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Sexually transmitted diseases
Dr. Manoj Pastey
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.
Professional and Research Interests:
- Pathogenesis of herpes virus infected animal disease
- Host and virus interaction in central nervous system
- Mechanism of herpes virus latency-reactivation cycles
- Anti-viral drug development
Interactions Between Chlamydiae and The Mammalian Host.
The four species of chlamydiae are obligate intracellular bacteria that cause disease in a wide variety of animal species. In humans, Chlamydia trachomatis and C. pneumoniae cause a variety of diseases of the eye, genital tract and lung. These conditions affect millions of people worldwide and lead to billions of dollars in medical expenses yearly in the U.S. alone. Additionally, chlamydial etiology has been postulated for certain types of arthritis and, most surprisingly, arterial sclerosis. Although the host range and diseases caused by the chlamydiae are diverse, the infectious process used by all chlamydiae is very similar. All chlamydiae have an alternating life cycle consisting of two distinct developmental forms. Attachment to and entry into the host cell is mediated through a non-metabolic life stage, the elementary body (EB), while intracellular multiplication progresses through the reticulate body (RB), a metabolically active, non-infectious form. After EB attachment and entry, chlamydiae remain separated from the cytoplasm in a membrane-bound vesicle, which grows in size until cell lysis and bacterial release. Fusion of the inclusion with host cell lysosomes is specifically inhibited during infection by chlamydiae- a process that protects the invading bacterium from the toxic environment within the lysosome. Conversely, fusion of the inclusion with Golgi derived vesicles is an integral part of the developmental process and it is thought this pathway may deliver nutrients to the growing chlamydiae. A final twist in this story is that early chlamydial protein synthesis is required for the placement of the inclusion into the appropriate vesicle trafficking pathway. Very little is known of the molecular events leading to these processes.
Our laboratory group focuses on mechanisms used by chlamydiae to develop and maintain the inclusion. We (and others) have identified a collection of proteins- termed Inc proteins- that are localized to the inclusion membrane of infected cells. Each of these proteins is present in Chlamydia -infected tissue culture cells but absent in the purified elementary bodies. Additionally, IncA is exposed to the cytoplasm of infected cells and is phosphorylated by host cell protein kinases. These data are exciting because they show Inc proteins to be potentially very important in the unique interactions between host cells and chlamydiae. We hope to use these lines of investigation to further our understanding of the cellular processes parasitized by chlamydiae during infection, and possibly to identify ways to interfere with this parasitism.
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