A5043240332- RNA Research and Splicing
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Cancer-related molecular mechanisms research
- Immunotherapy and Immune Responses
- interferon and immune responses
- Lymphoma Diagnosis and Treatment
- RNA regulation and disease
- CAR-T cell therapy research
- Cancer-related gene regulation
- Acute Myeloid Leukemia Research
- Viral Infections and Immunology Research
- Immune Cell Function and Interaction
- Glycosylation and Glycoproteins Research
- RNA Interference and Gene Delivery
- Genomics and Chromatin Dynamics
- T-cell and B-cell Immunology
- Molecular Biology Techniques and Applications
- Cancer Genomics and Diagnostics
- Cytokine Signaling Pathways and Interactions
- Influenza Virus Research Studies
- Viral Infections and Vectors
- Pluripotent Stem Cells Research
- Mosquito-borne diseases and control
- Advanced biosensing and bioanalysis techniques
University of Pennsylvania
2016-2025
California University of Pennsylvania
2022-2025
University of Louisville
2022
Pediatrics and Genetics
2017
Institute of Molecular Biology and Biophysics
2015
The University of Texas Southwestern Medical Center
2002-2011
Southwestern Medical Center
2007-2009
Merck (Germany)
2005
University of California, San Francisco
2000-2001
Howard Hughes Medical Institute
2000-2001
The CD19 antigen, expressed on most B-cell acute lymphoblastic leukemias (B-ALL), can be targeted with chimeric antigen receptor-armed T cells (CART-19), but relapses epitope loss occur in 10% to 20% of pediatric responders. We detected hemizygous deletions spanning the locus and de novo frameshift missense mutations exon 2 some relapse samples. However, we also discovered alternatively spliced mRNA species, including one lacking 2. Pull-down/siRNA experiments identified SRSF3 as a splicing...
Alternative splicing (AS) can critically affect gene function and disease, yet mapping variations remains a challenge. Here, we propose new approach to define quantify mRNA in units of local (LSVs). LSVs capture previously defined types alternative as well more complex transcript variations. Building the first genome wide map from twelve mouse tissues, find constitute over 30% tissue dependent specific protein families. We show prevalence is conserved humans identify hundreds that are brain...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic, resulting millions of infections and deaths with few effective interventions available. Here, we demonstrate that SARS-CoV-2 evades interferon (IFN) activation in epithelial cells, delayed response bystander cells. Since pretreatment IFNs can block viral infection, reasoned pharmacological innate immune pathways could control infection. To identify potent antiviral agonists, screened panel 75 microbial...
The Drosophila doublesex female-specific splicing enhancer consists of two classes regulatory elements, six 13-nucleotide repeat sequences, and a single purine-rich element (PRE). Here, we show that the proteins Transformer (Tra) 2 (Tra2) recruit different members SR family factors to repeats PRE. complexes formed on in HeLa cell extract consist Tra, Tra2, protein 9G8. Kc extract, Tra Tra2 RBP1 repeats. These are arranged specific order repeats, with at 5' end each repeat, 3' end. Although...
The role of alternative splicing (AS) in eliciting immune responses is poorly understood. We used quantitative AS microarray profiling to survey changes during activation Jurkat cells, a leukemia-derived T-cell line. Our results indicate that ∼10%–15% the profiled exons undergo >10% change inclusion level activation. majority genes displaying differential levels are distinct from set transcript levels. These two gene sets also have overlapping yet functional roles. For example, show...
Regulated alternative splicing of doublesex (dsx) pre-mRNA requires a enhancer designated the dsx repeat element (dsxRE) that contains six copies 13-nucleotide sequence. Previous studies have shown activity dsxRE regulators Transformer (Tra) and 2 (Tra2), one or more members SR family general factors. In this paper we identify purine-rich (PRE) sequence within dsxRE, show functionally synergizes with sequences. vitro binding PRE is required for specific Tra2 to Tra proteins bind...
Multiple isoforms of the protein tyrosine phosphatase CD45 are expressed on surface human T cells.Interestingly, expression these has been shown to vary significantly upon T-cell activation.In this report, we describe a novel cell line-based model system in which can mimic activation-induced alternative splicing observed primary cells.Of many proximal signaling events induced by stimulation, show that activation kinase C and Ras important for switch toward exclusion variable exons, whereas...
The formation and execution of a productive immune response requires the maturation competent T cells robust change in cellular activity upon antigen challenge. Such changes function depend on regulated alterations to protein expression. Previous research has focused defining transcriptional that regulate expression during T-cell stimulation. Here, we globally analyze another critical process gene regulation stimulation, alternative splicing. Specifically, use RNA-seq profiling identify 178...
Influenza A virus is a major human pathogen with genome comprised of eight single-strand, negative-sense, RNA segments. Two viral segments, NS1 and M, undergo alternative splicing yield several proteins including NS1, NS2, M1 M2 proteins. However, the mechanisms or players involved in these segments have not been fully studied. Here, by investigating interacting partners function cellular protein NS1-binding (NS1-BP), we revealed novel segment. Using proteomics approach, identified complex...
Caspase-9 has two splice variants, pro-apoptotic caspase-9a and anti-apoptotic caspase-9b, which are regulated by RNA trans-factors associated with exon 3 of caspase-9 pre-mRNA (C9/E3). In this study, we identified hnRNP U as an trans-factor C9/E3. Down-regulation led to a decrease in the caspase-9a/9b mRNA ratio, demonstrating novel enhancing function. Importantly, bound specifically C9/E3 at cis-element previously reported binding site for splicing repressor, L. Phosphorylated L interfered...