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Gandhi, Roopali

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Gandhi

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Roopali

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Gandhi, Roopali
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Now showing 1 - 7 of 7
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    Alterations of the human gut microbiome in multiple sclerosis
    (Nature Publishing Group, 2016) Jangi, Sushrut; Gandhi, Roopali; Cox, Laura; Li, Ning; von Glehn, Felipe; Yan, Raymond; Patel, Bonny; Mazzola, Maria; Liu, Shirong; Glanz, Bonnie; Cook, Sandra; Tankou, Stephanie; Stuart, Fiona; Melo, Kirsy; Nejad, Parham; Smith, Kathleen; Topçuolu, Begüm D.; Holden, James; Kivisakk, Pia; Chitnis, Tanuja; De Jager, Philip; Quintana, Francisco; Gerber, Georg; Bry, Lynn; Weiner, Howard
    The gut microbiome plays an important role in immune function and has been implicated in several autoimmune disorders. Here we use 16S rRNA sequencing to investigate the gut microbiome in subjects with multiple sclerosis (MS, n=60) and healthy controls (n=43). Microbiome alterations in MS include increases in Methanobrevibacter and Akkermansia and decreases in Butyricimonas, and correlate with variations in the expression of genes involved in dendritic cell maturation, interferon signalling and NF-kB signalling pathways in circulating T cells and monocytes. Patients on disease-modifying treatment show increased abundances of Prevotella and Sutterella, and decreased Sarcina, compared with untreated patients. MS patients of a second cohort show elevated breath methane compared with controls, consistent with our observation of increased gut Methanobrevibacter in MS in the first cohort. Further study is required to assess whether the observed alterations in the gut microbiome play a role in, or are a consequence of, MS pathogenesis.
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    Effect of Natalizumab Treatment on Circulating Plasmacytoid Dendritic Cells: A Cross-Sectional Observational Study in Patients with Multiple Sclerosis
    (Public Library of Science, 2014) Kivisakk, Pia; Francois, Katiana; Mbianda, Julvet; Gandhi, Roopali; Weiner, Howard; Khoury, Samia
    Objectives: Dendritic cells (DCs) serve a critical role both in promoting and inhibiting adaptive immunity. The goal of this study was to investigate the effect of natalizumab (NTZ) treatment on DC numbers, phenotype, and function in patients with multiple sclerosis (MS). Methods: Frequency and phenotype of myeloid and plasmacytoid DCs (MDCs and PDCs, respectively) were analyzed in blood from two separate cohorts of untreated, interferon-treated, or NTZ-treated MS patients. In addition, PDCs were stimulated with CpG-containing oligonucleotides or co-cultured with homologous T cells in the presence or absence of NTZ in vitro to determine functional effects of NTZ treatment. Results: We observed that NTZ treatment was associated with a 25–50% reduction in PDC frequency in peripheral blood as compared to untreated MS patients, while the frequency of MDCs was unchanged. PDCs in NTZ-treated patients displayed a mature, activated phenotype with increased expression of HLA-DR, TLR9, CCR7, IL-6 and IL-12. In contrast, in vitro treatment with NTZ did not increase markers of PDC activation or their ability to induce T cell differentiation. Conclusion: Our study shows that NTZ treatment is associated with a reduced frequency of PDCs in the peripheral circulation, but that PDCs in NTZ-treated individuals display an activated phenotype. Taken together the data suggests that transmigration of activated PDCs is preferentially affected by blockade of integrin α4 leading to an increased frequency of activated PDCs in blood.
