Adam P. Geballe

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Fred Hutchinson Cancer Research Center
Human Biology Division
Appointed: 1999
University of Washington
School of Medicine
Medicine
Allergy and Infectious Diseases
ProfessorAppointed: 2004
Fred Hutchinson Cancer Research Center
Clinical Research Division
Appointed: 1999
Professional Headshot of Adam P. Geballe

Mailing Address

Fred Hutchinson Cancer Research Center
1100 Fairview Avenue N.
P.O. Box 19024
C2-023
Seattle, Washington 98109-1024
United States

Contact Information

Phone: (206) 667-5122
Fax: (206) 667-6523
ageballe@fhcrc.org

Qualifications

M.D., Duke University, Medicine, 1978.

Expertise and Research Interests

Translational regulation of viral and cellular gene expression

Studies in an increasing number of systems demonstrate that translational events have a major impact on eukaryotic gene expression. Research in the Geballe lab aims to identify the cis-acting signals and trans-acting factors and to elucidate the mechanisms that regulate expression of viral and cellular genes at the translational level.

Human cytomegalovirus (HCMV), a member of the herpesvirus family, typically produces few if any symptoms in otherwise healthy individuals, but often causes life-threatening infections in newborns, solid organ and hematopoietic stem cell transplant recipients, and other immunocompromised patients. In addition to its medical importance, HCMV is also a useful model system for the study of translational regulation of eukaryotic gene expression. Host cells respond to viral infections by activating several antiviral pathways, including ones that are triggered by interferons and activated by double-stranded RNA (dsRNA), and that act by shutting off protein synthesis. To enable the continued protein synthesis that is necessary for replication, many viruses including HCMV have evolved means of inactivating these pathways. A genetic screen identified two HCMV genes that participate in maintaining translational capacity in the infected cell despite activation of these host responses. These genes bind to dsRNA through an unconventional dsRNA binding domain and a PKR binding domain, both of which are necessary for blocking the antiviral pathways. The protein also self-associate. These proteins also cause PKR relocalization to the nucleus, an unprecendented effect among viral anti-PKR protein. A related virus, Mouse CMV, has genes of similar function and comparisons between the human and mouse viruses will be useful in identifying conserved critical functions. Current efforts aim to elucidate the activities of the various domains of these genes and to identify other viral and cellular factors needed to maintain the robust protein synthetic capacity in CMV-infected cells.

Keywords

COS Keywords:

Allergy, Bone Marrow Transplantation, Cell Biology, Clinical Research Or Studies, Gene Expression, HIV, Infectious Diseases Or Agents, Mental Retardation, Peptides, Proteins and Macromolecules, Virology.

Additional Terms:

Cytomegalovirus, Fragile X Mental Retardation (FMR1), HER-2/neu, Translation Termination, Translational Control, UL4, Upstream ORFs.

