A5082949276- Gut microbiota and health
- Genomics and Phylogenetic Studies
- Gene expression and cancer classification
- Metabolomics and Mass Spectrometry Studies
- Bacteriophages and microbial interactions
- Clostridium difficile and Clostridium perfringens research
- Microbial Community Ecology and Physiology
- Plant Virus Research Studies
- Epigenetics and DNA Methylation
- Mycobacterium research and diagnosis
- Viral gastroenteritis research and epidemiology
- Oral microbiology and periodontitis research
- Respiratory viral infections research
- Oral health in cancer treatment
- Reproductive tract infections research
- Head and Neck Cancer Studies
- Pancreatic and Hepatic Oncology Research
- Colorectal Cancer Screening and Detection
- Bacterial Identification and Susceptibility Testing
- Herpesvirus Infections and Treatments
- Monoclonal and Polyclonal Antibodies Research
- RNA modifications and cancer
- Probiotics and Fermented Foods
- Pelvic floor disorders treatments
- HIV Research and Treatment
Fred Hutch Cancer Center
2018-2025
Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa
2022-2025
Infectious Disease Research Institute
2020-2024
North Seattle College
2024
Seattle University
2024
Cancer Research Center
2020-2022
Codexis (United States)
2016-2017
University of Pennsylvania
2011-2015
Bowdoin College
2014-2015
Signature Research (United States)
2014
Immense populations of viruses are present in the human gut and other body sites. Understanding role these (the “virome”) health disease requires a much deeper understanding their composition dynamics face environmental perturbation. Here, we investigate viromes from subjects on controlled feeding regimen. Longitudinal fecal samples were analyzed by metagenomic sequencing DNA virus-like particles (VLP) total microbial communities. Assembly 336 Mb VLP sequence yielded 7175 contigs, many...
Humans are colonized by immense populations of viruses, which metagenomic analysis shows mostly unique to each individual. To investigate the origin and evolution human gut virome, we analyzed viral community one adult individual over 2.5 y extremely deep sequencing (56 billion bases purified sequence from 24 longitudinal fecal samples). After assembly, 478 well-determined contigs could be identified, inferred correspond previously unstudied bacteriophage genomes. Fully 80% these types...
Abstract The tumour-associated microbiota is an intrinsic component of the tumour microenvironment across human cancer types 1,2 . Intratumoral host–microbiota studies have so far largely relied on bulk tissue analysis 1–3 , which obscures spatial distribution and localized effect within tumours. Here, by applying in situ spatial-profiling technologies 4 single-cell RNA sequencing 5 to oral squamous cell carcinoma colorectal cancer, we reveal spatial, cellular molecular host–microbe...
One of the main challenges in metagenomics is identification microorganisms clinical and environmental samples. While an extensive heterogeneous set computational tools available to classify using whole-genome shotgun sequencing data, comprehensive comparisons these methods are limited. In this study, we use largest-to-date laboratory-generated simulated controls across 846 species evaluate performance 11 metagenomic classifiers. Tools were characterized on basis their ability identify taxa...
Viruses make up a major component of the human microbiota but are poorly understood in skin, our primary barrier to external environment. Viral communities have potential modulate states cutaneous health and disease. Bacteriophages known influence structure function microbial through predation genetic exchange. Human viruses associated with skin cancers multitude manifestations. Despite these important roles, little is regarding virome its interactions host microbiome. Here we evaluated...
Abstract Fusobacterium nucleatum ( Fn ), a bacterium present in the human oral cavity and rarely found lower gastrointestinal tract of healthy individuals 1 , is enriched colorectal cancer (CRC) tumours 2–5 . High intratumoural loads are associated with recurrence, metastases poorer patient prognosis 5–8 Here, to delineate genetic factors facilitating tumour colonization, we generated closed genomes for 135 strains; 80 strains from without 55 unique cultured 51 patients CRC. Pangenomic...
Fusobacterium nucleatum (Fn) is a dominant bacterial species in colorectal cancer (CRC) tissue that associated with progression and poorer patient prognosis. Following small-molecule inhibitor screen of 1,846 bioactive compounds against Fn CRC isolate, we find 15% inhibitors are antineoplastic agents including fluoropyrimidines. Validation these findings reveals 5-fluorouracil (5-FU), first-line chemotherapeutic, potent isolates. We also identify members the intratumoral microbiota,...
Genetic variation is critical in microbial immune evasion and drug resistance, but has rarely been studied complex heterogeneous communities such as the human microbiome. To begin to study natural variation, we analyzed DNA viruses present lower gastrointestinal tract of 12 volunteers by determining 48 billion bases viral sequence. Viral genomes mostly showed low 51 loci ∼100 bp extremely high so that up 96% encoded unique amino acid sequences. Some hotspots hypervariation were genes...
