Browsing by Author "Xavier, Ramnik J."
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Adaptive Evolution within Gut Microbiomes of Healthy People
Zhao, Shijie; Lieberman, Tami; Poyet, Mathilde; Kauffman, Kathryn; Gibbons, Sean M.; e.a. (Elsevier BV, 2019-05)Natural selection shapes bacterial evolution in all environments. However, the extent to which commensal bacteria diversify and adapt within the human gut remains unclear. Here, we combine culture-based population genomics ... -
Atg16L1 T300A variant decreases selective autophagy resulting in altered cytokine signaling and decreased antibacterial defense
Lassen, Kara G.; Kuballa, Petric; Conway, Kara L.; Patel, Khushbu; Becker, Christine E.; e.a. (National Academy of Sciences (U.S.), 2014-05)A coding polymorphism (Thr300Ala) in the essential autophagy gene, autophagy related 16-like 1 (ATG16L1), confers increased risk for the development of Crohn disease, although the mechanisms by which single disease-associated ... -
Calcitonin Gene-Related Peptide Negatively Regulates Alarmin-Driven Type 2 Innate Lymphoid Cell Responses
Wallrapp, Antonia; Burkett, Patrick R.; Riesenfeld, Samantha J.; Kim, Se-Jin; Christian, Elena; e.a. (Elsevier BV, 2019-10)Neuroimmune interactions have emerged as critical modulators of allergic inflammation, and type 2 innate lymphoid cells (ILC2s) are an important cell type for mediating these interactions. Here, we show that ILC2s expressed ... -
Comprehensive analysis of chromosomal mobile genetic elements in the gut microbiome reveals phylum-level niche-adaptive gene pools
Jiang, Xiaofang; Hall, Andrew Brantley; Xavier, Ramnik J.; Alm, Eric J. (Public Library of Science (PLoS), 2019-12-12)Mobile genetic elements (MGEs) drive extensive horizontal transfer in the gut microbiome. This transfer could benefit human health by conferring new metabolic capabilities to commensal microbes, or it could threaten human ... -
Congruent microbiome signatures in fibrosis-prone autoimmune diseases: IgG4-related disease and systemic sclerosis
Plichta, Damian R.; Somani, Juhi; Pichaud, Matthieu; Wallace, Zachary S.; Fernandes, Ana D.; e.a. (BioMed Central, 2021-02-28)Abstract Background Immunoglobulin G4-related disease (IgG4-RD) and systemic sclerosis (SSc) are rare autoimmune diseases characterized by the presence of CD4+ cytotoxic T ... -
Control and Manipulation of Pathogens with an Optical Trap for Live Cell Imaging of Intercellular Interactions
Tam, Jenny M.; Castro, Carlos E.; Heath, Robert J. W.; Cardenas, Michael L.; Xavier, Ramnik J.; e.a. (Public Library of Science, 2010-12)The application of live cell imaging allows direct visualization of the dynamic interactions between cells of the immune system. Some preliminary observations challenge long-held beliefs about immune responses to microorganisms; ... -
Gut bacterial metabolites modulate endoplasmic reticulum stress
Ke, Xiaobo; You, Kwontae; Pichaud, Matthieu; Haiser, Henry J.; Graham, Daniel B.; e.a. (BioMed Central, 2021-10)Background The endoplasmic reticulum (ER) is a membranous organelle that maintains proteostasis and cellular homeostasis, controlling the fine balance between health and disease. Dysregulation of the ER ... -
Identifying Relationships among Genomic Disease Regions: Predicting Genes at Pathogenic SNP Associations and Rare Deletions
Daly, Mark J.; Altshuler, David; Xavier, Ramnik J.; Sklar, Pamela; Purcell, Shaun M.; e.a. (Public Library of Science, 2009-06)Translating a set of disease regions into insight about pathogenic mechanisms requires not only the ability to identify the key disease genes within them, but also the biological relationships among those key genes. Here ... -
Identifying relationships among genomic disease regions: predicting= pathogenic SNP associations and rare deletions
Raychaudhuri, Soumya; Plenge, Robert M.; Rossin, Elizabeth; Ng, Aylwin C. Y.; Purcell, Shaun M.; e.a. (Public Library of Science, 2009-06)Translating a set of disease regions into insight about pathogenic mechanisms requires not only the ability to identify the key disease genes within them, but also the biological relationships among those key genes. Here ... -
The influence of the gut microbiome on BCG-induced trained immunity
Stražar, Martin; Mourits, Vera P.; Koeken, Valerie A. C. M.; de Bree, L. C. J.; Moorlag, Simone J. C. F. M.; e.a. (BioMed Central, 2021-09)Abstract Background The bacillus Calmette-Guérin (BCG) vaccine protects against tuberculosis and heterologous infections but elicits high inter-individual variation in ... -
