A5057141495- Bacteriophages and microbial interactions
- Genomics and Phylogenetic Studies
- T-cell and B-cell Immunology
- Evolution and Genetic Dynamics
- Immune Cell Function and Interaction
- Cancer Immunotherapy and Biomarkers
- Evolutionary Game Theory and Cooperation
- Plant Virus Research Studies
- Insect symbiosis and bacterial influences
- Urinary Tract Infections Management
- Gut microbiota and health
- Genetics, Bioinformatics, and Biomedical Research
- Microbial infections and disease research
- Microbial Community Ecology and Physiology
- Dermatology and Skin Diseases
- Probiotics and Fermented Foods
- CAR-T cell therapy research
- Intraperitoneal and Appendiceal Malignancies
- Appendicitis Diagnosis and Management
- Angiogenesis and VEGF in Cancer
- Single-cell and spatial transcriptomics
- Urinary Bladder and Prostate Research
- Mathematical and Theoretical Epidemiology and Ecology Models
- Cell Adhesion Molecules Research
- Mycobacterium research and diagnosis
University of Chicago
2017-2024
Loyola University Chicago
2016-2021
Yale University
2013-2018
University of Minnesota
2014-2016
Biotechnology Institute
2016
Abstract Immune checkpoint blockade is therapeutically successful for many patients across multiple cancer types. However, immune-related adverse events (irAE) frequently occur and can sometimes be life threatening. It critical to understand the immunologic mechanisms of irAEs with goal finding novel treatment targets. Herein, we report our analysis tissues from irAE dermatitis using multiparameter immunofluorescence (IF), spatial transcriptomics, RNA in situ hybridization (RISH). Skin...
The cellular source of positive signals that reinvigorate T cells within the tumor microenvironment (TME) for therapeutic efficacy programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) blockade has not been clearly defined. We now show Batf3-lineage dendritic (DCs) are essential in this process. Flow cytometric analysis, gene-targeted mice, and blocking antibody studies revealed 4-1BBL is a major co-stimulatory signal provided by these DCs TME translates to CD8
While past work has often examined the effects of transmission mode on virulence evolution in parasites, few studies have explored impact horizontal benefits conferred by a symbiont to its host. Here, we identify three mechanisms that create positive covariance between and symbiont-provided benefits: pleiotropy within genome, partner choice host, consumption host waste by-products symbionts. We modify susceptible-infected model incorporate details each mechanism examine given variation...
While theory suggests conditions under which mutualism may evolve from parasitism, few studies have observed this transition empirically. Previously, we evolved Escherichia coli and the filamentous bacteriophage M13 in 96-well microplates, an environment ancestral phage increased growth rate yield of bacteria. In majority populations, was maintained or even enhanced between phages coevolving bacteria; however, these same traits that harmed E. genotype. Here, set out to determine if could new...
Urinary tract infections (UTIs) are one of the most common human bacterial infections. While UTIs commonly associated with colonization by Escherichia coli, members this species also have been found within bladder individuals no lower urinary symptoms (no LUTS), known as asymptomatic bacteriuria. Prior studies that both uropathogenic E. coli (UPEC) strains and isolates not encode for virulence factors. Thus, reason(s) why sometimes causes UTI-like remain(s) elusive. In study, genomes 66 from...
ABSTRACT Bacteriophages are the most abundant and diverse biological entities on planet, new phage genomes being discovered at a rapid pace. As more published, methods needed for placing these in an ecological evolutionary context. Phages difficult to study by phylogenetic methods, because they exchange genes regularly, no single gene is conserved across all phages. Here, we demonstrate how gene-level networks can provide high-resolution view of genetic diversity offer novel perspective...
<ns3:p>Single-cell sequencing technologies offer unprecedented resolution to inspect transcriptomes and generate critical biological insights. As the number of cells cell types increase in single-cell studies, effort required analyze data surges dramatically, especially when comparative explorations need be performed on large datasets with different various sample attributes, such as clinical samples from age ancestry groups. Due sequential nature analysis, many steps involving multiple...
Background. How host-symbiont interactions coevolve between mutualism and parasitism depends on the ecology of system genetic physiological constraints organisms involved. Theory often predicts that greater reliance horizontal transmission favors increased costs infection may result in more virulent parasites or less beneficial mutualists. We set out to understand transitions by evolving filamentous bacteriophage M13 its host Escherichia coli . Results. The effect phage bacterial fitness...
