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Investigators and Program Directors

Robert L. Glaser

Robert L. Glaser

Research Scientist, Wadsworth Center, Molecular Genetics
Assistant Professor,School of Public Health, Viral Replication and Vector Biology

Ph.D., Cornell University (1989)
Postdoctoral training, Carnegie Institution of Washington


Research Interests

Host:Arbovirus Interactions

Human diseases caused by arboviruses are a significant source of human morbidity and mortality worldwide, and are also a chronic and emerging threat in temperate regions, as illustrated by the recent establishment and spread of West Nile virus in North America. Little is known about the genes that modulate infection in the normal enzootic hosts of arboviruses despite the recognized importance of host genetics as a determinant of susceptibility. We have established a robust genetic system involving West Nile virus infection of the fruit fly Drosophila melanogaster to identify host genes that modulate infection. We have demonstrated, for example, that the RNA interference pathway provides innate immunity against West Nile virus infection in flies. We are using a variety of large-scale, functional genetic screens in D. melanogaster to identify host genes that are important for arbovirus infection of flies. Observations made using D. melanogaster then provide an empirically based starting point for investigating arbovirus infection of mosquitoes that are the natural vectors of human disease.

Batten Disease

Neuronal ceroid lipofuscinoses (NCLs), commonly referred to as Batten Disease, are a group of fatal genetic neurodegenerative diseases characterized by the progressive death of CNS neurons. The molecular pathology of NCLs is not known, but likely involves disruption of normal lysosome function. Infantile NCL, the most severe form of NCL, is caused by mutations in the Ppt1 gene, which encodes the lysosomal enzyme palmitoyl-protein thioesterase 1. We are investigating the function of the Ppt1 ortholog in the fruit fly Drosophila melanogaster. To that end, we have generated mutations in the fly Ppt1 gene and demonstrated that Ppt1-deficient flies accumulate abnormal autofluorescent storage material in CNS neurons and have a shortened lifespan, phenotypes seen in human NCL disease. Having a genetically tractable model system to study INCL provides opportunities to elucidate the molecular iteology of disease.

Chromatin Structure

Histone variants are unique, single-copy histones that provide specialized functions within chromatin. We are studying functions of the H2AZ and H2AX families of histone variants, which have roles in transcription and DNA repair, respectively. In Drosophila melanogaster, both H2AZ and H2AX functions are provided by the chimeric histone variant H2Av. We are using genetic, biochemical, and cytological techniques to elucidate the functions of H2Av in transcription and DNA repair.

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