A5011528491- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- Immune cells in cancer
- Gut microbiota and health
- Antimicrobial Peptides and Activities
- Tuberculosis Research and Epidemiology
- Mycobacterium research and diagnosis
- Tryptophan and brain disorders
- Antibiotic Resistance in Bacteria
- RNA and protein synthesis mechanisms
- Microbial Metabolism and Applications
- Evolution and Genetic Dynamics
- Bacterial Genetics and Biotechnology
- Biosimilars and Bioanalytical Methods
- Cancer, Stress, Anesthesia, and Immune Response
- Nanoplatforms for cancer theranostics
- Genomics and Phylogenetic Studies
- Infectious Diseases and Tuberculosis
- Cancer Research and Treatments
- Bird parasitology and diseases
- Advanced Biosensing Techniques and Applications
- Microbial Community Ecology and Physiology
- Probiotics and Fermented Foods
- Microbial Metabolic Engineering and Bioproduction
- Bioinformatics and Genomic Networks
Harvard University
2017-2024
Liverpool School of Tropical Medicine
2024
Nepal Medical College Teaching Hospital
2024
Massachusetts General Hospital
2024
Wellcome Trust
2024
Health and Human Development (2HD) Research Network
2024
Hospital for Tropical Diseases
2024
Oxford University Clinical Research Unit
2024
Center for Systems Biology
2024
Seres Therapeutics (United States)
2022-2024
Whole-genome sequencing (WGS) of bacterial isolates has become standard practice in many laboratories. Applications for WGS analysis include phylogeography and molecular epidemiology, using single nucleotide polymorphisms (SNPs) as the unit evolution. NASP was developed a reproducible method that scales well with hundreds to thousands data typically used comparative genomics applications. In this study, we demonstrate how compares other tools two real datasets one simulated dataset. Our...
ABSTRACT Infection with Mycobacterium tuberculosis causes a spectrum of outcomes; the majority individuals contain but do not eliminate infection, while small subset present primary active (TB) disease. This variability in infection outcomes is recapitulated at granuloma level within each host, such that some sites can be fully cleared others progress. Understanding TB requires new tools to deconstruct mechanisms underlying differences fate. Here, we use novel genome-encoded barcodes...
Abstract Gut-microbiota modulation shows promise in improving immune-checkpoint blockade (ICB) response; however, precision biomarker-driven, placebo-controlled trials are lacking. We performed a multicenter, randomized placebo-controlled, biomarker-stratified phase I trial patients with ICB-naïve metastatic melanoma using SER-401, an orally delivered Firmicutesenriched spore formulation. Fecal microbiota signatures were characterized at baseline; stratified by high versus low...
ABSTRACT The emergence of distinct populations Cryptococcus gattii in the temperate North American Pacific Northwest (PNW) was surprising, as this species previously thought to be confined tropical and semitropical regions. Beyond a new habitat niche, dominant emergent population displayed increased virulence caused primary pulmonary disease, opposed predominantly neurologic disease seen elsewhere. Whole-genome sequencing performed on 118 C. isolates, including PNW subtypes global diversity...
Undetected and untreated, low-levels of drug resistant (DR) subpopulations in clinical Mycobacterium tuberculosis (Mtb) infections may lead to development DR-tuberculosis, potentially resulting treatment failure. Current phenotypic DR susceptibility testing has a theoretical potential for 1% sensitivity, is not quantitative, requires several weeks complete. The use "single molecule-overlapping reads" (SMOR) analysis with next generation DNA sequencing determination ultra-rare target alleles...
Mixed microbial communities underpin important biotechnological processes such as biological wastewater treatment (BWWT). A detailed knowledge of community structure and function relationships is essential for ultimately driving these systems towards desired outcomes, e.g., the enrichment in organisms capable accumulating valuable resources during BWWT.
The widespread use of antibiotics has placed bacterial pathogens under intense pressure to evolve new survival mechanisms. Genomic analysis 51,229 Mycobacterium tuberculosis (Mtb)clinical isolates identified an essential transcriptional regulator, Rv1830, herein called resR for resilience as a frequent target positive (adaptive) selection. mutants do not show canonical drug resistance or tolerance but instead shorten the post-antibiotic effect, meaning that they enable Mtb resume growth...
ABSTRACT For centuries, cholera has been one of the most feared diseases. The causative agent Vibrio cholerae is a waterborne Gram-negative enteric pathogen eliciting severe watery diarrheal disease. In October 2010, seventh pandemic reached Haiti, country that had not experienced for more than century. By using whole-genome sequence typing and mapping strategies 116 serotype O1 strains from global sources, including 44 Haitian genomes, we present detailed reconstructed evolutionary history...
Abstract Microbial communities are complex and dynamic systems that primarily structured according to their members’ ecological niches. To investigate how niche breadth (generalist versus specialist lifestyle strategies) relates success, we develop apply an integrative workflow for the multi-omic analysis of oleaginous mixed microbial from a biological wastewater treatment plant. Time- space-resolved coupled metabolomic taxonomic analyses demonstrate community-wide lipid accumulation...
