A5086518020- Gut microbiota and health
- Single-cell and spatial transcriptomics
- Helicobacter pylori-related gastroenterology studies
- Genomics and Phylogenetic Studies
- Microbial Community Ecology and Physiology
- Diet and metabolism studies
- COVID-19 Clinical Research Studies
- Clostridium difficile and Clostridium perfringens research
- Probiotics and Fermented Foods
- Bacteriophages and microbial interactions
- Inflammatory Bowel Disease
- Gastrointestinal motility and disorders
- Immune Cell Function and Interaction
- Cancer Cells and Metastasis
- T-cell and B-cell Immunology
- SARS-CoV-2 and COVID-19 Research
- Long-Term Effects of COVID-19
- Bacterial Genetics and Biotechnology
- Cancer Genomics and Diagnostics
- Cancer Immunotherapy and Biomarkers
- Congenital gastrointestinal and neural anomalies
- Microscopic Colitis
- Nutritional Studies and Diet
- Tryptophan and brain disorders
- RNA modifications and cancer
Broad Institute
2017-2024
Harvard University
2022-2024
Massachusetts General Hospital
2021-2024
Edinburgh Cancer Research
2023
Massachusetts Institute of Technology
2011-2021
Bankstown Lidcombe Hospital
2014
Sorbonne Université
2010
Institut Pasteur
2010
Centre National de la Recherche Scientifique
2010
University of Arizona
2007-2009
Abstract Single-cell genomics is essential to chart tumor ecosystems. Although single-cell RNA-Seq (scRNA-Seq) profiles RNA from cells dissociated fresh tumors, single-nucleus (snRNA-Seq) needed profile frozen or hard-to-dissociate tumors. Each requires customization different tissue and types, posing a barrier adoption. Here, we have developed systematic toolbox for profiling clinical samples using scRNA-Seq snRNA-Seq, respectively. We analyzed 216,490 nuclei 40 across 23 specimens spanning...
Immune responses to cancer are highly variable, with mismatch repair-deficient (MMRd) tumors exhibiting more anti-tumor immunity than repair-proficient (MMRp) tumors. To understand the rules governing these varied responses, we transcriptionally profiled 371,223 cells from colorectal and adjacent normal tissues of 28 MMRp 34 MMRd individuals. Analysis 88 cell subsets their 204 associated gene expression programs revealed extensive transcriptional spatial remodeling across discover hubs...
Abstract Whether mammal–microbiome interactions are persistent and specific over evolutionary time is controversial. Here we show that host phylogeny major dietary shifts have affected the distribution of different gut bacterial lineages did so on vastly phylogenetic resolutions. Diet mostly influences acquisition ancient large microbial lineages. Conversely, correlation with seen among more recently diverged lineages, consistent processes operating at similar timescales to evolution....
Background Pediatric inflammatory bowel disease (IBD) is challenging to diagnose because of the non-specificity symptoms; an unequivocal diagnosis can only be made using colonoscopy, which clinicians are reluctant recommend for children. Diagnosis pediatric IBD therefore frequently delayed, leading inappropriate treatment plans and poor outcomes. We investigated use 16S rRNA sequencing fecal samples new analytical methods assess differences in microbiota children with other gastrointestinal...
Mechanisms underlying severe coronavirus disease 2019 (COVID-19) remain poorly understood. We analyze several thousand plasma proteins longitudinally in 306 COVID-19 patients and 78 symptomatic controls, uncovering immune non-immune linked to COVID-19. Deconvolution of our proteome data using published scRNA-seq datasets reveals contributions from circulating tissue cells. Sixteen percent display reduced inflammation yet comparably poor outcomes. Comparison who died severely ill survivors...
Biological sensors can be engineered to measure a wide range of environmental conditions. Here we show that statistical analysis DNA from natural microbial communities used accurately identify contaminants, including uranium and nitrate at nuclear waste site. In addition contamination, sequence data the 16S rRNA gene alone quantitatively predict rich catalogue 26 geochemical features collected 93 wells with highly differing geochemistry characteristics. We extend this approach sites...
The intestine is a site of direct encounter with the external environment and must consequently balance barrier defense nutrient uptake. To investigate how uptake regulated in small intestine, we tested effect diets different macronutrient compositions on epithelial gene expression. We found that enzymes transporters required for carbohydrate digestion absorption were by availability. "on-demand" induction this machinery γδ T cells, which program through suppression interleukin-22 production...
Salmonella enterica serovar Typhimurium is a Gram-negative pathogen that causes gastroenteritis in humans and typhoid-like disease mice often used as model for the promoted by human-adapted S. Typhi. Despite its health importance, only strain which complete genomic sequence has been determined avirulent LT2 strain, extensively genetic physiologic studies. Here, we report of 14028s, well those progenitor two additional derivatives. Comparison these genomes revealed differences patterns...
Radiant skin and hair are universally recognized as indications of good health. However, this 'glow health' display remains poorly understood. We found that feeding probiotic bacteria to aged mice induced integumentary changes mimicking peak health reproductive fitness characteristic much younger animals. Eating yogurt triggered epithelial follicular anagen-phase shift with sebocytogenesis resulting in thick lustrous fur due a bacteria-triggered interleukin-10-dependent mechanism. Aged male...
A recent epidemiological study showed that eating 'fast food' items such as potato chips increased likelihood of obesity, whereas yogurt prevented age-associated weight gain in humans. It was demonstrated previously animal models obesity the immune system plays a critical role this process. Here we examined human subjects and mouse consuming Westernized diet, found CD4+ T helper (Th)17-biased immunity changes microbial communities abdominal fat with after Western chow. In striking contrast,...
The gut microbiome is a dynamic system that changes with host development, health, behavior, diet, and microbe-microbe interactions. Prior work on microbial time series has largely focused autoregressive models (e.g. Lotka-Volterra). However, we show most of the variance in non-autoregressive. In addition, how community state-clustering flawed when it comes to characterizing within-host dynamics more continuous methods are required. Most organisms exhibited stable, mean-reverting behavior...
ABSTRACT Genome-wide association studies (GWAS) are a valuable tool for understanding the biology of complex traits, but associations found rarely point directly to causal genes. Here, we introduce new method identify genes by integrating GWAS summary statistics with gene expression, biological pathway, and predicted protein-protein interaction data. We further propose an approach that effectively leverages both polygenic locus-specific genetic signals combining results across multiple...