Goff Lab
Principal Investigator
Goff’s current work is centered on the study of the retrovirus life cycle and the host restriction systems that inhibit virus replication. His lab identified and characterized a novel host protein, termed ZAP for zinc finger antiviral protein, that blocks gene expression of many viruses, including the murine leukemia viruses, Ebola, Sindbis, and HIV-1, by degrading viral mRNAs and inhibiting their translation. Recent work has identified RIPLET, a signaling molecule in annate immunity, as a cofactor for ZAP. The lab has also characterized a protein complex responsible for the silencing of retroviral DNAs in embryonic stem (ES) cells, and identified a zinc finger protein, ZFP809, as an ES-cell specific recognition molecule that binds the proviral DNA and brings TRIM28 to locally modify chromatin. His lab is currently studying the chromatinization and silencing of incoming retroviral DNAs after acute infection, implicating several histone modifiers and the H1 linker histones as players in silencing of unintegrated HIV-1 DNAs. He is further interested in the role of endogenous viral proteins in tumor immunology.
Lab Members
Chunnan Dong
- Visiting Professor
Select Publications
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.
Wolf, D., and Goff, S.P. (2009) Embryonic stem cells use ZFP809 to silence retroviral DNAs. Nature 458, 1201-1204.
Metzger, M.J., 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.
Sabo, Y., de Los Santos, K., and Goff, S.P. (2020) IQGAP1 negatively regulates HIV-1 Gag trafficking and virion production. Cell Rep. 30, 4065-4081.e4.
Wang, G.Z., and Goff, S.P. (2020) Yin Yang 1 is a potent activator of human T lymphotropic virus type 1 LTR-driven gene expression via RNA binding. Proc. Natl. Acad. Sci. USA 117, 18701-18710.
Winans, S., and Goff, S.P. (2020) Mutations altering acetylated residues in the CTD of HIV-1 integrase cause defects in proviral transcription at early times after integration of viral DNA. PLoS Pathog. 16, e1009147.
Geis, F.K., Sabo, Y., Chen, X., Li, Y., Lu, C., and Goff, S.P. (2022) CHAF1A/B mediate silencing of unintegrated HIV-1 DNAs early in infection. Proc. Natl. Acad. Sci. USA 119, e2116735119.
Winans, S., Yu, H. J., de los Santos, K., Wang, G.Z., KewalRamani, V.N., and Goff, S.P. (2022) A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats. Nat. Commun. 13, 1474.
Buckmaster, M.V., and Goff, S.P. (2022) Riplet binds the zinc-finger antiviral protein (ZAP) and augments ZAP-mediated restriction of HIV-1. J. Virol. 96, e0052622.
Hart SFM, Yonemitsu MA, Giersch RM, Garrett FES, Beal BF, Arriagada G, Davis BW, Ostrander EA, Goff SP, Metzger MJ. Centuries of genome instability and evolution in soft-shell clam, Mya arenaria, bivalve transmissible neoplasia. Nat Cancer. 2023 Nov;4(11):1561-1574. doi: 10.1038/s43018-023-00643-7. Epub 2023 Oct 2.
Geis FK, Goff SP. Chromatin Immunoprecipitation of Retroviral Genomes with Antibodies Recognizing Modified Histones and Specific Viral Proteins. Methods Mol Biol. 2024;2807:163-171.