A5085428833- RNA Research and Splicing
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Genetic Neurodegenerative Diseases
- Eicosanoids and Hypertension Pharmacology
- Pharmacogenetics and Drug Metabolism
- Mitochondrial Function and Pathology
- Cancer-related molecular mechanisms research
- Tissue Engineering and Regenerative Medicine
- RNA regulation and disease
- CRISPR and Genetic Engineering
- Drug Transport and Resistance Mechanisms
- MicroRNA in disease regulation
- Inflammatory mediators and NSAID effects
- Estrogen and related hormone effects
- Liver Disease Diagnosis and Treatment
- Molecular Biology Techniques and Applications
- Metalloenzymes and iron-sulfur proteins
- Liver physiology and pathology
- Endoplasmic Reticulum Stress and Disease
- Genetics, Bioinformatics, and Biomedical Research
- Cardiomyopathy and Myosin Studies
- Pancreatic function and diabetes
- Lipid metabolism and biosynthesis
- Single-cell and spatial transcriptomics
University of Illinois Urbana-Champaign
2016-2025
Chan Zuckerberg Initiative (United States)
2024-2025
Chan Zuckerberg Biohub San Francisco
2024
Chan Zuckerberg Biohub Chicago
2024
Cellular Research (United States)
2020
University of Illinois System
2018
Baylor College of Medicine
2008-2015
McMaster University
2015
The University of Texas Health Science Center at Houston
2003-2008
Apath (United States)
2008
From a large-scale screen using splicing microarrays and RT-PCR, we identified 63 alternative (AS) events that are coordinated in 3 distinct temporal patterns during mouse heart development. More than half of these transitions evolutionarily conserved between chicken. Computational analysis the introns flanking enriched motifs including binding sites for CUGBP ETR-3-like factors (CELF), muscleblind-like (MBNL) Fox proteins. We show CELF proteins down-regulated >10-fold development, MBNL1...
Alternative cleavage and polyadenylation (APA) results in mRNA isoforms containing different 3' untranslated regions (3'UTRs) and/or coding sequences. How core cleavage/polyadenylation (C/P) factors regulate APA is not well understood. Using siRNA knockdown coupled with deep sequencing, we found that several C/P can play significant roles 3'UTR-APA. Whereas Pcf11 Fip1 enhance usage of proximal poly(A) sites (pAs), CFI-25/68, PABPN1 PABPC1 promote distal pAs. Strong cis element biases were...
Alternative splicing transitions have been identified recently as a conserved component of vertebrate heart remodeling during postnatal development. Here we report that the targeted deletion Dicer, specifically in adult mouse myocardium, reveals role microRNAs (miRNAs) regulating networks and maintaining programs. We demonstrate direct for miR-23a/b dramatic down-regulation CUGBP ETR-3-like factor (CELF) proteins regulate nearly half developmentally regulated heart. These findings define...
Although major genetic networks controlling early liver specification and morphogenesis are known, the mechanisms responsible for postnatal hepatic maturation poorly understood. Here we employ global analyses of mouse transcriptome to demonstrate that remodelling is accompanied by large-scale transcriptional post-transcriptional transitions cell-type-specific temporally coordinated. Combining detailed expression with gain- loss-of-function studies, identify epithelial splicing regulatory...
The adult liver has an exceptional ability to regenerate, but how it maintains its specialized functions during regeneration is unclear. Here, we used partial hepatectomy (PHx) in tandem with single-cell transcriptomics track cellular transitions and heterogeneities of ∼22,000 cells through the initiation, progression, termination phases mouse regeneration. Our results uncovered that, following PHx, a subset hepatocytes transiently reactivates early-postnatal-like gene expression program...
Abstract Regulation of RNA processing contributes profoundly to tissue development and physiology. Here, we report that serine-arginine-rich splicing factor 1 (SRSF1) is essential for hepatocyte function survival. Although SRSF1 mainly known its many roles in mRNA metabolism, it also crucial maintaining genome stability. We show acute liver damage the setting targeted deletion mice associated with excessive formation deleterious RNA–DNA hybrids (R-loops), which induce DNA damage. Combining...
Cardiac dysfunction is the second leading cause of death in myotonic dystrophy type 1 (DM1), primarily because arrhythmias and cardiac conduction defects. A screen more than 500 microRNAs (miRNAs) a DM1 mouse model identified 54 miRNAs that were differentially expressed heart. More 80% exhibited downregulation toward embryonic expression pattern showed DM1-specific response. total 20 22 tested also significantly downregulated human heart tissue. We demonstrate many these are direct MEF2...
The rate of protein synthesis in the adult heart is one lowest mammalian tissues, but it increases substantially response to stress and hypertrophic stimuli through largely obscure mechanisms. Here, we demonstrate that regulated expression cytosolic poly(A)-binding 1 (PABPC1) modulates synthetic capacity heart. We uncover a poly(A) tail-based regulatory mechanism dynamically controls PABPC1 cardiomyocytes thereby titrates cellular translation developmental cues. Our findings identify as...
Severe alcoholic hepatitis (SAH) is a deadly liver disease without an effective medical therapy. Although SAH mortality known to correlate with hepatic accumulation of immature cells, why this occurs and how it causes death are unclear. Here, we demonstrate that expression epithelial splicing regulatory protein 2 (ESRP2), RNA-splicing factor maintains the nonproliferative, mature phenotype adult hepatocytes, was suppressed in both human various mouse models parallel severity alcohol...
Traumatic brain injury is known to cause several secondary effects, which lead multiple organ dysfunction syndrome. An acute systemic inflammatory response seems play an integral role in the development of such complications providing potential for massive injury. We show that a contusion rat causes large migration cells (especially macrophages and neutrophils) major airways alveolar spaces at 24 h post-injury, associated with enhanced pulmonary leukotriene B 4 (LTB ) production within lung....
Two insults often underlie a variety of eye diseases including glaucoma, optic atrophy, and retinal degeneration—defects in mitochondrial function aberrant Rhodopsin trafficking. Although defects are associated with oxidative stress, they have not been linked to In an unbiased forward genetic screen designed isolate mutations that cause photoreceptor degeneration, we identified nuclear-encoded gene, ppr, homolog human LRPPRC. We found ppr is required for protection against light-induced...
Developing highly active, multivalent ligands as therapeutic agents is challenging because of delivery issues, limited cell permeability, and toxicity. Here, we report intrinsically cell-penetrating that target the trinucleotide repeat DNA RNA in myotonic dystrophy type 1 (DM1), interrupting disease progression two ways. The oligomeric are designed based on repetitive structure with recognition moieties alternating bisamidinium groove binders to provide an amphiphilic polycationic structure,...
By using complementary DNA sequences as surface ligands, we selectively allow two individual diffusing "dual-color" carbon dots to interact in situ and vitro. Spontaneous nanoscale oxidation of surface-abundant nitroso-/nitro-functionalities leads distinctly colored (CD) which are isolated by polarity driven chromatographic separation. Green- red-emitting (gCD rCD) were decorated single-stranded DNAs produce a marked increase the fluorescence emission respective dots. Mutual colloidal...
Abstract Foam cells in atheroma are engorged with lipid droplets (LDs) that contain esters of regulatory lipids whose metabolism remains poorly understood. LD-associated hydrolase (LDAH) has a lipase structure and high affinity for LDs foam cells. Using knockout transgenic mice both sexes, here we show LDAH inhibits atherosclerosis development promotes stable lesion architectures. Broad targeted lipidomic analyzes primary macrophages comparative profiling identified broad impact on...