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Oregon State University College of Veterinary Medicine eNewsletter

Research Profile- Dr. Manoj Pastey

March 29th, 2010
Dr. Manoj Pastey

Dr. Manoj Pastey

Dr. Manoj Pastey completed his veterinary degree program in India in 1988 and joined University of Maryland, College Park, for MS and PhD degree programs. In 1997, he joined Vanderbilt University Medical Center as a post doctoral fellow.  In 2001, Pastey worked as a staff scientist at Vaccine Research Center, National Institutes of Health, Bethesda, before he joined the Department of Biomedical Science, College of Veterinary Medicine, Oregon State University as an assistant professor in 2004.

Dr. Manoj Pastey’s laboratory is conducting research work on the pathogenesis of influenza, HIV, and respiratory syncytial virus (RSV).

Proteomics– Each sample that was run on a 2-D gel was labeled with a fluorescent dye. Once each gel is imaged at the different wavelengths; the overlay of those images can then be used to see where the expression is differential. The identical protein between groups can be seen in yellow where as differentially expressed proteins appear in red/green. Left: Coinfection with S. aureus and influenza. Right: S. aureus infection with uninfected control.

Influenza Research Study: Each year, influenza kills approximately 36,000 people in the United States. These deaths are mainly due to secondary bacterial infection. Therefore, we are focusing our research on identifying biomarkers in blood and urine for respiratory tract dysfunction caused by co-infection of Staphylococcus aureus and influenza virus. Accomplishments of the proposed goals will help us predict the evolution of S. aureus super-infection in patients with H1N1 influenza virus disease.  Using mice co-infected with influenza virus and S. aureus, gene expression changes obtained from DNA-microarrays and proteomic changes obtained from mass spectrometry will aid in identification of early and clinically relevant diagnostic and prognostic bio-markers.  This knowledge will allow development of a predictive statistical model to afford a better understanding of virulence mechanisms and pathogenesis of respiratory tract co-infections by these microorganisms, such that risk of pneumonia can be assessed and effective preventative or treatment regimens can be initiated in infected individuals.

HIV Research Study: Our laboratory is testing a polyherbal vaginal microbicide named “BASANT” that has been shown to inhibit a wide range of sexually transmitted pathogens including HIV. Preliminary studies have also shown safety and acceptability in Phase I (acceptability and toxicity study) human trials in India.  Therefore, the next step is to verify the effectiveness of the BASANT in preventing HIV transmission in vivo. The central goal of these studies is to understand the mechanism of microbicide anti-HIV action and to determine the efficacy of BASANT in preventing intravaginal/intrarectal HIV transmission in humanized mouse model. In addition, the efficacy of BASANT will be evaluated against six major globally prevalent strains of genetically and biologically characterized HIV-1 isolates.

Colocalization of RSV M and AP3M1, post 24 hours. Upper left: DAPI. Upper center: Ap3m1. Upper right: RSV Matrix. Bottom left: Merge.

RSV Research Study: Respiratory Syncytial Virus (RSV) is a leading cause of bronchopneumonia in infants and the elderly. There are no vaccines or effective treatment available. Knowledge of viral and host protein interactions is important for better understanding of the viral pathogenesis and may lead to development of novel therapeutic drugs. In our lab, we have shown that Respiratory Syncytial Virus Matrix (M) protein interacts with cellular adaptor protein complex (AP)-3 and its medium (µ) subunit. A yeast two-hybrid assay indicated a novel protein-protein interaction that was then further confirmed in a mammalian system by co-localization between the RSV M and AP3 µ 1 proteins in a cytoplasmic defined region via Confocal Laser Scanning Microscopy (CLSM) analysis. Further evidence of this novel interaction was indicated via the presence of a known adaptor protein µ subunit sorting signal sequence, YXXL that is conserved across various animal RSV M proteins. Subsequent Western blot studies also showed a specific upregulation in the amount of AP3 µ 1 protein found in the cell during RSV infection, while corresponding subunits of the AP3 complex were unaffected. The interaction of AP3 µ 1 with RSV M represents a critical insight into the life cycle of this important virus and may represent a novel drug target.

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