codon 249 in hepatitis B virus-positive hepatocellular carcinomas from China. " Cancer Res.. 1992 Mar 15; 52 (6) : 1635-8.
Pubmed PMID: 1311638.
Hodgson AJ, Keasler VV, Slagle BL. " Premature cell cycle entry induced by hepatitis B virus regulatory HBx protein during compensatory liver regeneration. " Cancer Res.. 2008 Dec 15; 68 (24) : 10341-8.
Pubmed PMID: 19074903.
Madden CR, Slagle BL. " Stimulation of cellular proliferation by hepatitis B virus X protein. " Dis. Markers. 2001 ; 17 (3) : 153-7.
Pubmed PMID: 11790880.
Zhou YZ, Slagle BL, Donehower LA, vanTuinen P, Ledbetter DH, Butel JS. " Structural analysis of a hepatitis B virus genome integrated into chromosome 17p of a human hepatocellular carcinoma. " J. Virol.. 1988 Nov ; 62 (11) : 4224-31.
Pubmed PMID: 2845134.
Luo N, Cai Y, Zhang J, Tang W, Slagle BL, Wu X, He S. " The C-terminal region of the hepatitis B virus X protein is required for its stimulation of HBV replication in primary mouse hepatocytes. " Virus Res.. 2012 May ; 165 (2) : 170-8.
Pubmed PMID: 22387566.
Shiyanov P, Hayes SA, Donepudi M, Nichols AF, Linn S, Slagle BL, Raychaudhuri P. " The naturally occurring mutants of DDB are impaired in stimulating nuclear import of the p125 subunit and E2F1-activated transcription. " Mol. Cell. Biol.. 1999 Jul ; 19 (7) : 4935-43.
Pubmed PMID: 10373543.
Jaitovich-Groisman I, Benlimame N, Slagle BL, Perez MH, Alpert L, Song DJ, Fotouhi-Ardakani N, Galipeau J, Alaoui-Jamali MA. " Transcriptional regulation of the TFIIH transcription repair components XPB and XPD by the hepatitis B virus x protein in liver cells and transgenic liver tissue. " J. Biol. Chem.. 2001 Apr 27; 276 (17) : 14124-32.
Pubmed PMID: 11278765.
Butel JS, Lee TH, Slagle BL. " Viral co-factors in liver cancer: lessons from hepatitis B virus. " Int. Symp. Princess Takamatsu Cancer Res. Fun. 1995 ; 25 : 185-98.
Pubmed PMID: 8875624.

Skills

Betty Slagle