Donald H. Gilden

Professor M.D., University of Maryland School of Medicine

Current Research

There are two main thrusts to our laboratory efforts. First is the study of varicella-zoster virus (VZV) latency in the human nervous system. Our analysis of ganglia removed at autopsy has shown that during latency, VZV DNA can be detected at a frequency of 6 to 30 copies per 100,000 cells. Further, the complete virus DNA molecule is present in an episomal form at all levels of the neuraxis. We have recently determined that in latently infected ganglia, VZV transcription is limited to a subset of virus genes normally transcribed during lytic growth, and have for the first time, identified a VZV gene product in latently infected human ganglia. Our ongoing characterization of VZV latency includes determining the human ganglionic cell type which harbors VZV during latency, and the role of VZV gene regulation in maintaining latency.
A second important project uses a molecular approach to understand and define humoral responses in multiple sclerosis (MS). The goals of this work are to identify an antigen or sequences unique to MS. mRNA isolated from plaque-periplaque white matter is used to construct directional cDNA expression libraries. cDNA libraries are subtracted by hybridization to normal white matter mRNA and differentially screened to identify unique MS transcript, and screened with oligoclonal IgG present in MS CSF to identify MS-specific antigens. In addition, cDNA libraries will be used to amplify, clone and sequence IgG heavy and light chains expressed in MS plaque-periplaque white matter. This characterization of the IgG repertoire found in MS brain will allow potential disease-relevant sequences to be identified. Recombinant antibodies prepared from these heavy and light chain variable regions will then be analyzed for specific binding to antigens in MS brain and used to screen MS cDNA libraries.

Recent Publications

Click Here For An Updated List Of Dr. Gilden's Publications

Owens, G.P., Ritchie, A.M., Gilden, D.H., Burgoon, M.P., Becker, D., Bennett, J.L.: Measles virus-specific plasma cells are prominent in SSPE CSF. Neurology 68:1815-1819, 2007.

Nagel, M.A., Gilden, D.H.: The protean neurologic manifestations of varicella zoster virus infection. Cleve. Clin. J. Med. 74:489-504, 2007.

Orme, H.T., Smith, G., Nagel, M.A., Bert, R.J., Mickelson, T.S., Gilden, D.H.: VZV spinal cord infarction identified by diffusion-weighted MRI (DWI). Neurology 69:398-400, 2007.

Yu, X., Burgoon, M.P., Shearer, A.J., Gilden, D.H.: Characterization of phage peptide interaction with antibody using phage mediated immuno-PCR. J. Immunol. Methods 325:33-40, 2007.

Kolappaswamy, K., Mahalingam, R., Traina-Dorge, V., Shipley, S.T., Gilden, D.H., Kleinschmidt-DeMasters, B.K., McLeod, C.G., Jr., Hungerford, L.L., DeTolla, L.J.: Disseminated SVV in an irradiated rhesus macaque (Macaca mulatta). J. Virol. 81:411-415, 2007.

Gilden, D.H., Mahalingam, R., Cohrs, R.J., Tyler, K.L.: Herpesvirus infections of the nervous system. Nature Clin. Pract. Neurol. 3:82-94, 2007.

Nagel, M.A., Forghani, B., Mahalingam, R., Wellish, M.C., Cohrs, R.J., Russman, A.N., Katzan, I., Lin, R., Gardner, C.J., Gilden, D.H.: The value of detecting anti-VZV IgG antibody in CSF to diagnose VZV vasculopathy. Neurology 68:1069-1073, 2007.

Cohrs, R.J., Gilden, D.H.: Prevalence and abundance of latently transcribed VZV genes in human ganglia. J. Virol. 81:2950-2956, 2007.

Mahalingam, R., Gilden, D.H., Wellish, M., Pugazhenthi, S.: Transactivation of the simian varicella virus (SVV) open reading frame (ORF) 21 promoter by SVV ORF 62 is upregulated in neuronal cells, but downregulated in non-neuronal cells by SVV ORF 63 protein. Virology 345:244-250, 2006.

Hoover, S.E., Cohrs, R.J., Rangel, Z.G., Gilden, D.H., Munson, P., Cohen, J.I.: Downregulation of varicella zoster virus (VZV) immediate-early ORF62 transcription by VZV ORF63 correlates with virus replication in vitro and with latency. J. Virol. 80:3459-3468, 2006.

Cohrs, R.J., Gilden, D.H., Gomi, Y., Yamanishi, K., Cohen, J.I.: Comparison of virus transcription during lytic infection of the Oka parental and vaccine strains of VZV. J. Virol. 80:2076-2082, 2006.

Owens, G.P., Bennett, J.L., Gilden, D.H., Burgoon, M.P.: The B cell response in multiple sclerosis. Neurol. Res. 28:236-244, 2006.

Gary, L., Gilden, D.H., Cohrs, R.J.: Epigenetic regulation of VZV ORF 62 and 63 in latently infected human trigeminal ganglia. J. Virol. 80:4921-4926, 2006.

Yu, X., Gilden, D.H., Ritchie, A.M., Burgoon, M.P., Keays, K.M., Owens, G.P.: Specificity of recombinant antibodies generated from multiple sclerosis cerebrospinal fluid probed with a random peptide library. J. Neuroimmunol. 172:121-131, 2006.

Yu, X., Owens, G.P., Gilden, D.H.: Rapid and efficient identification of epitopes/mimotopes from random peptide libraries. J. Immunol. Methods 316:67-74, 2006.

Moses, H., Nagel, M.A., Gilden, D.H.: Acute cerebellar ataxia in a 41-year-old woman. Lancet Neurol. 5:984-988, 2006.

Burgoon, M.P., Caldas, Y.A., Keays, K.M., Yu, X., Gilden, D.H., Owens, G.P.: Recombinant antibodies generated from both clonal and less abundant plasma cell IgG sequences in SSPE brain are directed against measles virus. J. NeuroVirol. 12:398-402, 2006.

Owens, G.P., Shearer, A.J., Yu, X., Ritchie, A.M., Keays, K.M., Bennett, J.L., Gilden, D.H., Burgoon, M.P.: Screening random peptide libraries with subacute sclerosing panencephalitis brain-derived recombinant antibodies identifies multiple epitopes in the C-terminal region of the measles virus nucleocapsid protein. J. Virol. 80:12121-12130, 2006.