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    Identification of a novel mechanism of action of fingolimod (FTY720) on human effector T cell function through TCF-1 upregulation
    (BioMed Central, 2015) Mazzola, Maria; Raheja, Radhika; Murugaiyan, Gopal; Rajabi, Hasan; Kumar, Deepak; Pertel, Thomas; Regev, Keren; Griffin, Russell; Aly, Lilian; Kivisakk, Pia; Nejad, Parham; Patel, Bonny; Gwanyalla, Nguendab; Hei, Hillary; Glanz, Bonnie; Chitnis, Tanuja; Weiner, Howard; Gandhi, Roopali
    Background: Fingolimod (FTY720), the first oral treatment for multiple sclerosis (MS), blocks immune cell trafficking and prevents disease relapses by downregulation of sphingosine-1-phosphate receptor. We determined the effect of FTY720 on human T cell activation and effector function. Methods: T cells from MS patients and healthy controls were isolated to measure gene expression profiles in the presence or absence of FTY720 using nanostring and quantitative real-time polymerase chain reaction (qPCR). Cytokine protein expression was measured using luminex assay and flow cytometry analysis. Lentivirus vector carrying short hairpin RNA (shRNA) was used to knock down the expression of specific genes in CD4+ T cells. Chromatin immunoprecipitation was performed to assess T cell factor 1 (TCF-1) binding to promoter regions. Luciferase assays were performed to test the direct regulation of interferon gamma (IFN-γ) and granzyme B (GZMB) by TCF-1. Western blot analysis was used to assess the phosphorylation status of Akt and GSK3β. Results: We showed that FTY720 treatment not only affects T cell trafficking but also T cell activation. Patients treated with FTY720 showed a significant reduction in circulating CD4 T cells. Activation of T cells in presence of FTY720 showed a less inflammatory phenotype with reduced production of IFN-γ and GZMB. This decreased effector phenotype of FTY720-treated T cells was dependent on the upregulation of TCF-1. FTY720-induced TCF-1 downregulated the pathogenic cytokines IFN-γ and GZMB by binding to their promoter/enhancer regions and mediating epigenetic modifications. Furthermore, we observed that TCF-1 expression was lower in T cells from multiple sclerosis patients than in those from healthy individuals, and FTY720 treatment increased TCF-1 expression in multiple sclerosis patients. Conclusions: These results reveal a previously unknown mechanism of the effect of FTY720 on human CD4+ T cell modulation in multiple sclerosis and demonstrate the role of TCF-1 in human T cell activation and effector function. Electronic supplementary material The online version of this article (doi:10.1186/s12974-015-0460-z) contains supplementary material, which is available to authorized users.
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    Quantitative MRI study of Pineal Gland in MS.
    (2016) Egorova, Svetlana; Denes, Palma; Polgar-Turcsanyi, Mariann; Anderson, Mark; Cavallari, Michele; Guttmann, Charles; Glanz, Bonnie; Chitnis, Tanuja; Bove, Riley; Buckle, Guy; De Jager, Philip; Severson, Cristopher; Stankiewicz, James; Houtchens, Maria; Quintana, Francisco; Gandhi, Roopali; Webb, Pia; Meier, Dominik; Healy, Brian; Weiner, Howard
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    Comprehensive evaluation of serum microRNAs as biomarkers in multiple sclerosis
    (Lippincott Williams & Wilkins, 2016) Regev, Keren; Paul, Anu; Healy, Brian; von Glenn, Felipe; Diaz-Cruz, Camilo; Gholipour, Taha; Mazzola, Maria; Raheja, Radhika; Nejad, Parham; Glanz, Bonnie; Kivisakk, Pia; Chitnis, Tanuja; Weiner, Howard; Gandhi, Roopali
    Objective: To identify circulating microRNAs (miRNAs) linked to disease stage and disability in multiple sclerosis (MS). Methods: Sera from 296 participants including patients with MS, other neurologic diseases (Alzheimer disease and amyotrophic lateral sclerosis), and inflammatory diseases (rheumatoid arthritis and asthma) and healthy controls (HCs) were tested. miRNA profiles were determined using LNA (locked nucleic acid)-based quantitative PCR. Patients with MS were categorized according to disease stage and disability. In the discovery phase, 652 miRNAs were measured in sera from 26 patients with MS and 20 HCs. Following this, significant miRNAs (p < 0.05) from the discovery set were validated using quantitative PCR in 58 patients with MS, 30 HCs, and in 74 samples from other disease controls (Alzheimer disease, amyotrophic lateral sclerosis, asthma, and rheumatoid arthritis). Results: We validated 7 miRNAs that differentiate patients with MS from HCs (p < 0.05 in both the discovery and validation phase); miR-320a upregulation was the most significantly changing serum miRNA in patients with MS. We also identified 2 miRNAs linked to disease progression, with miR-27a-3p being the most significant. Ten miRNAs correlated with the Expanded Disability Status Scale of which miR.199a.5p had the strongest correlation with disability. Of the 15 unique miRNAs we identified in the different group comparisons, 12 have previously been reported to be associated with MS but not in serum. Conclusions: Our findings identify circulating serum miRNAs as potential biomarkers to diagnose and monitor disease status in MS. Classification of evidence: This study provides Class III evidence that circulating serum miRNAs can be used as biomarker for MS.
