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Our laboratory is interested in the replication of mammalian retroviruses, including the human immunodeficiency virus (HIV) and Moloney murine leukemia virus (M-MuLV). The major approach has been to alter cloned DNA copies of the viral genome by site-directed mutagenesis, and to determine the effects of these 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. Recently, we have applied 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. Others in the group are interested in the functions of several viral oncogenes, especially the tyrosine kinases v-abl and v-src, and other signal transduction molecules, including the axl/ark receptor kinase; mpl, the thrombopoietin receptor; pdeg, the retinal cGMP phosphodiesterase; and various cytokine receptors. Finally, embryonic stem cell technologies are being used to generate knock-out mice deficient in these transduction molecules.

Selected Publications

Gao, G., and Goff, S.P. (1999) Somatic cell mutants resistant to retrovirus replication: Intracellular blocks during the early stages of infection. Mol. Biol. Cell 10, 1705-1717.

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.

Li, B., Boast, S., de los Santos, K., Schieren, I., Quiroz, M., Teitelbaum, S.L., Tondravi, M.M., and Goff, S.P. (2000) c-Abl mutant mice are osteoporotic and show defects in osteoblast maturation. Nat. Genet. 24, 304-308.

Tachedjian, G., Aronson, H.-E. G., and Goff, S.P. (2000) Analysis of mutations and suppressors affecting interactions between the subunits of the human immunodeficiency virus type 1 reverse transcriptase. Proc. Natl. Acad. Sci. USA 97, 6334-6339.

Fan, P.D., and Goff, S.P. (2000) Abi-1 binds to Sos and inhibits EGF- and v-Abl-induced activation of Extracellular Signal-Regulated Kinases. Mol. Cell. Biol. 20, 7591-7601.