A5030095493- Gut microbiota and health
- Microscopic Colitis
- Inflammatory Bowel Disease
- Colorectal Cancer Screening and Detection
- Gastrointestinal motility and disorders
- Diet and metabolism studies
- Immune Cell Function and Interaction
- Genetic factors in colorectal cancer
- Gastric Cancer Management and Outcomes
- Clostridium difficile and Clostridium perfringens research
- Cancer survivorship and care
- Genomics and Phylogenetic Studies
- Cancer Genomics and Diagnostics
- Cell Image Analysis Techniques
- Bacteriophages and microbial interactions
- Celiac Disease Research and Management
- Inflammation biomarkers and pathways
- Eosinophilic Esophagitis
- Pancreatic and Hepatic Oncology Research
- Epigenetics and DNA Methylation
- Biomarkers in Disease Mechanisms
- T-cell and B-cell Immunology
- Inflammatory Myopathies and Dermatomyositis
- Dietary Effects on Health
- Cancer Risks and Factors
Fred Hutch Cancer Center
2018-2025
University of Washington
2019-2025
Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa
2022-2025
Washington University in St. Louis
2012-2017
University of California, San Francisco
2008-2013
Yale University
2006-2011
Harvard University
2002
California Institute of Technology
2002
DuPont (United States)
2002
Assam Medical College
1953-1954
Abstract Microbial community profiling using 16S rRNA gene sequences requires accurate taxonomy assignments. ‘Universal’ primers target conserved and amplify from many taxa, but they provide variable coverage of different environments, regions the differ in taxonomic informativeness—especially when high-throughput short-read sequencing technologies (for example, 454 Illumina) are used. We introduce a new evaluation procedure that provides an improved measure expected precision classifying...
The gut microbiome is altered in Crohn's disease. Although individual taxa have been correlated with post-operative clinical course, global trends microbial diversity not described this context. We collected mucosal biopsies from the terminal ileum and ascending colon during surgery colonoscopy 6 patients undergoing ileocolic resection (and 40 additional healthy control either or colonoscopy). Using next-generation sequencing technology, we profiled microbiota order to identify changes...
Background and aims:Vedolizumab inhibits leucocyte vascular adhesion migration into the gastrointestinal tract through α4β7 integrin blockade. This agent became available in mid-2014 for treatment of moderate to severe Crohn's disease (CD) UC (UC). The aim this study was assess patterns use, effectiveness safety vedolizumab an inflammatory bowel (IBD) clinical practice.
Summary: Research on precancers, as defined at-risk tissues and early lesions, is of high significance given the effectiveness intervention. We discuss need for risk stratification to prevent overtreatment, an emphasis role genetic epigenetic aging when considering risk, importance integrating macroenvironmental factors with molecules cells in lesions normal developing effective intervention health policy strategies.
Pathobiont-associated cachexia in a gnotobiotic model of childhood undernutrition is determined by strain-level interactions within the gut microbiota.
Growing evidence indicates a role for the gut microbiota in modulating anti-tumor treatment efficacy human cancer. Here we study mucosa-associated invariant T (MAIT) cells to look of bacterial antigen recognition colon, lung, and kidney carcinomas. Using mass cytometry single-cell mRNA sequencing, identify tumor-infiltrating MAIT cell subset expressing CD4 Foxp3 observe high expression CD39 on from colorectal cancer (CRC) only, which show vitro be expressed specifically after TCR...
COVID-19 (coronavirus disease 2019) patients exhibiting gastrointestinal symptoms are reported to have worse prognosis. Ace2 (angiotensin-converting enzyme 2), the gene encoding host protein which SARS-CoV-2 spike proteins bind, is expressed in gut and therefore may be a target for preventing or reducing severity of COVID-19. Here we test hypothesis that expression respiratory tracts modulated by microbiome. We used quantitative PCR profile germ-free mice, conventional raised specific...
