A5006205806- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- Single-cell and spatial transcriptomics
- RNA modifications and cancer
- Acute Myeloid Leukemia Research
- Chronic Myeloid Leukemia Treatments
- Genomics and Chromatin Dynamics
- T-cell and B-cell Immunology
- Mosquito-borne diseases and control
- Extracellular vesicles in disease
- Immunotherapy and Immune Responses
- Viral Infections and Vectors
- Histone Deacetylase Inhibitors Research
- CRISPR and Genetic Engineering
- Microtubule and mitosis dynamics
- DNA Repair Mechanisms
- Gene expression and cancer classification
- Cancer-related molecular mechanisms research
- Multiple Myeloma Research and Treatments
- Genetic and Kidney Cyst Diseases
- Viral Infections and Outbreaks Research
- Molecular Biology Techniques and Applications
- Autoimmune and Inflammatory Disorders Research
- Chromosomal and Genetic Variations
- Chronic Lymphocytic Leukemia Research
University of Colorado Anschutz Medical Campus
2021-2025
University of Colorado Denver
2016-2025
University of Missouri–St. Louis
2013
Venetoclax-based therapy can induce responses in approximately 70% of older previously untreated patients with acute myeloid leukemia (AML). However, up-front resistance as well relapse following initial response demonstrates the need for a deeper understanding mechanisms. In present study, we report that to venetoclax +azacitidine AML correlate closely developmental stage, where phenotypically primitive is sensitive, but monocytic more resistant. Mechanistically, resistant has distinct...
<ns4:p>Assignment of cell types from single-cell RNA sequencing (scRNA-seq) data remains a time-consuming and error-prone process. Current packages for identity assignment use limited reference often have rigid structure requirements. We developed the clustifyr R package to leverage several external types, including gene expression profiles assign likely using scRNA-seq, bulk RNA-seq, microarray data, or signature lists. benchmark various parameters correlation-based approach implement list...
Paused RNA polymerase II (Pol II) that piles up near most human promoters is the target of mechanisms control entry into productive elongation. Whether paused Pol a stable or dynamic remains unresolved. We report 5' throughout genome turned over within 2 min. This process revealed under hypertonic conditions prevent recruitment to promoters. turnover requires cell viability but not prevented by inhibiting transcription elongation, suggesting it mediated at level termination. When initiation...
<ns4:p>New tools for reproducible exploratory data analysis of large datasets are important to address the rising size and complexity genomic data. We developed valr R package enable flexible efficient interval analysis. leverages new available in ”tidyverse”, including dplyr. Benchmarks show it performs similar BEDtools can be used interactive analyses incorporated into existing pipelines.</ns4:p>
Assignment of cell types from single-cell RNA sequencing (scRNA-seq) data remains a time-consuming and error-prone process. Current packages for identity assignment use limited reference often have rigid structure requirements. We developed the clustifyr R package to leverage several external types, including gene expression profiles assign likely using scRNA-seq, bulk RNA-seq, microarray data, or signature lists. benchmark various parameters correlation-based approach implement list...
Abstract The restrictor, ZC3H4/WDR82, is the major termination factor for antisense transcription from bidirectional promoters, but its mechanism poorly understood. We report that ZC3H4/WDR82 co-purifies with PP1 phosphatase and nuclear targeting subunit, PNUTS, which binds directly to WDR82 subunit of restrictor. AlphaFold predicts a quaternary complex, PPWZ, in P P1-associated NUTS Z C3H4 both contact W DR82. To investigate role protein dephosphorylation PPWZ activity, we expressed...
The detection of foreign antigens in vivo has relied on fluorescent conjugation or indirect read-outs such as antigen presentation. In our studies, we found that these widely used techniques had several technical limitations have precluded a complete picture trafficking retention across lymph node cell types. To address limitations, developed ‘molecular tracking device’ to follow the distribution, acquisition, and node. Utilizing an conjugated nuclease-resistant DNA tag, acting combined...
