Browsing by Author "Banerjee, Pinaki P."

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    Cancer-associated rs6983267 SNP and its accompanying long noncoding RNA CCAT2 induce myeloid malignancies via unique SNP-specific RNA mutations
    (Cold Spring Harbor Laboratory Press, 2018-04) Shah, Maitri Y.; Ferracin, Manuela; Pileczki, Valentina; Chen, Baoqing; Redis, Roxana; Fabris, Linda; Zhang, Xinna; Ivan, Cristina; Shimizu, Masayoshi; Rodriguez-Aguayo, Cristian; Dragomir, Mihnea; Van Roosbroeck, Katrien; Almeida, Maria Ines; Ciccone, Maria; Nedelcu, Daniela; Cortez, Maria Angelica; Manshouri, Taghi; Calin, Steliana; Muftuoglu, Muharrem; Banerjee, Pinaki P.; Badiwi, Mustafa H.; Parker-Thornburg, Jan; Multani, Asha; Welsh, James William; Estecio, Marcos Roberto; Ling, Hui; Tomuleasa, Ciprian; Dima, Delia; Yang, Hui; Alvarez, Hector; You, M. James; Radovich, Milan; Shpall, Elizabeth; Fabbri, Muller; Rezvani, Katy; Girnita, Leonard; Berindan-Neagoe, Ioana; Maitra, Anirban; Verstovsek, Srdan; Foddle, Riccardo; Bueso-Ramos, Carlos; Gagea, Mihai; Manero, Guillermo Garcia; Calin, Goerge A.; BioHealth Informatics, School of Informatics and Computing
    The cancer-risk-associated rs6983267 single nucleotide polymorphism (SNP) and the accompanying long noncoding RNA CCAT2 in the highly amplified 8q24.21 region have been implicated in cancer predisposition, although causality has not been established. Here, using allele-specific CCAT2 transgenic mice, we demonstrate that CCAT2 overexpression leads to spontaneous myeloid malignancies. We further identified that CCAT2 is overexpressed in bone marrow and peripheral blood of myelodysplastic/myeloproliferative neoplasms (MDS/MPN) patients. CCAT2 induces global deregulation of gene expression by down-regulating EZH2 in vitro and in vivo in an allele-specific manner. We also identified a novel non-APOBEC, non-ADAR, RNA editing at the SNP locus in MDS/MPN patients and CCAT2-transgenic mice. The RNA transcribed from the SNP locus in malignant hematopoietic cells have different allelic composition from the corresponding genomic DNA, a phenomenon rarely observed in normal cells. Our findings provide fundamental insights into the functional role of rs6983267 SNP and CCAT2 in myeloid malignancies.
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    IFN-γ and IL-21 Double Producing T Cells Are Bcl6-Independent and Survive into the Memory Phase in Plasmodium chabaudi Infection
    (Public Library of Science (PLoS), 2015) Carpio, Victor H.; Opata, Michael M.; Montañez, Marelle E.; Banerjee, Pinaki P.; Dent, Alexander L.; Stephens, Robin; Department of Microbiology and Immunology, IU School of Medicine
    CD4 T cells are required to fight malaria infection by promoting both phagocytic activity and B cell responses for parasite clearance. In Plasmodium chabaudi infection, one specific CD4 T cell subset generates anti-parasitic IFN-γ and the antibody-promoting cytokine, IL-21. To determine the lineage of these multifunctional T cells, we followed IFN-γ+ effector T cells (Teff) into the memory phase using Ifng-reporter mice. While Ifng+ Teff expanded, the level of the Th1 lineage-determining transcription factor T-bet only peaked briefly. Ifng+ Teff also co-express ICOS, the B cell area homing molecule CXCR5, and other Tfh lineage-associated molecules including Bcl6, the transcription factor required for germinal center (GC) T follicular helper cells (Tfh) differentiation. Because Bcl6 and T-bet co-localize to the nucleus of Ifng+ Teff, we hypothesized that Bcl6 controls the Tfh-like phenotype of Ifng+ Teff cells in P. chabaudi infection. We first transferred Bcl6-deficient T cells into wildtype hosts. Bcl6-deficient T cells did not develop into GC Tfh, but they still generated CXCR5+ IFN-γ+ IL-21+ IL-10+ Teff, suggesting that this predominant population is not of the Tfh-lineage. IL-10 deficient mice, which have increased IFN-γ and T-bet expression, demonstrated expansion of both IFN-γ+ IL-21+ CXCR5+ cells and IFN-γ+ GC Tfh cells, suggesting a Th1 lineage for the former. In the memory phase, all Ifng+ T cells produced IL-21, but only a small percentage of highly proliferative Ifng+ T cells maintained a T-bethi phenotype. In chronic malaria infection, serum IFN-γ correlates with increased protection, and our observation suggests Ifng+ T cells are maintained by cellular division. In summary, we found that Ifng+ T cells are not strictly Tfh derived during malaria infection. T cells provide the host with a survival advantage when facing this well-equipped pathogen, therefore, understanding the lineage of pivotal T cell players will aid in the rational design of an effective malaria vaccine.