Stephen P. Goff, Ph.D.
Higgins Professor of Microbiology & Immunology and Biochemistry & Molecular Biophysics
Ph.D., Stanford University
Molecular biology of retrovirus replication; tyrosine kinases and signal transduction pathways
The central effort of our laboratory for several years has been a detailed genetic analysis of the replication cycle of the Moloney murine leukemia virus (M-MuLV) and the human immunodeficiency virus type 1 (HIV-1). The major approach has been to create mutations in cloned DNA copies of the viral genomes and to determine the effect of the mutations on the viral life cycle after transfer of the altered DNAs into cells in culture. These genetic analyses have defined the functional domains of various viral proteins and the sites of their action on viral nucleic acids. We have also expressed reverse transcriptase and integrase in bacteria and studied these enzymes biochemically. We make use of the yeast two-hybrid system to monitor protein-protein interactions between viral proteins, and to identify new host proteins that interact with the Gag, Pol and Env gene products. Finally, we use genetic selections in mammalian cells to screen overexpression libraries and gene knock-down libraries to identify genes that restrict virus replication or, alternatively, are essential for virus replication, especially those affecting intracellular trafficking of the viruses. Our work also addresses the control of retroviral gene expression in embryonic stem cells. Recently we have begun charactering a retroviral element associated with a leukemia-like disease in the mollusk Mya arenaria, the soft-shell clam.
Please see our lab website for more information about our members and research.
Zhu, Y., Wang, G.Z., Cingoz, O. and Goff, S.P. (2018) NP220 mediates silencing of unintegrated retroviral DNA. Nature 564:278-282.
Metzger, M.J., Paynter, A.N., Siddall, M.E. and Goff, S.P. (2018) Horizontal transfer of retrotransposons between bivalves and other aquatic species of multiple phyla. Proc. Natl. Acad. Sci. U.S.A. 115:E4227-E4235.
Cingoz, O. and Goff, S.P. (2018) Cyclin-dependent kinase activity is required for type I interferon production. Proc. Natl. Acad. Sci. U.S.A. 115:E2950-E2959.
Lee, A., Cingoz, O., Sabo, Y. and Goff, S.P. (2018) Characterization of interaction between Trim28 and YY1 in silencing proviral DNA of Moloney murine leukemia virus. Virology 516:165-175.
Zhu, Y., Luo, S., Sabo, Y., Wang, C., Tong, L. and Goff, S.P. (2017) Heme oxygenase 2 binds myristate to regulate retrovirus assembly and TLR4 signaling. Cell Host Microbe 21: 220-230.
Wang, C. and Goff, S.P. (2017) Differential control of retrovirus silencing in embryonic cells by proteasomal regulation of the ZFP809 retroviral repressor. Proc. Natl. Acad. Sci. U.S.A. 114:E922-E930.
Wang, G.Z., Wang, Y. and Goff, S.P. (2016) Histones are rapidly loaded onto unintegrated retroviral DNAs soon after nuclear entry. Cell Host Microbe 20: 798-809.
Metzger, M.J., Villalba, A., Carballal, M.J., Iglesias, D., Sherry, J., Reinisch, C., Muttray, A.F., Baldwin, S.A. and Goff, S.P. (2016) Widespread transmission of independent cancer lineages within multiple bivalve species. Nature 534: 705-709.
Green, L. and Goff, S.P. (2015) Translational readthrough-promoting drugs enhance pseudoknot-mediated suppression of the stop codon at the Moloney murine leukemia virus gag-pol junction. J. Gen. Virol. 96: 3411-3421.
Wang, G.Z. and Goff, S.P. (2015) Regulation of Yin Yang 1 by tyrosine phosphorylation. J. Biol. Chem. 290: 21890-21900.
Erazo, A. and Goff, S.P. (2015) Nuclear matrix protein Matrin 3 is a regulator of ZAP-mediated retroviral restriction. Retrovirology 12: 57.
Griffin, D.O. and Goff, S.P. (2015) HIV-1 is restricted prior to integration of viral DNA in primary cord-derived human CD34+ cells. J. Virol. 89: 8096-8100.
Metzger, MJ., Reinisch, C., Sherry, J., and Goff, S.P. (2015) Horizontal transmission of clonal cancer cells causes leukemia in soft-shell clams. Cell 161: 255-263.
Schlesinger, S., and Goff, S.P. (2015) Retroviral transcriptional regulation and embryonic stem cells: War and peace. Mol. Cell. Biol. 35: 770-777.
Wang, G.Z., and Goff, S.P. (2015) Postentry restriction of Mason-Pfizer monkey virus in mouse cells. J. Virol. 89: 2813-2819.
Kao, T.-H., Liao, H.-F., Wolf, D., Tai, K.-Y., Chuang, C.-Y., Lee, H.-S., Kuo, H.-C., Hata, K., Zhang, X., Cheng, X., Goff, S.P., Ooi, S.K., Bestor, T.H., and Lin, S.-P. (2014) Ectopic DNMT3L triggers assembly of a repressive complex for retroviral silencing in somatic cells. J. Virol. 88: 10680-10695.
Arriagada, G., Metzger, M.J., Muttray, A., Sherry, J., Reinisch, C., Street, C., Lipkin, W.I., and Goff, S.P. (2014) Activation of transcription and retrotransposition of a novel retroelement, Steamer, in neoplastic hemocytes of the mollusk Mya arenaria. Proc. Natl. Acad. Sci. U.S.A.111:14175-14180.
