A5028905727- Cancer-related gene regulation
- CAR-T cell therapy research
- CRISPR and Genetic Engineering
- Gold and Silver Nanoparticles Synthesis and Applications
- RNA and protein synthesis mechanisms
- Advanced Nanomaterials in Catalysis
- Nanocluster Synthesis and Applications
- Muscle Physiology and Disorders
- Membrane-based Ion Separation Techniques
- RNA modifications and cancer
- Neuroinflammation and Neurodegeneration Mechanisms
- Biochemical effects in animals
- Spectroscopy and Quantum Chemical Studies
- Virus-based gene therapy research
- Protein Hydrolysis and Bioactive Peptides
- Ion Transport and Channel Regulation
- Advanced biosensing and bioanalysis techniques
- Evolution and Genetic Dynamics
- Epigenetics and DNA Methylation
- Protein Degradation and Inhibitors
- Renin-Angiotensin System Studies
- nanoparticles nucleation surface interactions
- Geographic Information Systems Studies
- Cancer Research and Treatments
- Nanoparticles: synthesis and applications
McGill University
2020-2023
The University of Texas MD Anderson Cancer Center
2019-2022
Jewish General Hospital
2022
The University of Texas at San Antonio
2014-2016
PRMT5 is an arginine methyltransferase that accounts for the vast majority of symmetric methylation in cells. exerts its function when complexed with MEP50/WDR77. This activity often elevated cancer cells and correlates poor prognosis, making a therapeutic target. To investigate signaling pathway to identify genes whose loss-of-function sensitizes inhibition, we performed CRISPR/Cas9 genetic screen presence inhibitor. We identified known components writer/reader including itself,...
Despite the success of immune checkpoint inhibitor (ICI) therapy for cancer, resistance and relapse are frequent. Combination therapies expected to enhance response rates overcome this resistance. Herein, we report that combining PRMT7 inhibition with ICI induces a strong anti-tumor T cell immunity restrains tumor growth in vivo by increasing infiltration. PRMT7-deficient B16.F10 melanoma exhibits increased expression genes interferon pathway, antigen presentation, chemokine signaling....
DDX5, XRN2, and PRMT5 have been shown to resolve DNA/RNA hybrids (R-loops) at RNA polymerase II transcription termination sites few genomic loci. Herein, we perform genome-wide R-loop mapping using classical immunoprecipitation high-throughput sequencing (DRIP-seq) of loci regulated by PRMT5. We observed hundreds thousands gains losses transcribed in DDX5-, XRN2-, PRMT5-deficient U2OS cells. were characteristic highly genes located gene-rich regions, whereas low-density gene areas. shared...
Abstract High-throughput CRISPR-Cas9 knockout screens using a tiling-sgRNA design permit in situ evaluation of protein domain function. Here, to facilitate de novo identification essential domains from such screens, we propose ProTiler, computational method for the robust mapping CRISPR hyper-sensitive (CKHS) regions, which refer regions associated with strong sgRNA dropout effect screens. Applied published tiling screen dataset, ProTiler identifies 175 CKHS 83 proteins. Of these more than...
Abstract The specificity of CRISPR/Cas9 genome editing is largely determined by the sequences guide RNA (gRNA) and targeted DNA, yet sequence-dependent rules underlying off-target effects are not fully understood. To systematically explore sequence determinants governing specificity, here we describe a dual-target system to measure relative cleavage rate between off- on-target (off-on ratios) 1902 gRNAs on 13,314 synthetic target sequences, reveal set involving 2 factors in off-targeting: 1)...
Non-small cell lung cancer (NSCLC) is the deadliest worldwide. Therapeutic progress stagnate, highlighting complexity to replicate NSCLC in preclinical models. Drug discovery studies rely mostly on cells two-dimension (2D), which poorly predict drug efficacy patients. There a growing interest three-dimensional (3D) models, such as 3D spheroids, better model tumor phenotype and improve therapeutic prediction. However, comprehensive view of culture methods impact transcriptomes, epigenomes...
