Department of Microbiology & Immunology

Columbia University Medical Center
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

Research
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.

Selected Publications

  1. 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.
  2. 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. Epub 2011 Apr 7.
  3. Hogg, J.R. and Goff, S.P. (2010) Upf1 senses 3' UTR length to potentiate mRNA decay. Cell 143: 379-389.
  4. 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.
  5. 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.
  6. Wolf, D. and Goff, S.P. Embryonic stem cells use ZFP809 to silence retroviral DNAs. (2009) Nature 458: 1201-1204.
  7. 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.
  8. 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.
  9. 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.
  10. 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.
  11. 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. Cell 127: 929-940.
  12. 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.
  13. 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.
  14. 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.
  15. 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.
  16. 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.
  17. 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.
  18. 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.

Professor Stephen P. Goff
Phone: 212-305-3794
Lab Phone: 212-305-7956
Fax: 212-305-5106
Email:  spg1@columbia.edu
Website: www.microbiology.columbia.edu/goff


Department of Microbiology & Immunology, Columbia University + 701 W. 168 St., HHSC 1208 New York, NY 10032 Tel. 212-305-3647