Schlesinger, S., Meshorer, E. and Goff, S.P. (2014) Asynchronous transcriptional silencing of individual retroviral genomes in embryonic cells. Retrovirology 11: e31.
Wang, G.Z., Wolf, D. and Goff, S.P. (2013) EBP1, a novel host factor involved in Primer Binding Site (PBS)-dependent restriction of Moloney murine leukemia virus in embryonic cells. J. Virol.88: 1825-1829.
Goff, S.P. (2013) HIV: Slipping under the radar. Nature News and Views 503: 352-353.
Schlesinger, S., Lee, A., Wang, G.Z., Green, L. and Goff, S.P. (2013) Proviral silencing in embryonic cells is regulated by Yin Yang 1. Cell Rep. 4: 1-9.
Schlesinger, S. and Goff, S.P. (2013) Silencing of proviruses in embryonic cells: Efficiency, stability, and chromatin modifications. EMBO Rep. 14: 73-79.
Green, L., Houck-Loomis, B., Yueh, A. and Goff, S.P. (2012) Large ribosomal protein 4 increases efficiency of viral recoding sequences. J Virol. 86: 8949-8958.
Arriagada, G., Muntean, L.N. and Goff, S.P. (2011) SUMO-interacting motifs of human TRIM5alpha are important for antiviral activity. PLoS Pathog. 7: e1002019.
Hogg, J.R. and Goff, S.P. (2010) Upf1 senses 3' UTR length to potentiate mRNA decay. Cell143: 379-389.
Qiu, Z.Z., Cang, Y. and Goff S.P. (2010) c-Abl tyrosine kinase regulates cardiac growth and development. Proc. Natl. Acad. Sci. U.S.A. 107: 1136-1141.
Valente, S.T., Gilmartin, G.M., Venkataraman, K. and Goff, S.P. (2009) HIV-1 mRNA 3' end processing is distinctively regulated by eIF3f, CDK11, and splice factor 9G8. Mol. Cell 36:279-289.
Wolf, D. and Goff, S.P. Embryonic stem cells use ZFP809 to silence retroviral DNAs. (2009) Nature 458: 1201-1204.
Valente, S.T., Gilmartin, G.M., Mott, C., Falkard, B. and Goff S.P. (2009) Inhibition of HIV-1 replication by eIF3f. Proc. Natl. Acad. Sci. U.S.A. 106: 4071-4078.
Wolf, D., Hug, K. and Goff S.P. (2008) TRIM28 mediates primer binding site-targeted silencing of Lys1,2 tRNA-utilizing retroviruses in embryonic cells. Proc. Natl. Acad. Sci. USA 105, 12521-12526.
Wolf, D. and Goff, S.P. (2007) TRIM28 mediates primer binding site-targeted silencing of murine leukemia virus in embryonic cells. Cell 131: 46-57.
Cang, Y., Zhang, J., Nicholas, S.A., Kim, A.L., Zhou, P. and Goff, S.P. (2007) DDB1 is essential for genomic stability in developing epidermis. Proc. Natl. Acad. Sci. USA 104: 2733-2737.
Cang, Y., Zhang, J., Nicholas, S.A., Bastien, J., Li, B., Zhou, P. and Goff, S.P. (2006) Deletion of DDB1 in mouse brain and lens leads to p53-dependent elimination of proliferating cells. Cell127: 929-940.
Naghavi, M.H., Hatziioannou, T., Gao, G. and Goff S.P. (2005) Overexpression of fasciculation and elongation protein zeta-1 (FEZ1) induces a post-entry block to retroviruses in cultured cells. Genes Dev. 19: 1105-1115.
Evans, M.J., Rice, C.M. and Goff, S.P. (2004) Phosphorylation of Hepatitis C virus NS5A modulates its protein interactions and viral RNA replication. Proc. Natl. Acad. Sci. U.S.A. 101:13038-13043.
Orlova, M., Yueh, A., Leung, J. and Goff, S.P. (2003) Reverse transcriptase of Moloney murine leukemia virus binds to eukaryotic release factor 1 to modulate suppression of translational termination. Cell 115: 319-331.
Gao, G., Guo, X. and Goff, S.P. (2002) Inhibition of retroviral RNA production by ZAP, a novel CCCH-type zinc finger protein. Science 297: 1703-1706.
Tachedjian, G., Orlova, M., Sarafianos, S., Arnold, E. and Goff, S.P. (2001) Nonnucleoside reverse transcriptase inhibitors are chemical enhancers of dimerization of the HIV type1 reverse transcriptase. Proc. Natl. Acad. Sci. U.S.A. 98: 7188-7193.
Li, B., Boast, S., de los Santos, K., Schieren, I., Quiroz, M., Teitelbaum, S.L., Tondravi, M.M. and Goff, S.P. (2000) Mice deficient in Abl are osteoporotic and have defects in osteoblast maturation. Nat. Genet. 24: 304-308.
Yuan, B., Li, X. and Goff, S.P. (1999) Mutations altering the Moloney murine leukemia virus p12 Gag protein affect virion production and early events of the virus life cycle. EMBO J. 18: 4700-4710.