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    Extracellular RNAs: development as biomarkers of human disease
    (Co-Action Publishing, 2015) Quinn, Joseph F.; Patel, Tushar; Wong, David; Das, Saumya; Freedman, Jane E.; Laurent, Louise C.; Carter, Bob S.; Hochberg, Fred; Keuren-Jensen, Kendall Van; Huentelman, Matt; Spetzler, Robert; Kalani, M. Yashar S.; Arango, Jorge; Adelson, P. David; Weiner, Howard; Gandhi, Roopali; Goilav, Beatrice; Putterman, Chaim; Saugstad, Julie A.
    Ten ongoing studies designed to test the possibility that extracellular RNAs may serve as biomarkers in human disease are described. These studies, funded by the NIH Common Fund Extracellular RNA Communication Program, examine diverse extracellular body fluids, including plasma, serum, urine and cerebrospinal fluid. The disorders studied include hepatic and gastric cancer, cardiovascular disease, chronic kidney disease, neurodegenerative disease, brain tumours, intracranial haemorrhage, multiple sclerosis and placental disorders. Progress to date and the plans for future studies are outlined.
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    Meeting report: discussions and preliminary findings on extracellular RNA measurement methods from laboratories in the NIH Extracellular RNA Communication Consortium
    (Co-Action Publishing, 2015) Laurent, Louise C.; Abdel-Mageed, Asim B.; Adelson, P. David; Arango, Jorge; Balaj, Leonora; Breakefield, Xandra; Carlson, Elizabeth; Carter, Bob S.; Majem, Blanca; Chen, Clark C.; Cocucci, Emanuele; Danielson, Kirsty; Courtright, Amanda; Das, Saumya; Elmageed, Zakaria Y. Abd; Enderle, Daniel; Ezrin, Alan; Ferrer, Marc; Freedman, Jane; Galas, David; Gandhi, Roopali; Huentelman, Matthew J.; Van Keuren-Jensen, Kendall; Kalani, Yashar; Kim, Yong; Krichevsky, Anna; Lai, Charles; Lal-Nag, Madhu; Laurent, Clara D.; Leonardo, Trevor; Li, Feng; Malenica, Ivana; Mondal, Debasis; Nejad, Parham; Patel, Tushar; Raffai, Robert L.; Rubio, Renee; Skog, Johan; Spetzler, Robert; Sun, Jie; Tanriverdi, Kahraman; Vickers, Kasey; Wang, Liang; Wang, Yaoyu; Wei, Zhiyun; Weiner, Howard; Wong, David; Yan, Irene K.; Yeri, Ashish; Gould, Stephen
    Extracellular RNAs (exRNAs) have been identified in all tested biofluids and have been associated with a variety of extracellular vesicles, ribonucleoprotein complexes and lipoprotein complexes. Much of the interest in exRNAs lies in the fact that they may serve as signalling molecules between cells, their potential to serve as biomarkers for prediction and diagnosis of disease and the possibility that exRNAs or the extracellular particles that carry them might be used for therapeutic purposes. Among the most significant bottlenecks to progress in this field is the lack of robust and standardized methods for collection and processing of biofluids, separation of different types of exRNA-containing particles and isolation and analysis of exRNAs. The Sample and Assay Standards Working Group of the Extracellular RNA Communication Consortium is a group of laboratories funded by the U.S. National Institutes of Health to develop such methods. In our first joint endeavour, we held a series of conference calls and in-person meetings to survey the methods used among our members, placed them in the context of the current literature and used our findings to identify areas in which the identification of robust methodologies would promote rapid advancements in the exRNA field.