Adjunt Professor of Microbiology
Professor of Medicine
Member, Fred Hutchinson Cancer Research Center
Phone:(206) 667-5122, (206) 667-5199
Office Location: Fred Hutchinson Cancer Research Center
Campus Box: 358080
Adam P. Geballe received a B.A. degree from Stanford University before completing the M.D. degree at Duke University. He completed postgraduate training in internal medicine, infectious diseases and medical microbiology prior to joining the scientific staff of the Fred Hutchinson Cancer Research Center where he is now a Member. In addition to his faculty appointment in the Department of Microbiology, Dr. Geballe is a Professor of Medicine.
Human cytomegalovirus (HCMV) causes substantial morbidity and mortality, primarily in newborns and immunocompromised patients. Like other viruses, HCMV must evade myriad host cell antiviral defense mechanisms, among which is the shut off of overall protein synthesis mediated by the interferon-induced, double-stranded RNA (dsRNA)-activated protein kinase R (PKR). HCMV encodes two proteins, pTRS1 and pIRS1, that block PKR activation. Investigations of this effect have revealed that these viral proteins self-associate, bind to dsRNA and to PKR, and cause PKR to relocalize to the nucleus. As well, either of the two proteins is necessary for viral replication. Current research in the Geballe lab aims to elucidate the detailed molecular interactions between pTRS1 and its binding partners PKR and dsRNA. Additional experiments are underway to identify and determine the mechanism of analogous dsRNA binding proteins encoded by related CMVs of primates and rodents. Another line of research aims to identify the genes and mechanisms by which poxviruses evade PKR and other host dsRNA-activated anti-viral pathways. These studies should reveal new insights into the host-virus interactions that are likely to be key determinants of the pathogenesis of viral infections and may have implications for the design of viral vaccines and vectors.
Hakki, M. and A. P. Geballe. 2005. Double-stranded RNA binding by human cytomegalovirus pTRS1. J. Virol. 79:7311-7318.
Sachs, M.S. and A.P. Geballe. 2006. Downstream control of upstream open reading frames. Genes and Development. 20:915-921.
Child, S.J., L.K. Hanson, C.E. Brown, D.M. Janzen, and A.P. Geballe. 2006. Double-stranded RNA-binding by a heterodimeric complex of murine cytomegalovirus m142 and m143 proteins. J. Virol. 80:10173-10180.
Spevak, C.C., E.-H. Park, A.P. Geballe, J. Pelletier, and M.S. Sachs. 2006. Her-2 upstream open reading frame effects on the use of downstream initiation codons. BBRC. 350:834-841.
Hakki, M., E. Marshall, K De Niro, and A.P. Geballe. 2006. Binding and nuclear relocalization of PKR by human cytomegalovirus TRS1. J. Virol. 80:11817-11826.
Zager, RA, A.C.M Johnson, and A. Geballe. 2007. Gentamicin suppresses TNF production in human and mouse proximal tubule cells. Am. J. Physiol. Renal Physiol. 293:F1373-80.
Hakki, M. and A.P. Geballe. 2008. Cytomegalovirus. p439-451. In: Holmes, K.K., P.F. Sparling, W.E. Stamm, P. Piot, J.N. Wasserheit, L. Corey, M.S. Cohen, and D.H. Watts, eds. Sexually Transmitted Diseases, 4th Edition, McGraw-Hill.
Hakki, M. and A.P. Geballe. 2008. Cellular serine/threonine phosphatase activity during human cytomegalovirus infection. Virology (in press).
Elde, N, S.J. Child, A.P. Geballe, and H.S. Malik. 2009. Protein kinase R reveals an evolutionary model for defeating viral mimicry. Nature 457:485-489. PMC2629804
Child, S.J and A.P. Geballe. 2009. Binding and relocalization of protein kinase R by murine cytomegalovirus. J. Virol. 83:1790-1799. PMC2643750.
Marshall, E.E., C.J. Bierle, W. Brune, and A. P. Geballe. 2009. Essential role for either TRS1 or IRS1 in human cytomegalovirus replication. J. Virol. 83:4112-4120. PMC2668495.
Marshall, E.E. and A.P. Geballe. 2009. Multifaceted evasion of the interferon response by cytomegalovirus. J. Interferon Cytokine Res. 29:1-11. PMC2743745.
Strang, B.L., A.P. Geballe, and D.M. Coen. 2010. Association of human cytomegalovirus proteins IRS1 and TRS1 with the viral DNA polymerase accessory subunit UL44. J. Gen Virology, 91:2167-2175. PMID: 20444996
Boeckh, M. and A.P. Geballe. 2011. Cytomegalovirus – Pathogen, Paradigm and Puzzle, J. Clin. Invest. 121:1673-1680. PMID: 21659716
Gantt, S., J. Carlsson, M. Ikoma, E. Gachelet, M Gray, A.P. Geballe, L. Corey, C. Casper, M. Lagunoff, and J. Vieira. 2011. The HIV-1 protease inhibitor nelfinavir inhibits Kaposi sarcoma-associated herpesvirus replication in vitro. Antimicrobial Agents and Chemotherapy. 56:2696-2703. PMID: 21402841