Publications

  • Hakki, M. (2007) Cytomegalovirus, Sexually Transmitted Diseases, 4th Edition, McGraw Hill, In Press (bookchapter)
  • Sachs, M.S. and A.P. Geballe (2006) Downstream control of upstream open reading frames, Genes and Development, 20 (8), 915-921
  • Child, S.J., L.K. Hanson, C.E. Brown (2006) Double-stranded RNA-binding by a heterodimeric complex of murine cytomegalovirus m142 and m143 proteins, Journal of Virology, 80, 10173-10180
  • Hakki, M. (2006) Binding and nuclear relocalization of PKR by human cytomegalovirus TRS1, Journal of Virology, 80, 11817-11826
  • Spevak, C.C. (2006) . Her-2 upstream open reading frame effects on the use of downstream initiation codons, BBRC, 350, 834-841
  • Hakki, M and A.P. Geballe (2005) Double-stranded RNA binding by human cytomegalovirus pTRS1, Journal of Virology, 79 (12), 7311-7318
  • Child SJ, Hakki M, De Niro KL, Geballe AP, Evasion of cellular antiviral responses by human cytomegalovirus TRS1 and IRS1, Journal of Virology, 78(1), 197-205, 2004 Abstract
  • Janzen DM, Geballe AP, The effect of eukaryotic release factor depletion on translation termination in human cell lines, Nucleic Acids Research, 32(15), 4491-502, 2004 Abstract
  • Scott, J.D., J.A. Englund, D. Myerson, A.P. Geballe, Influenza pneumonia presenting as progressive focal infiltrates in a stem cell transplant recipient, Journal of Clinical Virology, 31(96), 99, 2004
  • Janzen DM, Frolova L, Geballe AP, Inhibition of translation termination mediated by an interaction of eukaryotic release factor 1 with a nascent peptidyl-tRNA, Molecular and Cellular Biology, 22(24), 8562-8570, December 2002
  • Sachs MS, Geballe AP, Biochemistry. Sense and sensitivity--controlling the ribosome, Science, 297(5588), 1820-1, September 2002 Abstract
  • Child SJ, Jarrahian S, Harper VM, Geballe AP, Complementation of vaccinia virus lacking the double-stranded RNA-binding protein gene E3L by human cytomegalovirus, Journal of Virology, 76(10), 4912-8, May 2002 Abstract
  • Alderete JP, Child SJ, Geballe AP, Abundant early expression of gpUL4 from a human cytomegalovirus mutant lacking a repressive upstream open reading frame, Journal of Virology, 75(15), 7188-92, August 2001 Abstract
  • Bar M, Shannon-Lowe C, Geballe AP, Differentiation of human cytomegalovirus genotypes in immunocompromised patients on the basis of UL4 gene polymorphisms, Journal of Infectious Diseases, 183(2), 218-225, 2001 Abstract
  • Morris DR, Geballe AP, Upstream open reading frames as regulators of mRNA translation, Molecular and Cellular Biology, 20(23), 8635-42, December 2000 Abstract
  • Landini, M.P., T. Lazzarotto, J. Xu, A.P. Geballe, E.S. Mocarski., Humoral immune response to proteins of human cytomegalovirus latency-associated transcripts, Biology of Blood and Marrow Transplantation, 6, 100-108, 2000
  • Geballe, A.P., M.S. Sachs, eds., N. Sonenberg, J.W.B. Hershey, and M.B. Matthews, Translational control by upstream open reading frames, Translational Control of Gene Expression, 595-614, 2000
  • Alderete JP, Jarrahian S, Geballe AP, Translational effects of mutations and polymorphisms in a repressive upstream open reading frame of the human cytomegalovirus UL4 gene, Journal of Virology, 73(10), 8330-7, October 1999 Abstract
  • Child SJ, Miller MK, Geballe AP, Translational control by an upstream open reading frame in the HER-2/neu transcript, Journal of Biological Chemistry, 274(34), 24335-41, August 1999 Abstract
  • Child SJ, Miller MK, Geballe AP, Cell type-dependent and -independent control of HER-2/neu translation, International Journal of Biochemistry and Cell Biology, 31(1), 201-13, Jan 1999 Abstract
  • Vieira J, Schall TJ, Corey L, Geballe AP, Functional analysis of the human cytomegalovirus US28 gene by insertion mutagenesis with the green fluorescent protein gene, Journal of Virology, 72(10), 8158-65, October 1998 Abstract
  • Cao J, Geballe AP, Ribosomal release without peptidyl tRNA hydrolysis at translation termination in a eukaryotic system, Rna, 4(2), 181-8, February 1998 Abstract
  • Cao J, Geballe AP, Inhibition of nascent-peptide release at translation termination, Molecular and Cellular Biology, 16(12), 7109-14, December 1996 Abstract
