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Sharma, Tanvi

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Sharma

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Tanvi

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Sharma, Tanvi
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    CD8+ T-Cell Interleukin-7 Receptor Alpha Expression as a Potential Indicator of Disease Status in HIV-Infected Children
    (Public Library of Science, 2008) Sharma, Tanvi; Hughes, Jane; Murillo, Amarylis; Riley, Joanne; Soares, Andreia; Little, Francesca; Mitchell, Charles D.; Hanekom, Willem A.
    Background: Initiation and modification of antiretroviral therapy in HIV-infected children depend on viral load and CD4+ T-cell count. However, these surrogates have limitations, and complementary immunological markers to assess therapeutic response are needed. Our aim was to evaluate CD8+ T-cell expression of CD127 as a marker of disease status in HIV-infected children, based on adult data suggesting its usefulness. We hypothesized that CD127 expression on CD8+ T-cells is lower in children with more advanced disease. Methods: In a cross-sectional evaluation, we used flow cytometry to measure CD127+ expression on CD8+ T-cells in whole blood from HIV-infected children with varying disease status. This was compared with expression of CD38 on this subset, currently used in clinical practice as a marker of disease status. Results: 51 HIV-infected children were enrolled. There was a strong positive correlation between CD127 expression on CD8+ T-cells and CD4+ T-cell count, and height and weight z-scores, and a strong negative correlation between CD127 expression and viral load. In contrast, we found no association between CD38 expression and these disease status markers. Conclusions: CD8+ T-cell CD127 expression is significantly higher in children with better HIV disease control, and may have a role as an immunologic indicator of disease status. Longitudinal studies are needed to determine the utility of this marker as a potential indicator of HIV disease progression.
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    Resolving Medulloblastoma Cellular Architecture by Single-Cell Genomics
    (Springer Science and Business Media LLC, 2019-07-24) Hovestadt, Volker; Goumnerova, Liliana; Sharma, Tanvi; Rusert, Jessica M.; Wechsler-Reya, Robert J.; Li, Xiao-Nan; Peyrl, Andreas; Gojo, Johannes; Kirchhofer, Dominik; Lötsch, Daniela; Czech, Thomas; Dorfer, Christian; Haberler, Christine; Geyeregger, Rene; Halfmann, Angela; Gawad, Charles; Easton, John; Pfister, Stefan M.; Gajjar, Amar; Orr, Brent A.; Slavc, Irene; Robinson, Giles W.; Northcott, Paul A.; Smith, Kyle; Bihannic, Laure; Filbin, Mariella; Shaw, McKenzie; Baumgartner, Alicia; DeWitt, John; Groves, Andrew; Mayr, Lisa; Weisman, Hannah; Richman, Alyssa; Shore, Marni; Carter, Robert; Phoenix, Timothy; Hadley, Jennifer; Tong, Yiai; Rivera, Miguel; Suva, Mario; Houston, Jim; Ashmun, Richard; DeCuypere, Michael; Flasch, Diane; Silkov, Antonina; Bernstein, Bradley; Ligon, Keith; Rozenblatt-Rosen, Orit; Regev, Aviv; Pomeroy, Scott; Rosencrance, Celeste
    Medulloblastoma is a malignant childhood cerebellar tumour comprised of distinct molecular subgroups. Whereas genomic characteristics of these subgroups are well defined, the extent to which cellular diversity underlies their divergent biology and clinical behaviour remains largely unexplored. We used single-cell transcriptomics to investigate intra- and inter-tumoural heterogeneity in twenty-five medulloblastomas spanning all molecular subgroups. WNT, SHH, and Group 3 tumours comprised subgroup-specific undifferentiated and differentiated neuronal-like malignant populations, whereas Group 4 tumours were exclusively comprised of differentiated neuronal-like neoplastic cells. SHH tumours closely resembled granule neurons of varying differentiation states that correlated with patient age. Group 3 and Group 4 tumours exhibited a developmental trajectory from primitive progenitor-like to more mature neuronal-like cells, whose relative proportions distinguished these subgroups. Cross-species transcriptomics defined distinct glutamatergic populations as putative cells-of-origin for SHH and Group 4 subtypes. Collectively, these data provide novel insights into the cellular and developmental states underlying subtype-specific medulloblastoma biology.