A5063313275- Genomics and Chromatin Dynamics
- S100 Proteins and Annexins
- Computational Drug Discovery Methods
- Fungal and yeast genetics research
- Chromosomal and Genetic Variations
- CAR-T cell therapy research
- Nanowire Synthesis and Applications
- Pneumonia and Respiratory Infections
- Antimicrobial Peptides and Activities
- Neonatal and Maternal Infections
- Streptococcal Infections and Treatments
- RNA and protein synthesis mechanisms
- Advanced biosensing and bioanalysis techniques
- Plant Molecular Biology Research
- Monoclonal and Polyclonal Antibodies Research
- DNA Repair Mechanisms
- Plant-Microbe Interactions and Immunity
- Transgenic Plants and Applications
- Immunotherapy and Immune Responses
- Chromatin Remodeling and Cancer
- Antimicrobial Resistance in Staphylococcus
- Genomics and Phylogenetic Studies
- Crystallography and molecular interactions
- CRISPR and Genetic Engineering
- Ubiquitin and proteasome pathways
University of Oregon
2019-2023
Fred Hutch Cancer Center
2017
University of Maryland, Baltimore
2012-2017
University of Baltimore
2013
Therapies based on immune cells have been applied for diseases ranging from cancer to diabetes. However, the viral and electroporation methods used create cytoreagents are complex expensive. Consequently, we develop targeted mRNA nanocarriers that simply mixed with reprogram them via transient expression. Here, describe three examples establish approach is simple generalizable. First, demonstrate delivering encoding a genome-editing agent can efficiently knock-out selected genes in...
ObjectivesOur objective was to evaluate and exploit a whole genome sequence (WGS) bioinformatics pipeline for predicting antimicrobial resistance capsular serotypes from invasive group B streptococci (iGBS).MethodsFor 1975 iGBS recovered during 2015 CDC's Active Bacterial Core surveillance, we compared predictions with broth dilution testing. Fifty-six isolates earlier surveillance were included testing β-lactams. Conventional serotyping WGS-based assignments 302 isolates.ResultsAll 28...
Our whole genome sequence (WGS) pipeline was assessed for accurate prediction of antimicrobial phenotypes. For 2316 invasive pneumococcal isolates recovered during 2015 we compared WGS data to broth dilution testing (BDT) 18 antimicrobials. 11 antimicrobials categorical discrepancies were assigned when WGS-predicted MICs and BDT predicted different categorizations susceptibility, intermediate resistance or resistance, ranging from 0.9% (tetracycline) 2.9% (amoxicillin). β-lactam antibiotics,...
Eukaryotic genomes are organized dynamically through the repositioning of nucleosomes. Isw2 is an enzyme that has been previously defined as a genome-wide, nonspecific nucleosome spacing factor. Here, we show instead acts obligately targeted remodeler in vivo physical interactions with sequence-specific factors. We demonstrate Isw2-recruiting factors use small and uncharacterized epitopes, which direct activity highly conserved acidic residues accessory protein Itc1. This interaction orients...
Molecular Dynamics simulations of the pentamidine-S100B complex, where two molecules pentamidine bind per monomer S100B, were performed in an effort to determine what properties would be desirable a pentamidine-derived compound as inhibitor for S100B. These predicted that increasing linker length allow single molecule span both binding sites on protein. The resulting compound, SBi4211 (also known heptamidine), was synthesized and experiments study its inhibition S100B performed. 1.65 Å X-ray...
MNase-seq (micrococcal nuclease sequencing) is used to map nucleosome positions in eukaryotic genomes study the relationship between chromatin structure and DNA-dependent processes. Current protocols require at least two days isolate nucleosome-protected DNA fragments. We have developed a streamlined protocol for S. cerevisiae other fungi which takes only three hours. Modified were wild mammalian cells. This method rapidly producing sequencing-ready footprints from several organisms makes...
Upon glucose starvation, S . cerevisiae shows a dramatic alteration in transcription, resulting wide-scale repression of most genes and activation some others. This coincides with an arrest cellular proliferation. A subset such cells enters quiescence, reversible non-dividing state. Here, we demonstrate that the conserved transcriptional corepressor Tup1 is critical for after depletion. We show Tup1-Ssn6 binds new targets upon depletion, where it remains as enter G0 phase cell cycle. In...
The drug pentamidine inhibits calcium-dependent complex formation with p53 ((Ca)S100B·p53) in malignant melanoma (MM) and restores tumor suppressor activity vivo. However, off-target effects associated this were problematic MM patients. Structure-activity relationship (SAR) studies therefore completed here 23 analogues, X-ray structures of (Ca)S100B·inhibitor complexes revealed that the C-terminus S100B adopts two different conformations, location Phe87 Phe88 being distinguishing feature...
S100A1 is a member of the S100 family Ca 2+ -binding proteins and regulates several cellular processes, including those involved in signaling cardiac skeletal muscle function. In Alzheimer's disease, brain overexpressed gives rise to disease pathologies, making it potential therapeutic target. The 2.25 Å resolution crystal structure -S100A1 solved here compared with structures other proteins, most notably S100B, which highly homologous S100-family that implicated progression malignant...
Regulation of chromatin structure is essential for controlling access DNA to factors that require association with specific sequences. Here we describe the development and validation engineered remodeling proteins (E-ChRPs) inducing programmable changes in nucleosome positioning by design. We demonstrate E-ChRPs function both vitro vivo specifically reposition target nucleosomes entire nucleosomal arrays. show induced, systematic over yeast Ume6 binding sites leads exclusion,...
Abstract Upon glucose starvation, S. cerevisiae shows a dramatic alteration in transcription, resulting wide-scale repression of most genes and activation some others. This coincides with an arrest cellular proliferation. A subset such cells enters quiescence, reversible non-dividing state. Here, we demonstrate that the conserved transcriptional corepressor Tup1 is critical for after depletion. We show Tup1-Ssn6 binds new targets upon depletion, where it remains as enter G0 phase cell cycle....
Abstract Eukaryotic DNA is packaged into nucleosomes, the smallest repeating unit of chromatin. The positions nucleosomes determine relative accessibility genomic DNA. Several protocols exist for mapping nucleosome in eukaryotic genomes order to study relationship between chromatin structure and DNA-dependent processes. These can be laborious and, at minimum, require two three days isolate nucleosome-protected fragments. We have developed a streamlined protocol from S. cerevisiae liquid...
Abstract Eukaryotic genomes are organized dynamically through the repositioning of nucleosomes. Isw2 is an enzyme that has been previously defined as a genome-wide, non-specific nucleosome spacing factor. Here, we show instead acts obligately targeted remodeler in vivo physical interactions with sequence-specific factors. We demonstrate Isw2-recruiting factors use small and uncharacterized epitopes, which direct activity highly conserved acidic residues accessory protein Itc1. This...
Abstract The organization of chromatin – including the positions nucleosomes and binding other proteins to DNA helps define transcriptional profiles in eukaryotic organisms. While techniques like ChIP-Seq MNase-Seq can map protein-DNA nucleosome localization separately, assays designed simultaneously capture interactions produce a detailed picture landscape. Most that monitor protein rely on antibodies, which often exhibit nonspecific binding, and/or addition bulky adducts DNA-binding being...
Abstract The S100 family of proteins displays no enzymatic activity but has been shown to play roles in an array biological functions such as calcium homeostasis, cellular growth, inflammation, and metabolism. influence these homodimeric is mediated through protein-protein interactions a typically dependent manner aberrant expression linked variety cancers, cardiomyopathies, neurological disorders. Of particular interest, S100B highly over-expressed many including malignant melanoma (MM). In...