|Name:||Elizabeth "Lee" Fortunato|
|Credentials:||1995 - PhD., University of California, San Diego|
|Office:||Life Sciences South, Room 147|
My research focuses on host/pathogen interactions of human cytomegalovirus (HCMV). HCMV is a leading cause of birth defects, affecting an estimated 8000 children per year in the US. The deleterious consequences of HCMV congenital infection are as frequent and substantial as other more commonly known birth defects including Down’s Syndrome and Fetal Alcohol Syndrome. Ramifications of HCMV infection are primarily observed in the central nervous system (CNS) and include hearing loss, vision loss, microcephaly and mental retardation. Despite considerable effort, and the magnitude of HCMV infections’ negative consequences, the underlying mechanisms causing these CNS defects remain unknown. The long term goal of our work is to translate the information gained from studying infection in vitro, into understanding the development of CNS defects in congenitally infected infants. Our efforts will contribute to improving the diagnosis and treatment of HCMV affected children and ultimately we hope, to preventing HCMV’s devastating effects.
Our previously funded studies of the host cell DNA and its DNA repair machinery have identified three areas of particular interest that will be pursued in my currently funded NIH-RO! First, HCMV is one of only two viruses known to inflict site-specific chromosomal damage to the host DNA. Fine mapping of the chromosome 1q breaksites has revealed two genes, nidogen 1 (NID2) and myelin protein zero (MPZ), linked to the development of hearing loss in infected infants. Second, studies on DNA repair in HCMV-infected permissive cells found that, although DNA damage responses were activated during infection, they were not completed. Consequently, due to relocalization of components of the repair machinery into viral replication centers, exogenously induced damage was removed preferentially from the viral DNA. We suspect that compromised repair of specific and nonspecific DNA damage may play a role in the development of HCMV-induced birth defects. Third, we are working with a promising new in vitro model, both neonatally derived Neural Progenitor Cells (NPC), and induced pluripotent stem cell (iPSC) derived neural progenitors and neurons. These cells provide a unique opportunity to investigate HCMV infection in a model system directly relevant to the human fetal CNS.
Kulkarni, A.S. and E.A. Fortunato*. 2014. Modulation of homology-directed repair in T98G glioblastoma cells due to interactions between wildtype p53, Rad51 and HCMV IE1-72. Viruses 6(3):968-85.
Duan, Y.L., H.Q. Ye, A.G. Zavala, C.Q. Yang, L.F. Miao, B.S. Fu, K.S. Seao, C. Davrinche, M.H. Luo* and E.A. Fortunato*. 2014. Persistence of high viral genome copies in human cytomegalovirus-infected T98G glioblastoma cells. J. Vrol 88(7):3861-73.
A.G. Zavala, A.S. Kulkarni and E.A. Fortunato*. 2013. Development of a dual-color Southern for the simultaneous analysis of multiple genomes within the same samples. J. of Virol Methods 198:64-8.
O’Dowd, J.M., A.G. Zavala, C. Brown, T. Mori and E.A. Fortunato*. 2012. HCMV-infected cells maintain efficient nucleotide excision repair of the viral genome while abrogating repair of the host genome. PLoS Pathog. 2012 Nov;8(11):e1003038.
Kulkarni, A.S. and E.A. Fortunato (2011). “Stimulation of Homology-directed Repair at I-Scel-induced DNA breaks during the Permissive Life Cycle of Human Cytomegalovirus. J. Virol, 85(12):6049-54.
Luo, M.H., H. Hannemann, et al. (2010). “Human cytomegalovirus infection causes premature and abnormal differentiation of human neural progenitor cells.” J Virol 84(7):3528-3541.
Hannemann, H., K. Rosenke, J.M. O’Dowd, and E.A. Fortunato, The presence of p53 influences the expression of multiple human cytomegalovirus genes at early times postinfection. J Virol, 2009. 83(9): p. 4316-25.
Luo, M.H., P.H. Schwartz, and E.A. Fortunato, Neonatal neural progenitor cells and their neuronal and glial cell derivatives are fully permissive for human cytomegalovirus infection. J Virol, 2008. 82(20): p. 9994-10007.
Nystad, M., T. Fagererheim, V. Brox, E.A. Fortunato, and O. Nilssen, Human cytomegalovirus (HCMV) and hearing impairment: infection of fibroblast cells with HCMV induces chromosome breaks at 1q23.3, between loci DFNA7 and DFNA49—both involved in dominantly inherited, sensorineural, hearing impairment. Mutat Res, 2008. 637(1-2): p. 56-65.
Luo, M.H., K. Rosenke, K. Czornak, and E.A. Fortunato, Human cytomegalovirus disrupts both ataxia telangiectasia mutated protein (ATM)- and ATM-Rad3-related kinase-mediated DNA damage responses during lytic infection. J. Virol, 2007. 81(4): p. 1934-50.