Adam Geballe
Adjunt Professor of Microbiology
Professor of Medicine
Member, Fred Hutchinson Cancer Research Center

COS Profile
Email: ageballe@fred.fhcrc.org
Phone:(206) 667-5122, (206) 667-5199
Office Location: Fred Hutchinson Cancer Research Center
Campus Box: 358080

Research:

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), 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 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 proteins also self-associate and cause PKR relocalization to the nucleus, an unusual effect among viral anti-PKR protein. A related virus, Mouse CMV, has genes of similar function and comparisons between the human and mouse viruses are proving 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.

Selected Publications:

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).