A5075572708- Microbial Natural Products and Biosynthesis
- Genomics and Phylogenetic Studies
- Plant Pathogenic Bacteria Studies
- Antibiotic Resistance in Bacteria
- Monoclonal and Polyclonal Antibodies Research
- RNA and protein synthesis mechanisms
- Receptor Mechanisms and Signaling
- Neuropeptides and Animal Physiology
- Bacterial biofilms and quorum sensing
- Bacterial Genetics and Biotechnology
- Burkholderia infections and melioidosis
- Mass Spectrometry Techniques and Applications
- Biochemical and Structural Characterization
- Alkaloids: synthesis and pharmacology
- Metabolomics and Mass Spectrometry Studies
- Immunotherapy and Immune Responses
- Cell Adhesion Molecules Research
- Parasite Biology and Host Interactions
- Glycosylation and Glycoproteins Research
- Essential Oils and Antimicrobial Activity
- Marine Sponges and Natural Products
- CRISPR and Genetic Engineering
Princeton University
2016-2021
Harvey Mudd College
2020
While bacterial genomes typically contain numerous secondary metabolite biosynthetic gene clusters, only a small fraction of these are expressed at any given time. The remaining majority is inactive or silent, and methods that awaken them would greatly expand our repertoire bioactive molecules. We recently devised new approach for identifying inducers silent clusters proposed the clinical antibiotic trimethoprim acted as global activator metabolism in Burkholderia thailandensis. Herein, we...
Abstract Integrins αvβ6 and αvβ8 in the tumor microenvironment (TME) have been shown to activate immunosuppressive TGF-β, which serves as an important mechanism for immune checkpoint inhibitor resistance a range of tumors. In this study, we demonstrate utility lasso peptides versatile scaffolds designing new therapeutics. A series highly potent selective dual αvβ6/8 inhibitors were engineered through combination epitope scanning, computational design, directed evolution. Several analogs,...
Abstract Lasso peptides exhibit a unique lariat-like knotted structure imparting exceptional stability and thus show promise as therapeutic agents that target cell-surface receptors. One such receptor is the human endothelin ET B receptor, which implicated in challenging cancers with poor immunotherapy responsiveness. The Streptomyces -derived lasso peptide, RES-701-3, selective inhibitor for compelling candidate development. However, meager production from genetically recalcitrant host has...
Significance Low-dose antibiotics can activate the expression of otherwise silent biosynthetic loci, but mechanisms underlying this phenomenon are poorly understood. Our results reveal several classes molecules that globally induce secondary metabolite biogenesis in model bacterium Burkholderia thailandensis . We illuminate mechanism induction one these elicitors, β-lactam piperacillin, and uncover oxidative stress as a new input initiates synthesis virulence factor malleicyprol. The finding...
Sarcophyton glaucum is one of the most abundant and chemically studied soft corals with over 100 natural products reported in literature, primarily cembrane diterpenoids. Yet, wide variation chemistry observed from S. past 50 years has led to its reputation as a capricious producer bioactive metabolites. Recent molecular phylogenetic analysis revealed that not single species but complex at least seven genetically distinct distinguishable using traditional taxonomic criteria. We hypothesized...
Abstract An alternative solution to the cyclical development of new antibiotics is concept disarming pathogens without affecting their growth, thereby eliminating selective pressures that lead resistant phenotypes. Here, we have employed our previously developed HiTES methodology identify one such compound against ESKAPE pathogen Pseudomonas aeruginosa . Rather than induce silent biosynthetic gene clusters, used suppress actively expressed virulence genes. By screening a library 770...
Abstract Lasso peptides exhibit a unique lariat-like knotted structure imparting exceptional stability and thus show promise as therapeutic agents that target cell-surface receptors. One such receptor is the human endothelin ET B receptor, which implicated in challenging cancers with poor immunotherapy responsiveness. The Streptomyces -derived lasso peptide, RES-701-3, selective inhibitor for compelling candidate development. However, meager production from genetically recalcitrant host has...