The role of RNA binding proteins in regulating the phagocytic and cytokine-releasing functions microglia is unknown. Here, we show that deficient for QUAKING (QKI) protein have increased proinflammatory cytokine release defects processing phagocytosed cargo. Splicing analysis reveals a QKI microexon networks Rho GTPase pathway. We an increase RhoA activation cytokines QKI-deficient are repressed by treating with Rock kinase inhibitor. During cuprizone diet, mice inefficient at supporting...
RNA-binding proteins play important roles in X-linked intellectual disability (XLID). In this study, we investigate the contribution of XLID-associated RBMX neuronal differentiation. We show that RBMX-depleted cells exhibit aberrant activation p53 pathway. Moreover, identify RGG/RG motif is methylated by protein arginine methyltransferase 5 (PRMT5), and regulates assembly with SRSF1 splicing factor into higher-order complexes. Depletion or disruption RBMX/SRSF1 complex PRMT5-depleted reduces...
Computing the ligand-protein binding affinity (or Gibbs free energy) with chemical accuracy has long been a challenge for which many methods/approaches have developed and refined various successful applications. False positives and, even more harmful, false negatives still are common occurrence in practical Inevitable all approaches errors force field parameters we obtain from quantum mechanical computation and/or empirical fittings intra- inter-molecular interactions. These propagate to...
Na<sup>+</sup>ions promote aggregation of gold nanoparticles functionalized with negatively charged, short ligands.
Nanometer-sized gold particles (AuNPs) are of peculiar interest because their behaviors in an aqueous solution sensitive to changes environmental factors including the size and shape solute ions. In order determine these important characteristics, we performed all-atom molecular dynamics simulations on icosahedral Au144 nanoparticles each coated with a homogeneous set 60 thiolates (4-mercaptobenzoate, pMBA) eight solutions having ions varying sizes shapes (Na(+), K(+), tetramethylamonium...
Among the thirteen types of water channel proteins, aquaporins (AQPs), which play various essential roles in human physiology, AQP4 is richly expressed cells central nervous system and implicated pathological conditions such as brain edema. Therefore, researchers have been looking for ways to inhibit AQP4's water-conducting function. Many small molecules investigated their interactions with residues that form entry vestibule on extracellular side interruption waters entering into conducting...
Remyelination failure in multiple sclerosis leads to progressive demyelination and inflammation, resulting neurodegeneration clinical decline. Microglia are innate immune cells that can acquire a regenerative phenotype promote remyelination, yet little is known about the regulators controlling microglia activation. Herein, using cuprizone (CPZ)-diet induced de- remyelination mice model, we identify PRMT1 as driver for MHC-associated population required central nervous system. The loss of...
In skeletal muscle, muscle stem cells (MuSC) are the main responsible for regeneration upon injury. diseased it would be therapeutically advantageous to replace defective MuSCs, or rejuvenate them with drugs enhance their self-renewal and ensure long-term regenerative potential. One limitation of replacement approach has been inability efficiently expand MuSCs ex vivo, while maintaining stemness engraftment abilities. Herein, we show that inhibition type I protein arginine methyltransferases...
Abstract Despite the success of immune checkpoint inhibitor (ICI) therapy in different cancers, resistance and relapses are frequent. Thus, combination therapies expected to enhance response rates overcome ICIs. Herein, we report that combining protein arginine methyltransferase 7 (PRMT7) inhibition with ICIs triggers a strong anti-tumor T cell immunity restrains tumor growth vivo by increasing infiltration. Consistently, TCGA database analysis showed an inverse correlation between PRMT7...
Abstract In skeletal muscle, muscle stem cells (MuSC) are the main responsible for regeneration upon injury. diseased it would be therapeutically advantageous to replace defective MuSCs, or rejuvenate them with drugs enhance their self-renewal and ensure long-term regenerative potential. One limitation of replacement approach has been inability efficiently expand MuSCs ex vivo, while maintaining stemness engraftment abilities. Herein, we show that inhibition type I protein arginine...
In skeletal muscle, muscle stem cells (MuSC) are the main responsible for regeneration upon injury. diseased it would be therapeutically advantageous to replace defective MuSCs, or rejuvenate them with drugs enhance their self-renewal and ensure long-term regenerative potential. One limitation of replacement approach has been inability efficiently expand MuSCs ex vivo, while maintaining stemness engraftment abilities. Herein, we show that inhibition type I protein arginine methyltransferases...