  • Harrington RD, Geballe AP, Human immunodeficiency virus type-1 susceptible whole cell and microcell hybrids, Annals of Clinical and Laboratory Science, 26(6), 522-30, 1996 Abstract
  • Cao J, Geballe AP, Coding sequence-dependent ribosomal arrest at termination of translation, Molecular and Cellular Biology, 16(2), 603-8, February 1996 Abstract
  • Cao J, Geballe AP, Translational inhibition by a human cytomegalovirus upstream open reading frame despite inefficient utilization of its AUG codon, Journal of Virology, 69(2), 1030-6, February 1995 Abstract
  • Cao J, Geballe AP, Mutational analysis of the translational signal in the human cytomegalovirus gpUL4 (gp48) transcript leader by retroviral infection, Virology, 205(1), 151-60, November 1994 Abstract
  • Geballe AP, Morris DR, Initiation codons within 5'-leaders of mRNAs as regulators of translation, Trends in Biochemical Sciences, 19(4), 159-64, April 1994 Abstract
  • Harrington RD, Geballe AP, Cofactor requirement for human immunodeficiency virus type 1 entry into a CD4-expressing human cell line, Journal of Virology, 67(10), 5939-47, October 1993 Abstract
  • Degnin CR, Schleiss MR, Cao J, Geballe AP, Translational inhibition mediated by a short upstream open reading frame in the human cytomegalovirus gpUL4 (gp48) transcript, Journal of Virology, 67(9), 5514-21, September 1993 Abstract
  • Yoo BJ, Spaete RR, Geballe AP, Selby M, Houghton M, Han JH, 5' end-dependent translation initiation of hepatitis C viral RNA and the presence of putative positive and negative translational control elements within the 5' untranslated region, Virology, 191(2), 889-99, December 1992 Abstract
  • Geballe AP, Gray MK, Variable inhibition of cell-free translation by HIV-1 transcript leader sequences, Nucleic Acids Research, 20(16), 4291-7, August 1992 Abstract
  • Schleiss MR, Degnin CR, Geballe AP, Translational control of human cytomegalovirus gp48 expression, Journal of Virology, 65(12), 6782-9, December 1991 Abstract
  • Riddell SR, Rabin M, Geballe AP, Britt WJ, Greenberg PD, Class I MHC-restricted cytotoxic T lymphocyte recognition of cells infected with human cytomegalovirus does not require endogenous viral gene expression, Journal of Immunology (baltimore, Md. : 1950), 146(8), 2795-804, April 1991 Abstract
  • Biegalke BJ, Geballe AP, Translational inhibition by cytomegalovirus transcript leaders, Virology, 177(2), 657-67, August 1990 Abstract
  • Geballe AP, Mocarski ES, Translational control of cytomegalovirus gene expression is mediated by upstream AUG codons, Journal of Virology, 62(9), 3334-40, September 1988 Abstract
  • Geballe AP, Spaete RR, Mocarski ES, A cis-acting element within the 5' leader of a cytomegalovirus beta transcript determines kinetic class, Cell, 46(6), 865-72, September 1986 Abstract
  • Geballe AP, Leach FS, Mocarski ES, Regulation of cytomegalovirus late gene expression: gamma genes are controlled by posttranscriptional events, Journal of Virology, 57(3), 864-74, March 1986 Abstract
  • Geballe AP, Ventura P, Stowring L, Haase AT, Quantitative analysis of visna virus replication in vivo, Virology, 141(1), 148-54, February 1985 Abstract
  • Haase AT, Walker D, Stowring L, Ventura P, Geballe A, Blum H, Brahic M, Goldberg R, O'Brien K, Detection of two viral genomes in single cells by double-label hybridization in situ and color microradioautography, Science, 227(4683), 189-92, 1985 Abstract
  • Haase AT, Gantz D, Blum H, Stowring L, Ventura P, Geballe A, Moyer B, Brahic M, Combined macroscopic and microscopic detection of viral genes in tissues, Virology, 140(1), 201-6, 1985 Abstract
  • Higgins NP, Geballe AP, Cozzarelli NR, Addition of oligonucleotides to the 5'-terminus of DNA by T4 RNA ligase, Nucleic Acids Research, 6(3), 1013-24, 1979 Abstract
  • Kreuzer KN, McEntee K, Geballe AP, Cozzarelli NR, Lambda transducing phages for the nalA gene of Escherichia coli and conditional lethal nalA mutations, Molecular & General Genetics : Mgg, 167(2), 129-37, 1978 Abstract
  • Higgins NP, Geballe AP, Snopek TJ, Sugino A, Cozzarelli NR, Bacteriophage T4 RNA ligase: preparation of a physically homogeneous, nuclease-free enzyme from hyperproducing infected cells, Nucleic Acids Research, 4(9), 3175-86, 1977 Abstract

Profile Details

Last Updated: 7/18/2007

COS Expertise ID #135089
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