Gut motility is regulated by the microbiome via mechanisms that include bile acid metabolism. To localize effects of microbiome-generated acids, we colonized gnotobiotic mice with different synthetic gut bacterial communities were metabolically phenotyped using a functional in vitro screen. Using two marker-based assays transit, inferred acids exert on colonic transit. We validated this an intra-colonic infusion assay and determined these dependent upon signaling receptor, TGR5. The...
Success of phage therapies is limited by bacterial defenses against phages. While a large variety anti- defense mechanisms has been characterized, how expression these systems distributed across individual cells and their combined activities translate into protection from phages not studied. Using single-cell RNA sequencing, we profiled the transcriptomes ∼50,000 cultures human pathobiont, Bacteroides fragilis, infected with lytic bacteriophage. We quantified asynchronous progression...
Colorectal cancer (CRC) is a globally prevalent cancer. Emerging research implicates the gut microbiome in CRC pathogenesis. Bacteria such as Clostridium scindens can produce carcinogenic bile acid deoxycholic (DCA). It unknown whether imaging methods differentiate DCA-producing and DCA-non-producing C. cells. Light microscopy images of anaerobically cultured four conditions were acquired at 100× magnification using Tissue FAX system: media alone (DCA-non-producing state), with cholic...
ABSTRACT Human cytomegalovirus (HCMV) US10 encodes a glycoprotein that binds to major histocompatibility complex (MHC) class I heavy chains. While expression of delays the normal trafficking MHC molecules out endoplasmic reticulum, does not obviously facilitate or inhibit action two other HCMV-encoded binding proteins, US2 and US11.
The oral and colonic microbiota are distinct in healthy individuals. However, this distinction is diminished common diseases such as colon cancer inflammatory bowel disease, suggesting a potential pathogenic role for bacteria when ectopically colonized the gut. A key mechanism segregation of niches thought to be microbiota-mediated colonization resistance whereby commensal gut outcompete eliminate ingested bacteria.We tested theory by analyzing exact amplicon sequence variants generated from...
Abstract The multitude of barriers between the mouth and colon may eliminate swallowed oral bacteria. Ascertaining presence same bacteria in is methodologically challenging partly because 16S rRNA gene sequencing – most commonly used method to characterize human microbiota has low confidence taxonomic assignments deeper than genus for As different species can have low-level variation across region, shotgun needed identify a true overlap. We analyzed curated, multi-cohort, metagenomic...
Summary We showed that hepatic Vα14 + invariant natural killer T (iNKT) cells, via their rapid interleukin (IL)‐4 production, activate B‐1 cells to initiate contact sensitivity (CS). This innate collaboration was absent in IL‐4 –/– and signal transducer activator of transcription (STAT)‐6 mice inhibited by anti‐IL‐4 treatment. These have defective CS because they fail locally recruit the sensitized effector acquired immunity. Their is reconstituted transfer downstream‐acting 1‐day immune...
Natural killer T cells with invariant αβ-T cell receptors (TCRs) (iNKT cells) constitute a lipid-responsive arm of the innate immune system that has been implicated in regulation or promotion various immune, infectious and neoplastic processes. Contact sensitivity (CS), also known as contact hypersensitivity allergic dermatitis, is one such process begins topical sensitization to an allergen culminates localized cutaneous inflammatory response after challenge same allergen. CS depends on...
Gastrointestinal motility is regulated by a variety of environmental factors including gut microbes and metabolites. The ability to interrogate mouse models has enabled elucidation these relationships. Here we describe integration the red carmine dye fluorescence isothiocyanate-dextran marker-based assays for characterizing transit with spatial resolution, along an optional intracolonic infusion protocol studying effects metabolites on colonic transit. These protocols can be adapted use in...
The gut microbiome is implicated in the pathogenesis of colorectal cancer (CRC), but full scope this dialogue unknown. Here we aimed to define scale and membership body CRC- health-associated bacteria global populations. We performed a microbiome-CRC correlation analysis published ultra-deep shotgun metagenomic sequencing data from surveys, utilizing de novo (reference-agnostic) gene-level clustering approach identify protein-coding co-abundant gene (CAGs) clusters. link an unprecedented ~...