Invertible promoters mediate bacterial phase variation, antibiotic resistance, and host adaptation in the gut
Jiang, Xiaofang; Hall, A. Brantley; Arthur, Timothy D.; Plitchta, Damian R.; Covington, Christian T.; e.a. (American Association for the Advancement of Science (AAAS), 2019-01)Phase variation, the reversible alternation between genetic states, enables infection by pathogens and colonization by commensals. However, the diversity of phase variation remains underexplored. We developed the PhaseFinder ... -
Mutations causing medullary cystic kidney disease type 1 lie in a large VNTR in MUC1 missed by massively parallel sequencing
Kirby, Andrew; Gnirke, Andreas; Jaffe, David B.; Baresova, Veronika; Pochet, Nathalie; e.a. (Nature Publishing Group, 2013-02)Although genetic lesions responsible for some mendelian disorders can be rapidly discovered through massively parallel sequencing of whole genomes or exomes, not all diseases readily yield to such efforts. We describe the ... -
Non-Invasive Mapping of the Gastrointestinal Microbiota Identifies Children with Inflammatory Bowel Disease
Papa, Eli; Docktor, Michael; Smillie, Christopher; Weber, Sarah; Preheim, Sarah Pacocha; e.a. (Public Library of Science, 2012-06)Background: Pediatric inflammatory bowel disease (IBD) is challenging to diagnose because of the non-specificity of symptoms; an unequivocal diagnosis can only be made using colonoscopy, which clinicians are reluctant ... -
A novel Ruminococcus gnavus clade enriched in inflammatory bowel disease patients
Hall, Andrew Brantley; Yassour, Moran; Sauk, Jenny; Garner, Ashley; Jiang, Xiaofang; e.a. (Biomed Central Ltd, 2017-11)Background: Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract that is associated with changes in the gut microbiome. Here, we sought to identify strain-specific functional ... -
Proteins encoded in genomic regions associated with immune-mediated disease physically interact and suggest underlying biology
Rossin, Elizabeth; Lage, Kasper; Raychaudhuri, Soumya; Xavier, Ramnik J.; Tatar, Diana; e.a. (Public Library of Science, 2011-01)Genome-wide association studies have uncovered hundreds of DNA changes associated with complex disease. The ultimate promise of these studies is the understanding of disease biology; this goal, however, is not easily ... -
A single-cell survey of the small intestinal epithelium
Haber, Adam L.; Biton, Moshe; Rogel, Noga; Herbst, Rebecca H.; Shekhar, Karthik; e.a. (Nature Publishing Group, 2017-11)Intestinal epithelial cells absorb nutrients, respond to microbes, function as a barrier and help to coordinate immune responses. Here we report profiling of 53,193 individual epithelial cells from the small intestine and ... -
Small-molecule enhancers of autophagy modulate cellular disease phenotypes suggested by human genetics
Kuo, Szu-Yu; Castoreno, Adam B.; Aldrich, Leslie N.; Lassen, Kara G.; Goel, Gautam; e.a. (National Academy of Sciences (U.S.), 2015-08)Studies of human genetics and pathophysiology have implicated the regulation of autophagy in inflammation, neurodegeneration, infection, and autoimmunity. These findings have motivated the use of small-molecule probes to ... -
Strain-Level Analysis of Mother-to-Child Bacterial Transmission during the First Few Months of Life
Yassour, Moran; Jason, Eeva; Hogstrom, Larson J.; Arthur, Timothy D.; Tripathi, Surya; e.a. (Elsevier BV, 2018-07)Bacterial community acquisition in the infant gut impacts immune education and disease susceptibility. We compared bacterial strains across and within families in a prospective birth cohort of 44 infants and their mothers, ... -
Sub-clinical detection of gut microbial biomarkers of obesity and type 2 diabetes
Yassour, Moran; Lim, Mi Young; Yun, Hyun Sun; Tickle, Timothy L.; Sung, Joohon; e.a. (Biomed Central Ltd, 2016-02)Background: Obesity and type 2 diabetes (T2D) are linked both with host genetics and with environmental factors, including dysbioses of the gut microbiota. However, it is unclear whether these microbial changes precede ... -
Transcriptional Atlas of Intestinal Immune Cells Reveals that Neuropeptide α-CGRP Modulates Group 2 Innate Lymphoid Cell Responses
Xu, Heping; Ding, Jiarui; Porter, Caroline; Wallrapp, Antonia; Tabaka, Marcin; e.a. (Elsevier BV, 2019-10)Signaling abnormalities in immune responses in the small intestine can trigger chronic type 2 inflammation involving interaction of multiple immune cell types. To systematically characterize this response, we analyzed ...