A5076398738- Antibiotic Resistance in Bacteria
- Computational Drug Discovery Methods
- Tuberculosis Research and Epidemiology
- Receptor Mechanisms and Signaling
- Bacterial Genetics and Biotechnology
- Cardiac electrophysiology and arrhythmias
- Gut microbiota and health
- Evolution and Genetic Dynamics
- Mycobacterium research and diagnosis
- Spaceflight effects on biology
- Mechanical Circulatory Support Devices
- RNA and protein synthesis mechanisms
- Microbial Metabolic Engineering and Bioproduction
- Pharmaceutical and Antibiotic Environmental Impacts
- Breast Cancer Treatment Studies
- Bioinformatics and Genomic Networks
- Advanced Breast Cancer Therapies
- Estrogen and related hormone effects
- COVID-19 epidemiological studies
- Clostridium difficile and Clostridium perfringens research
- Bacterial biofilms and quorum sensing
- Cardiovascular Issues in Pregnancy
- Ion channel regulation and function
- Ion Transport and Channel Regulation
- Health, Environment, Cognitive Aging
Rutgers, The State University of New Jersey
2021-2025
Johns Hopkins Hospital
2025
Bloomberg (United States)
2025
Rutgers New Jersey Medical School
2021-2024
Taipei City Hospital
2024
Johnson University
2022-2024
Massachusetts Institute of Technology
2014-2019
Broad Institute
2017-2019
Harvard University
2015
Boston University
2014
Significance Substantial knowledge exists about how antibiotics interfere with core bacterial processes by binding to specific targets. Recently it has become appreciated that blocking these functions alters cellular redox state, and perturbations may contribute the lethality of antibiotics. In this work we explore whether antibiotic treatment bacteria affects oxidative stress role such in antibiotic-mediated killing. We find dynamically alter respiration induce lethal levels intracellular...
Bacteriostatic and bactericidal antibiotic treatments result in two fundamentally different phenotypic outcomes--the inhibition of bacterial growth or, alternatively, cell death. Most antibiotics inhibit processes that are major consumers cellular energy output, suggesting treatment may have important downstream consequences on metabolism. We hypothesized the specific metabolic effects bacteriostatic contribute to their overall efficacy. leveraged opposing phenotypes drugs combination...
Although metabolism plays an active role in antibiotic lethality, resistance is generally associated with drug target modification, enzymatic inactivation, and/or transport rather than metabolic processes. Evolution experiments of Escherichia coli rely on growth-dependent selection, which may provide a limited view the landscape. We sequenced and analyzed E. adapted to representative antibiotics at increasingly heightened states. This revealed various underappreciated noncanonical genes,...
Drug-resistant strains of Mycobacterium tuberculosis are a major global health problem. Resistance to the front-line antibiotic isoniazid is often associated with mutations in katG-encoded bifunctional catalase-peroxidase. We hypothesise that perturbed KatG activity would generate collateral vulnerabilities isoniazid-resistant katG mutants, providing potential pathway targets combat resistance. Whole genome CRISPRi screens, transcriptomics, and metabolomics were used genome-wide map cellular...
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....
Downstream metabolic events can contribute to the lethality of drugs or agents that interact with a primary cellular target. In bacteria, production reactive oxygen species (ROS) has been associated lethal effects variety stresses including bactericidal antibiotics, but relative contribution this oxidative component cell death depends on factors. Experimental evidence suggested unresolvable DNA problems caused by incorporation oxidized nucleotides into nascent followed incomplete base...
Nucleotide metabolism plays a central role in bacterial physiology, producing the nucleic acids necessary for DNA replication and RNA transcription. Recent studies demonstrate that nucleotide also proactively contributes to antibiotic-induced lethality pathogens disruptions antibiotic treatment failure clinic. As antimicrobial resistance continues grow unchecked, new approaches are needed study molecular mechanisms responsible efficacy. Here we review emerging technologies poised transform...
Abstract H37Rv is the most widely used Mycobacterium tuberculosis strain, and its genome globally as M. reference sequence. Here, we present Bact-Builder, a pipeline that uses consensus building to generate complete accurate bacterial sequences apply it three independently cultured sequenced aliquots of single laboratory stock. Two 4,417,942 base-pair long assemblies are 100% identical, with third differing by nucleotide. Compared existing reference, new sequence contains ~6.4 kb additional...
Traumatic brain injury (TBI) produces excessive glutamate, leading to excitotoxicity via the activation of glutamate receptors. Postsynaptic density scaffold proteins have crucial roles in mediating signal transduction from receptors their downstream mediators. Therefore, studies on mechanisms underlying regulation by can uncover new treatments for TBI. Here, we demonstrated that postsynaptic protein Homer 1a was neuroprotective against TBI vitro and vivo, this neuroprotection associated...
Abstract Chimeric Antigen Receptor (CAR) T-cell therapy is a highly effective treatment for B-cell malignancies but limited in use due to clinically significant hyperinflammatory toxicities. Understanding the pathophysiologic mechanisms which mediate these toxicities can help identify novel management strategies. Here we report vitro model of macrophage-endothelial interface study effects CAR T-cell-induced cytokine storm. Using this model, demonstrate that macrophage-mediated inflammation...
High mobility group box B1 (HMGB1)-receptor for advanced glycation endproducts (RAGE) axis has been previously known to be involved in carcinogenesis and development of multiple malignancies. Some studies have confirmed that Ethyl pyruvate (EP), a potent inhibitor HMGB1, exerts the therapeutic effects on metastatic live tumor from gastric cancer. However, possible molecular mechanisms EP gallbladder cancer (GBC) need further explored. In present study, human GBC cell lines (GBC-SD SGC-996)...