A5033957374- RNA Research and Splicing
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Advanced Biosensing Techniques and Applications
- Advanced biosensing and bioanalysis techniques
- Monoclonal and Polyclonal Antibodies Research
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- RNA Interference and Gene Delivery
- Cancer-related molecular mechanisms research
- Biosensors and Analytical Detection
- Acute Myeloid Leukemia Research
- Nanofabrication and Lithography Techniques
Digital Proteomics (United States)
2024-2025
University of Arizona
2018-2023
Arizona State University
2019-2021
University of Phoenix
2021
StemCells (United States)
2018
Significance Pre-messenger RNA (pre-mRNA) splicing is a key regulatory step in gene expression. The reaction mediated by the spliceosome, dynamic complex comprising five small nuclear ribonucleoproteins (snRNPs), which assembles onto each intron multiple steps. We present detailed structural analysis and supporting functional data of an important protein–RNA interaction between human U1 U2 snRNP. Our structure shows that intrinsically disordered arginine-glycine (RGG/RG)–rich motif snRNP...
Drug discovery continues to face a staggering 90% failure rate, with many setbacks occurring during late-stage clinical trials. To address this challenge, there is an increasing focus on developing and evaluating new technologies enhance the "design" "test" phases of antibody-based drugs (e.g., monoclonal antibodies, bispecifics, CAR-T therapies, ADCs) biologics early preclinical development, goal identifying lead molecules higher likelihood success. Artificial intelligence (AI) becoming...
Studying protein interactions in high throughput (HTP) is critical for advancing many aspects of drug discovery, biomarker identification, and diagnostic development. However, existing methods producing functional libraries are costly, time-consuming, lack real-time kinetic screening capabilities. To address these limitations, we developed an automated platform HTP production a library proteins on biosensor surfaces, facilitating large-scale measurement interaction kinetics. This technology,...
Abstract Myeloid malignancies, including myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid are characterized by abnormal proliferation differentiation of hematopoietic stem progenitor cells (HSPCs). Reports on analysis bone marrow samples from patients have revealed a high incidence mutations in splicing factors early cell clones, but the mechanisms underlying transformation HSPCs harboring these remain unknown. Using ex vivo cultures primary human CD34+ as model,...
During splicing of pre-mRNA, 5′ and 3′ splice sites are brought within proximity by interactions between the pre-mRNA bound U1 U2 snRNPs, followed recruitment tri-snRNP for assembly mature spliceosome. Previously, we identified an interaction snRNP-specific protein SF3A1 stem–loop 4 (SL4) snRNA that occurs during early steps spliceosome assembly. Although harboring many annotated domains, lacks a canonical RNA binding domain. To identify U1-SL4 region in SF3A1, expressed amino-...
During spliceosome assembly, interactions that bring the 5′ and 3′ ends of an intron in proximity are critical for production mature mRNA. Here, we report synergistic roles stem-loops 3 (SL3) 4 (SL4) human U1 small nuclear RNA (snRNA) maintaining optimal snRNP function, formation cross-intron contact with U2 snRNP. We find SL3 SL4 bind distinct spliceosomal proteins combining a snRNA activity assay siRNA-mediated knockdown, demonstrate act through helicase UAP56 protein SF3A1, respectively....
During gene expression, the vital step of pre-mRNA splicing involves accurate recognition splice sites and efficient assembly spliceosomal complexes to join exons remove introns prior cytoplasmic export mature mRNA. Splicing efficiency can be altered by presence mutations at sites, influence trans-acting factors, or activity therapeutics. Here, we describe protocol for a cellular assay that applied monitoring any given exon. The uses an adaptable plasmid encoded 3-exon/2-intron minigene...
Abstract An automated proteomic platform for producing and screening an array of functional proteins on biosensor surfaces was developed to address the challenges measuring interaction kinetics in high throughput (HTP). This technology is termed Sensor-Integrated Proteome On Chip (SPOC®) which involves in-situ cell-free protein expression nano-liter volume wells (nanowells) directly from rapidly customizable arrays plasmid DNA, facilitating simultaneous capture-purification up 2400 unique...
The human U1 snRNA is encoded by a multigene family consisting of transcribed variants and defective pseudogenes. Many variant (vU1) snRNAs have been demonstrated to not only be but also processed the addition trimethylated guanosine cap, packaged into snRNPs, assembled spliceosomes; however, their capacity facilitate pre-mRNA splicing has, so far, tested. A recent systematic analysis genes identified 178 that are present in genome as either tandem arrays or single on multiple chromosomes....
During gene expression, the vital step of pre-mRNA splicing involves accurate recognition splice sites and efficient assembly spliceosomal complexes to join exons remove introns prior cytoplasmic export mature mRNA. Splicing efficiency can be altered by presence mutations at sites, influence trans-acting factors, or activity therapeutics. Here, we describe protocol for a cellular assay that applied monitoring any given exon. The uses an adaptable plasmid encoded 3-exon/2-intron minigene...
Abstract Tissue specific tumor neo-antigens and associated antigens (TAAs) play a pivotal role in immune system interaction with cancer cells. Mutated, alternately spliced, over-expressed, mis-folded abnormally post-translationally modified proteins may elicit responses that suppress development. As these are distinct from normal self-proteins they offer the possibility of serving as highly-specific biomarkers for early detection. TAAs increasingly being targeted priming response to...