A5030454201- Tuberculosis Research and Epidemiology
- Mycobacterium research and diagnosis
- RNA and protein synthesis mechanisms
- Bioinformatics and Genomic Networks
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Respiratory Support and Mechanisms
- Brucella: diagnosis, epidemiology, treatment
- Bacterial Genetics and Biotechnology
- Cancer therapeutics and mechanisms
- Asthma and respiratory diseases
- Bacteriophages and microbial interactions
- Genomics and Phylogenetic Studies
- Microbial Metabolic Engineering and Bioproduction
- Computational Drug Discovery Methods
- Cardiovascular and exercise physiology
- Immune Response and Inflammation
- Neuroinflammation and Neurodegeneration Mechanisms
- Burkholderia infections and melioidosis
- Gene expression and cancer classification
- Zebrafish Biomedical Research Applications
- RNA modifications and cancer
- Cancer, Hypoxia, and Metabolism
- vaccines and immunoinformatics approaches
- Antibiotic Resistance in Bacteria
- Biochemical and Molecular Research
University of Washington
2018-2024
Infectious Disease Research Institute
2016-2024
Baotou Medical College
2020-2024
Harbor–UCLA Medical Center
2009-2023
Seattle Children's Hospital
2019-2023
UCLA Medical Center
2009-2023
Qinghai Institute for Endemic Diease Prevention and Control
2020
Center for Infectious Disease Research
2015-2018
Institute for Systems Biology
2013-2017
University of Illinois Urbana-Champaign
2010-2017
Abstract Mycobacterium tuberculosis (MTB) infects 30% of all humans and kills someone every 20–30 s. Here we report genome-wide binding for ~80% predicted MTB transcription factors (TFs), assayed global expression following induction each TF. The DNA-binding network consists ~16,000 events from 154 TFs. We identify >50 TF-DNA consensus motifs >1,150 promoter-binding directly associated with proximal gene regulation. An additional ~4,200 are in promoter windows represent strong...
Abstract Background Mycobacterium tuberculosis senses and responds to the shifting hostile landscape of host. To characterize underlying intertwined gene regulatory network governed by approximately 200 transcription factors M. , we have assayed global transcriptional consequences overexpressing each factor from an inducible promoter. Results We cloned overexpressed 206 in identify signature each. identified 9,335 183 factors, providing evidence regulation for 70% genome. These signatures...
Approximately 5% of patients with drug-susceptible tuberculosis have a relapse after 6 months first-line therapy, as do approximately 20% 4 short-course therapy. We postulated that by analyzing pretreatment isolates Mycobacterium obtained from who subsequently had or were cured, we could determine any correlations between the minimum inhibitory concentration (MIC) drug below standard resistance breakpoint and risk treatment.
The length and complexity of tuberculosis (TB) therapy, as well the propensity Mycobacterium to develop drug resistance, are major barriers global TB control efforts. M. is known have ability enter into a drug-tolerant state, which may explain many these impediments treatment. We identified mechanism genetically encoded but rapidly reversible tolerance in caused by transient frameshift mutations homopolymeric tract (HT) 7 cytosines (7C) glpK gene. Inactivating associated with 7C HT produce...
Abstract Mechanisms underlying variability in transmission of Mycobacterium tuberculosis strains remain undefined. By characterizing high and low M.tuberculosis mice, we show here that strain induce rapid IL-1R-dependent alveolar macrophage migration from the space into interstitium this action is key to subsequent temporal events early dissemination bacteria lymph nodes, Th1 priming, granulomatous response bacterial control. In contrast, nodes significantly impeded infection with strain;...
We sought to develop procedures for computerized analysis of long-term, high-resolution activity monitoring data that allow accurate assessment the time course levels suitable use in chronic obstructive pulmonary disease (COPD) patients. Twenty-two COPD patients utilizing long-term oxygen recruited from 5 sites Clinical Research Network wore a triaxial accelerometer (RT3, Stayhealthy, Monrovia, CA) during waking hours over 14-day period. Computerized algorithms were composed allowing...