Abstract Background The MinION™ nanopore sequencer was recently released to a community of alpha-testers for evaluation using variety sequencing applications. Recent reports have tested the ability act as whole genome and demonstrated that has tremendous potential utility. However, current technology still limitations with respect error-rate, this is problematic when attempting assemble genomes without secondary rounds correct errors. In study, we accurately identify differentiate bacterial...
1 ABSTRACT High-throughput sequencing (HTS) is increasingly being used for broad applications of microbial char-acterization, such as ecology, clinical diagnosis, and outbreak epidemiology. However, the analytical task comparing short sequence reads against known diversity life has proved to be computationally challenging. The One Codex data platform was created with dual goals analyzing largest possible collection reference genomes, well presenting those results in a format that consumable...
Environmental metagenomic analysis is typically accomplished by assigning taxonomy and/or function from whole genome sequencing or 16S amplicon sequences. Both of these approaches are limited, however, read length, among other technical and biological factors. A nanopore-based platform, MinION™, produces reads that ≥1 × 104 bp in potentially providing for more precise assignment, thereby alleviating some the limitations inherent determining metagenome composition short reads. We tested...
More than 2 months separated the initial description of SARS-CoV-2 and discovery its widespread dissemination in United States. Despite this lengthy interval, implementation specific quantitative reverse transcription (qRT)-PCR-based tests US has been slow, testing is still not widely available. Metagenomic sequencing offers promise unbiased detection emerging pathogens, without requiring prior knowledge identity responsible agent or genomic sequence.To evaluate metagenomic approaches...
Toxoplasma gondii is a highly successful protozoan parasite that infects all warm-blooded animals and causes severe disease in immunocompromised immune-naïve humans. It has an unusual global population structure: In North America Europe, isolated strains fall predominantly into four largely clonal lineages, but South there great genetic diversity the American lineages are rarely found. Genetic variation between determines differences virulence, modulation of host-signaling pathways, growth,...
The infectious form of many parasitic nematodes, which afflict over one billion people globally, is a developmentally arrested third-stage larva (L3i). nematode Strongyloides stercoralis differs from other species that infect humans, in its life cycle includes both and free-living forms, can be leveraged to investigate the mechanisms L3i arrest activation. Caenorhabditis elegans has similar larval form, dauer, whose formation controlled by four pathways: cyclic GMP (cGMP) signaling,...
Understanding the axis of human microbiome and physiological homeostasis is an essential task in managing deep-space-travel-associated health risks. The NASA-led Rodent Research 5 mission enabled ancillary investigation gut microbiome, varying exposure to microgravity (flight) relative ground controls context previously shown bone mineral density (BMD) loss that was observed these flight groups. We demonstrate elevated abundance Lactobacillus murinus Dorea sp. during control through...
Every year, 11% of infants are born preterm with significant health consequences, the vaginal microbiome a risk factor for birth. We crowdsource models to predict (1) birth (PTB; <37 weeks) or (2) early (ePTB; <32 from 9 studies representing 3,578 samples 1,268 pregnant individuals, aggregated public raw data via phylogenetic harmonization. The predictive validated on two independent unpublished datasets 331 148 individuals. top-performing (among and 121 submissions 318 teams) achieve area...
Significance Mites live in human hair follicles and have been implicated medically important skin disorders, but we know surprisingly little about these residents of our skin. By analyzing the variation segregating among 241 mite sequences isolated from 70 hosts, showed that hosts with different regional ancestries harbor distinct lineages mites associations can persist despite generations spent a new geographic region. These results suggest some populations are better able to survive...
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...
Abstract Mathematical modeling of somatic evolution, a process impacting both host cells and microbial communities in the human body, can capture important dynamics driving carcinogenesis. Here we considered models for esophageal adenocarcinoma (EAC), cancer that has dramatically increased incidence over past few decades Western populations, with high case fatality rates due to late-stage diagnoses. Despite advancements genomic analyses precursor Barrett’s esophagus (BE), prevention EAC...
Gut microbiota disruptions after allogeneic hematopoietic cell transplantation (alloHCT) are associated with increased risk of acute graft-versus-host disease (aGVHD). We designed a randomized, double-blind placebo-controlled trial to test whether healthy-donor fecal (FMT) early alloHCT reduces the incidence severe aGVHD. Here, we report results from single-arm run-in phase which identified best 3 stool donors for randomized phase. The primary and key secondary endpoints were engraftment...
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...