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High-probability grants
According to our matching algorithm, Jia Zhu is the likely recipient of the following grants.
Years |
Recipients |
Code |
Title / Keywords |
Matching score |
2012 — 2016 |
Corey, Lawrence [⬀] Zhu, Jia |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Cytotoxic T-Cell Responses to Hsv in Hiv-Infected Persons @ Fred Hutchinson Cancer Research Center
DESCRIPTION (provided by applicant): In the past grant period, we have shown that HSV-2 specific CD8+ T cells reside and persist at the dermal-epidermal junction (DEJ) contiguous to the sensory nerve termini innervating the basal keratinocytes of the genital skin. Using laser capture microdissection we have isolated single CD8+ DEJ T cells in situ and interrogating these cells with transcriptional arrays and quantitative RT PCR assays. Our data indicates these cells express a wide variety of cytolytic and antiviral cytokines, as well as a unique homodimeric ?? chain signature. We have also developed rigorous and specific sampling methods to precisely pinpoint the sites of HSV-2 reactivation in the genitalia in time and space. Our preliminary data have shown wide differences in the number of CD8+ DEJ T cells in areas of genital skin. We now propose to apply these and other advanced methodologies to understand the immune surveillance mechanism of HSV-2 specific CD8+ T cells. Specifically, in Aim 1 we will probe the relationship between immunosurveillance and duration, severity, and frequency of HSV-2 reactivation. We hypothesize that the number of CD8+ T cells and/or their levels of expression of cytolytic and antiviral cytokines/chemokines will be inversely correlated with frequency of HSV-2 reactivation. Areas in which DEJ CD8+ T cells are in low numbers or express low functional activity will have a greater likelihood of reactivation than areas which are populated with high CD8+ T cells at the DEJ. We will also explore the relationships between clonal diversity and reactivation. Aim 2 is directed at defining host-viral interactions among HIV+ persons. We hypothesize that HIV+ persons will exhibit altered quantitative and functional differences in immune surveillance and that these differences will be reflected in poorer containment of HSV-2. The comparisons between HIV+/HSV-2+ and HIV-/HSV-2+ persons will provide further evidence of the importance of CD8+ T cells at the DEJ in immune surveillance and corroborate the mechanistic functions define in S.A. 1.
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0.918 |