Mycobacterium tuberculosis senses and responds to the shifting hostile landscape of host. To characterize underlying intertwined gene regulatory network governed by approximately 200 transcription factors M. tuberculosis, we have assayed global transcriptional consequences overexpressing each factor from an inducible promoter. We cloned overexpressed 206 in identify signature each. identified 9,335 183 factors, providing evidence regulation for 70% genome. These signatures agree well with...
Mycobacterium tuberculosis (MTB) is the causative bacterium of tuberculosis, a disease responsible for over million deaths worldwide annually with growing number strains resistant to antibiotics. The development better therapeutics would greatly benefit from improved understanding mechanisms associated MTB responses different genetic and environmental perturbations. Therefore, we expanded genome-scale regulatory-metabolic model using Probabilistic Regulation Metabolism (PROM) framework. Our...
Abstract Spatial heterogeneity is a fundamental feature of the tumor microenvironment (TME), and tackling spatial in neoplastic metabolic aberrations critical for treatment. Genome-scale network models have been used successfully to simulate cancer networks. However, most use bulk gene expression data entire biopsies, ignoring TME. To account heterogeneity, we performed spatially-resolved modeling prostate microenvironment. We discovered novel malignant-cell-specific vulnerabilities...
Mycobacterium tuberculosis (MTB) is a pathogenic bacterium responsible for 12 million active cases of (TB) worldwide. The complexity and critical regulatory components MTB pathogenicity are still poorly understood despite extensive research efforts. In this study, we constructed the first systems-scale map transcription factor (TF) binding sites their target proteins in MTB. We FLAG-tagged overexpression constructs 206 TFs MTB, used ChIP-seq to identify genome-wide events surveyed global...
The rapid spread of multidrug-resistant strains has created a pressing need for new drug regimens to treat tuberculosis (TB), which kills 1.8 million people each year. Identifying been challenging due the slow growth pathogen
Brucellosis caused by Brucella melitensis is considered to be one of the most important zoonotic diseases in China. In this study, Conventional bio-typing, MLVA (multiple locus variable-number tandem repeat analysis), and WGS (whole-genome sequencing)-SNP (single nucleotide polymorphism) were used study genetic similarity B. northern southern China analyze its relationship with worldwide lineages. Currently, distribution species/biovars has obviously changed, become dominant species regions...
Gene regulatory and metabolic network models have been used successfully in many organisms, but inherent differences between them make networks difficult to integrate. Probabilistic Regulation Of Metabolism (PROM) provides a partial solution, it does not incorporate inference underperforms eukaryotes. We present an Integrated Deduced And (IDREAM) method that combines statistically inferred Environment Regulatory Influence Network (EGRIN) with the PROM framework create enhanced...
Introduction Mycobacterium tuberculosis (Mtb) is the causative agent of disease, greatest source global mortality by a bacterial pathogen. Mtb adapts and responds to diverse stresses, such as antibiotics, inducing transcriptional stress response regulatory programs. Understanding how when mycobacterial programs are activated could inform novel treatment strategies that hinder adaptation potentiate efficacy new existing drugs. Here, we sought define analyze modulate fitness under stress....
Background The biomarker discovery field is replete with molecular signatures that have not translated into the clinic despite ostensibly promising performance in predicting disease phenotypes. One widely cited reason lack of classification consistency, largely due to failure maintain from study study. This attributed variability data collected for same phenotype among disparate studies, technical factors unrelated phenotypes (e.g., laboratory settings resulting "batch-effects") and...
Abstract Multidrug-resistant tuberculosis (MDR-TB), defined as resistance to the first-line drugs isoniazid and rifampin, is a growing source of global mortality threatens control disease. The diarylquinoline bedaquiline has recently emerged highly efficacious drug against MDR-TB kills Mycobacterium by inhibiting mycobacterial ATP synthase. However, mechanisms underlying bedaquiline’s efficacy remain unknown. Here we investigate hyper-susceptibility in drug-resistant using systems biology...