Multiple lines of evidence indicate that the AP-2 transcription factor family has an important regulatory function in human craniofacial development. Notably, mutations TFAP2A, gene encoding AP-2α, have been identified patients with Branchio-Oculo-Facial Syndrome (BOFS). BOFS is autosomal-dominant trait commonly presents facial clefting, eye defects and branchial skin anomalies. Examination multiple cases suggested either simple haploinsufficiency or more complex genetic causes for BOFS,...
The restrictor, ZC3H4/WDR82, terminates antisense transcription from bidirectional promoters, but its mechanism is poorly understood. We report that ZC3H4/WDR82 immunoprecipitate with PP1 phosphatase and nuclear targeting subunit, PNUTS, which binds to WDR82. AlphaFold predicts a complex of PP1/PNUTS restrictor where both PNUTS ZC3H4 contact A substrate trap, PP1H66K-PNUTS, comprising inactive fused the C-terminus antagonizes mediated termination whereas PP1WT-PNUTS has less effect...
Internal ribosome entry sites (IRESs) are powerful model systems to understand how the translation machinery can be manipulated by structured RNAs and for exploring inherent features of function. The intergenic region (IGR) IRESs from Dicistroviridae family viruses that bind directly initiate co-opting elongation cycle. These require an RNA pseudoknot mimics a codon-anticodon interaction contains conformationally dynamic loop. We explored role this loop found both length sequence essential...
Manipulation of protein stability with ligand-regulated degron fusions is a powerful method for investigating gene function. We developed selectable cassette easy C-terminal tagging endogenous human proteins the E. coli dihydrofolate reductase (eDHFR) using CRISPR/Cas9 genome editing. This permits high-efficiency recovery correct integration events an in-frame self-cleaving 2A peptide and puromycin resistance gene. PCR amplified donor eDHFR fragments 100 bases homology on each end are...
Summary A nabaena variabilis ATCC 29413 fixes nitrogen in specialized cells called heterocysts using either a Mo ‐nitrogenase or V ‐nitrogenase. structural genes, vnfDGK , as well vnfEN form an operon with ava4025 located upstream of vnfDG that is repressed by fixed and . The ‐ vnfDGKEN under the control ‐repressible promoter nearly 600 bp Levels transcript were about 500‐fold higher than first gene operon. This may be result RNA processing at site 87 was initially identified transcription...
Adaptive angiogenesis is necessary for tissue repair, however, it may also be associated with the exacerbation of injury and development chronic disease. In these studies, we demonstrate that lung mesenchymal vascular progenitor cells (MVPC) modulate adaptive via lineage trace, depletion MVPC, modulation β-catenin expression. Single cell sequencing confirmed MVPC as multipotential progenitors, thus, genetic resulted in alveolar simplification reduced angiogenesis. Following endothelial...
Infection with chikungunya virus (CHIKV) causes disruption of draining lymph node (dLN) organization, including paracortical relocalization B cells, loss the cell-T cell border, and lymphocyte depletion that is associated infiltration LN inflammatory myeloid cells. Here, we found that, during first 24 hours infection, CHIKV RNA accumulated in MARCO-expressing lymphatic endothelial cells (LECs) both floor medullary sinuses. The accumulation viral was a switch to an antiviral gene expression...
The biological purpose of Integrator and RNA polymerase II (RNAPII) promoter-proximal pausing remains uncertain. Here, we show that loss INTS6 in human cells results increased interaction RNAPII with proteins can mediate its dissociation from the DNA template, including CRL3
About 5% of B cells in healthy mice and humans are allelically or isotypically included hence co-express two different antibodies. In mice, dual antibody (B2R) expand with systemic autoimmunity, autoreactive non-autoreactive antibodies, participate immune responses, but this phenomenon is strain dependent. This study was developed goals: 1) to establish the contribution TLR IFN receptor signaling development germinal center that express antibodies MRL/lpr mice; 2) determine whether B2R...