Laboratory of Molecular Medicine and Neuroscience - Division of Intramural Research
Eugene O. Major, Ph.D., Senior Investigator
Dr. Major received his B.A. degree from Holy Cross College and his M.S. and Ph.D. degrees from the University of Illinois Medical Center. Following academic appointments as Associate Professor at the University of Illinois Medical School and the Loyola University Medical School in Chicago and Associate Dean of Graduate Programs at Loyola, Dr. Major joined the Neurology Institute at the NIH in 1981. He has developed a translational research laboratory focusing on mechanisms of viral pathogenesis in the human nervous system, which includes JC virus-induced demyelination, progressive multifocal leukeoencephalopathy, and HIV-1 induced associated encephalopathy. As Chief of the Laboratory of Molecular Medicine and Neuroscience, Dr. Major's investigations focus on the biology of the virus infections in nervous system cells derived from human brain and the molecular regulation, which controls cellular and viral gene expression.
, M.Sc, Microbiologist
, Ph.D., Post-Doctoral IRTA
, B.S., Biologist
, Ph.D., Contract Scientist
, Ph.D., Research Fellow
, Ph.D., Staff Scientist
, B.S., Medical Technologist
Investigators study viral infections of the human central nervous system (CNS), concentrating on virus-cell interactions and the molecular regulation of viral susceptibility. Infection with the neurotropic viruses JCV and HIV-1 can result in white matter diseases of the brain, although both viruses also infect immune cells. Lytic JCV infection of oligodendrocytes causes the fatal demyelinating disease Progressive Multifocal Leukoencephalopathy (PML), which occurs almost exclusively in immunocompromised individuals. Recently, immunomodulatory therapies such as natalizumab show an increased risk of PML compared with other immune-altering treatments with an approximate incidence rate of 1/1000.
JCV or HIV pathogenesis is the most commonly studied in cell cultures derived from human fetal brain (HFB). In vitro, JCV robustly infects astrocytes, the most abundant cell types, while HIV-1 infects astrocytes latently. As such, it has been important to identify the cellular phenotypes in the HFB cultures. The lab produced a human-nestin specific antibody that identifies progenitor cells in the developing human brain. Using this antibody, the development and differentiation of human progenitor cells into neurons or astrocytes has been studied, along with selective cell-type trophism of JCV. This knowledge will yield valuable information about viral susceptibility of cells as well as their characteristics during CNS development.
As a CLIA certified laboratory, this section also tests clinical samples for the presence of JCV, BKV, and SV40. The Viral Analysis Unit, headed by Caroline Rsychkewitsch, has developed the molecular technology for the ultrasensitive detection of viral genomes and antibodies to human polyomaviruses and SV40. The standardized and validated techniques are currently being utilized in collaborative studies examining the incidence of polyomavirus infection in the human population, as well as the presence of the viral DNA sequences in various tissues, including tumor tissues.
NIH Sample Form
Collection & Shipping Criteria
PML Protocol Announcement
Selected Recent Publications
Monaco MC, Major EO
The link between VLA-4 and JC virus reactivation Expert Rev, Clin Immunol, 2012, vol. 8 (1), pp. 63-72.
Major, EO, Nath A.
Neurological infections: risks of globalisation and new drugs, Lancet Neurol, 2012, vol. 11 (1), pp. 14-5.
Marshall LJ, Moore, LD, Mirsky MM, Major EO
JC virus promoter/enhancers contain TATA box associated with Spi-B binding sites that support early viral gene expression in primary astrocytes, J Gen Virol, 2011
W, Henderson LJ, Major EO, Al-Harthi L
IFN-gamma mediates enhancement of HIV replication in astrocytes by inducing an antagonist of the beta-catenin pathoway (DKK1) in a STAT 3-dependent manner, J Immunol, 2011, vol. 186 (12), pp. 6771-8.
Jiang, Z.G., Cohen, J., Marshall, L.J., and Major, E.O
Hexadecyloxypropyl-cidofovir (CMX001) suppresses JC virus replication in human fetal brain SVG cell cultures, Antimicrob Agents Chemother, 2010, vol. 54, pp. 4723-32.
Marshall, L J. , Dunham, L.D., Major, E.O
The transcription factor Spi-B binds unique sequence present in the tandem repeat promoter/enhancer of JC virus and support viral activity, J Gen Virol, 2010, vol. 91, pp. 3042-3052.
Ryschewitsch, C.F., Jensen, P.N., Monaco, M.C., Major, E.O
JC virus persistence following progressive multifocal Leukoencephalopathy in multiple sclerosis patients treated with Natalizumab, Annals of Neurology, 2010, vol. 68, pp. 384-391.
Gosert, R., Kardas, P., Major, E.O., Hirsch, H.H
Rearranged JC Virus Noncoding Control Regions Found in Progressive Multifocal Leukoencephalopathy Patient Samples Increase Virus Early Gene Expression and Replication Rate, J. of Virology, 2010, vol. 84, pp. 10448-10456.
Selected Earlier Publications