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| Eugene O. Major, Ph.D., Senior Investigator |
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Dr. Major received his A.B. 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 basic research laboratory focusing on mechanisms of viral pathogenesis in the human nervous system, which includes JC Virus-induced demyelination, Progressive Multifocal Leukoencephalopathy, and HIV-1 associated encephalopathy. As Chief of the Laboratory of Molecular Medicine and Neuroscience, Dr. Major�s investigations focus on the biology of virus infections in nervous system cells derived from human brain and the molecular regulation which controls cellular and viral gene expression.
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Staff:
- Karen Augustine, Office Manager, (301) 594-6270 augustink@ninds.nih.gov
- Blanche Curfman, B.S., Biologist, (301) 496-2043 curfmanb@ninds.nih.gov
- Linda Durham, M.Sc, Microbiologist, (301) 496-5691 durhaml@ninds.nih.gov
- Jean Hou, B.S., Biologist, (301) 435-6834 houj@ninds.nih.gov
- Peter Jensen, B.S., Biologist, (301) 496-2899 jensenp@ninds.nih.gov
- Diane Lawrence, Ph.D., Special Volunteer, (301) 402-3605 lawrencedi@nida.nih.gov
- Chiara Monaco-Kushner, Ph.D., Staff Scientist, (301) 496-1806 monaco@ninds.nih.gov
- Andre Phillips, M.Sc, Special Volunteer, (301) 402-3605 phillipsa@ninds.nih.gov
- Veerasamy Ravichandran, Ph.D., Contractor, (301) 594-3248 ravichanr@ninds.nih.gov
- Caroline Ryschkewitsch, B.S., Medical Technologist ryschkec@ninds.nih.gov
- Bruce Sabath, B.S., Special Volunteer, (301) 402-3605 Bruce@jhmi.edu
- Lynnae Schwartz, M.D., Senior Research Fellow, (301) 594-3226 schwartzl@ninds.nih.gov
Research Interests:
Investigators study viral infections of the human 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 immune compromised individuals, particularly with AIDS. An estimated 4-6% of all AIDS cases will develop PML, which in many cases has been the AIDS defining illness. Similarly, HIV-1 infection of the CNS also casues encephalopathy with mild or severe neurologic impairments, termed AIDS dementia complex (ADC). Clinical symptoms and pathology of ADC may resemble that seen in PML
JCV or HIV pathogenesis is most commonly studied in cell cultures derived from human fetal brain (HFB). In vitro, JCV robustly infects astrocytes, the most abundant cell type, while HIV-1 infects astrocytes latently. As such, it has been important to identify the cellular phenotypes in the HFB cultures. The lab has recently produced a human-nestin specific antibody which 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 the selective cell-type tropism of JCV. Future studies will involve the cellular mechanisms controlling viral susceptibility as well as the characterization of these cells during CNS development
As a CLIA certified laboratory, this section also tests clinical samples for the presence of JCV, BKV, and SV40. The Viral Diagnostic Group has developed the molecular technology for the ultransensitive 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 viral DNA sequences in various tissues, including tumor tissue
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Selected Recent Publications:
Messam CA, Hou J, Gronostajski RM, Major EO. (2003) Lineage pathway of human brain progenitor cells identified by JC virus susceptability, Annals of Neurology.
Full Text/Abstract
Monaco MC, Sabath BF, Durham LC, Major EO. (2001) JC virus multiplication in human hematopoietic progenitor cells requires the NF-1 class D transcription, Journal of Virology 75(20), 9687-95.
Full Text/Abstract
Major E.O. (2001) Human Polyomaviruses, Fields Virology Fourth Edition, 2141.
All Selected Publications
Contact Information:
Dr. Eugene O. Major
Laboratory of Molecular Medicine and Neuroscience, NINDS
Building 10, Room 3B14
10 Center Drive, MSC 1296
Bethesda, MD 20892-1296
Telephone: (301) 594-6270 (office),
(301) 496-2043 (laboratory),
(301) 594-5799 (fax)
Email: MajorG@ninds.nih.gov
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