Bacterial surveys of the vaginal and bladder human microbiota have revealed an abundance many similar bacterial taxa. As was once thought to be sterile, complex interactions between microbes within yet characterized. To initiate this process, we begun sequencing isolates, including clinically relevant genus Gardnerella. Herein, present genomic sequences four Gardnerella strains isolated from bladders women with symptoms urgency urinary incontinence; these are first genomes produced niche....
Mutualism is ubiquitous in nature and plays an integral role most communities. To predict the eco-evolutionary dynamics of mutualism it critical to extend classic pair-wise analysis include additional species. We investigated effect adding a third species spatially structured environment. tested hypotheses that selection for costly excretions focal population (i) decreases when exploiter added (ii) increases mutualist relative scenario. assayed acting on Salmonella enterica exchanges...
Lactobacillus species play a key role in the health of urinary tract. For instance, crispatus and L. jensenii have been found to inhibit uropathogenic Escherichia coli growth. While is typically only within microbiota women without lower tract symptoms (LUTS), has both with LUTS. With recent introduction new mulieris , several strains were reclassified as based upon gene marker average nucleotide identity. We took phylogenomic comparative genomic approach ascertain genetic determinants these...
Bacteriophages (phages) play a key role in shaping microbial communities, including those of the human body. Phages are abundant members urogenital tract, most often persisting through lysogenic life cycle as prophages integrated within genomes their bacterial hosts. While numerous studies microbiota have focused on member this niche–Lactobacillus species–very little is known about Lactobacillus phages. Focusing jensenii strains from urinary we identified related to previously characterized...
Filamentous phages establish chronic infections in their bacterial hosts, and new are secreted by infected bacteria for multiple generations, typically without causing host death. Often, these viruses integrate host's genome co-opting the XerCD recombinase system. In several cases, also encode genes that increase virulence plants animals. Here, we describe a filamentous phage, UPϕ901, which originally found integrated clinical isolate of Escherichia coli from urine. UPϕ901 closely related...
Abstract Appendicitis is one of the most common abdominal emergencies globally, yet little understood about inflammatory mechanisms or potential drivers disease. Neutrophil inflammation and increased cytokine expression such as IL-6 IL-8 are hallmarks appendicitis inflammation. However, early histological studies identified T B cell infiltration during appendicitis, providing support for adaptive immune activation well, although this has never been investigated in depth. We hypothesized that...
Abstract Response to checkpoint blockade immunotherapy (CBI) is not universal, partly due a wide variation in baseline immune cell infiltration the tumor microenvironment (TME). One mechanism contributing this variability cell-intrinsic activation of β-catenin signaling pathway, which has previously been shown result non-T cell-inflamed TME. Constitutive resulted reduced Batf3-lineage dendritic (cDC1) recruitment, leading T and loss anti-CTLA-4+anti-PD-L1 therapeutic efficacy. Efforts target...
Abstract Checkpoint blockade therapies have transformed the landscape of cancer care. Durable clinical responses been observed in a subset patients. However, many patients do not respond, and understanding mechanisms that determine tumor resistant to checkpoint drugs could potentially benefit more Ferroptosis is relatively newly described form regulated cell death distinct from apoptosis necroptosis. Recently, T cell-promoted ferroptosis was shown be an anti-tumor mechanism targeting this...
Abstract Bacteriophages are the most abundant and diverse biological entities on planet, new phage genomes being discovered at a rapid pace from metagenomes. As more novel, uncultured published, tools needed for placing these in an ecological evolutionary context. Phages difficult to study with phylogenetic methods, because they exchange genes regularly, no single gene is conserved across all phages. Instead, genome-level networks have been used group similar viruses into clusters taxonomy....
A pangenome is the collection of all genes found in a set related genomes. For microbes, these genomes are often different strains same species, and offers means to compare gene content variation with differences phenotypes, ecology, phylogenetic relatedness. Though most frequently applied bacteria, there growing interest adapting analysis bacteriophages. However, working phage presents new challenges. First, families under-sampled, homologous viruses can be difficult identify. Second,...
<div>Abstract<p>Immune checkpoint blockade is therapeutically successful for many patients across multiple cancer types. However, immune-related adverse events (irAE) frequently occur and can sometimes be life threatening. It critical to understand the immunologic mechanisms of irAEs with goal finding novel treatment targets. Herein, we report our analysis tissues from irAE dermatitis using multiparameter immunofluorescence (IF), spatial transcriptomics, RNA <i>in...
Supplementary Data from Checkpoint Blockade–Induced Dermatitis and Colitis Are Dominated by Tissue-Resident Memory T Cells Th1/Tc1 Cytokines