Nosocomial acquisition of Clostridium difficile is well documented, yet recent studies have highlighted the importance community acquired infections and identified associated reservoirs for this pathogen. Multiple implicated companion pets farm animals as possible sources C. in humans. To explore potential role pet dogs human we systematically collected canine fecal samples (n = 197) Flagstaff, AZ. Additionally, nineteen were at a local veterinary clinic from diarrheic dogs. We used these...
Abstract Viruses and plasmids (invasive mobile genetic elements (iMGEs)) have important roles in shaping microbial communities, but their dynamic interactions with CRISPR-based immunity remain unresolved. We analysed generation-resolved iMGE–host dynamics spanning one a half years consortium from biological wastewater treatment plant using integrated meta-omics. identified 31 bacterial metagenome-assembled genomes encoding complete CRISPR–Cas systems corresponding iMGEs. CRISPR-targeted...
Drug-resistant TB remains a public health challenge. Rifamycins are among the most potent anti-TB drugs. They known to target RpoB subunit of RNA polymerase; however, our understanding how rifamycin resistance is genetically encoded incomplete. Here we investigated rpoB genetic diversity and cross-resistance between two drugs rifampicin rifabutin. We performed WGS 1003 Mycobacterium tuberculosis clinical isolates determined MICs both agents on 7H10 agar using indirect proportion method....
Phenotypic antibiotic susceptibility testing in Mycobacterium tuberculosis is slow and cumbersome. Rapid molecular diagnostics promise to help guide therapy, but such assays rely on complete knowledge of the determinants altered susceptibility. Recent genomic studies antibiotic-resistant M. have identified several candidate loci beyond those already known contribute resistance; however, efforts provide experimental validation lagged. Our study identifies a gene (Rv0565c) that associated with...
Despite the existence of well-characterized, canonical mutations that confer high-level drug resistance to Mycobacterium tuberculosis (Mtb), there is evidence mechanisms are more complex than simple acquisition such mutations. Recent studies have shown Mtb can acquire non-canonical resistance-associated survival advantages in presence certain drugs, likely acting as stepping-stones for resistance. Rv2752c/rnj, encoding RNase J, disproportionately mutated drug-resistant clinical isolates....
Genomic dissection of antibiotic resistance in bacterial pathogens has largely focused on genetic changes conferring growth above a single critical concentration drug. However, reduced susceptibility to antibiotics—even below this breakpoint—is associated with poor treatment outcomes the clinic, including tuberculosis. Clinical strains Mycobacterium tuberculosis exhibit extensive quantitative variation but basis behind spectrum drug remains ill-defined. Through genome wide association study,...
CD8 T cells provide limited protection against Mycobacterium tuberculosis (Mtb) infection in the mouse model. As Mtb causes chronic mice and humans, we hypothesize that impairs cell responses as an immune evasion strategy. TB10.4 is immunodominant antigen people, nonhuman primates, mice, which encoded by esxH gene. In C57BL/6 30–50% of pulmonary recognize TB10.44−11 epitope. However, TB10.4-specific fail to Mtb-infected macrophages. We speculate elicits antigens are inefficiently presented...
Abstract Whole genome sequencing (WGS) of bacteria is becoming standard practice in many laboratories. Applications for WGS analysis include phylogeography and molecular epidemiology, using single nucleotide polymorphisms (SNPs) as the unit evolution. The Northern Arizona SNP Pipeline (NASP) was developed a reproducible pipeline that scales well with large amount data typically used comparative genomics applications. In this study, we demonstrate how NASP compares to other tools two real...
The pathogenicity of Mycobacterium tuberculosis depends upon its ability to catabolize host cholesterol. Upregulation the methylcitrate cycle (MCC) is required assimilate and detoxify propionyl-CoA, a cholesterol degradation product. transcription key genes prpC prpD in MCC activated by MtPrpR, member family prokaryotic factors whose structures modes action have not been clearly defined. We show that MtPrpR has novel overall structure directly binds CoA or short-chain acyl-CoA derivatives...
We develop data-driven algorithms to fully automate sensor fault detection in systems governed by underlying physics. The proposed machine learning method uses a time series of typical behavior approximate the evolution measurements interest linear time-invariant system. Given additional data from related sensors, Kalman observer is used maintain separate real-time estimate measurement interest. Sustained deviation between and detect anomalous behavior. A decision tree, informed integrating...
The bacterial determinants that facilitate Mycobacterium tuberculosis (Mtb) adaptation to the human host environment are poorly characterized. We have sought decipher pressures facing bacterium in vivo by assessing Mtb genes under positive selection clinical isolates. One of strongest targets genome is lldD2 , which encodes a quinone-dependent L-lactate dehydrogenase (LldD2) catalyzes oxidation lactate pyruvate. Lactate accumulation salient feature intracellular during infection and...
Abstract The Gram-negative beta-proteobacterium Zoogloea sp. LCSB751 (LMG 29444) was newly isolated from foaming activated sludge of a municipal wastewater treatment plant. Here, we describe its draft genome sequence and annotation together with general physiological genomic analysis, as the first sequenced representative genus. Moreover, gene expression in environment is described using metatranscriptomic data obtained same presented transcriptomic information demonstrate pronounced...