9 results on '"Lin, ChieYu"'
Search Results
2. VLDLR and ApoER2 are receptors for multiple alphaviruses
- Author
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Clark, Lars E., Clark, Sarah A., Lin, ChieYu, Liu, Jianying, Coscia, Adrian, Nabel, Katherine G., Yang, Pan, Neel, Dylan V., Lee, Hyo, Brusic, Vesna, Stryapunina, Iryna, Plante, Kenneth S., Ahmed, Asim A., Catteruccia, Flaminia, Young-Pearse, Tracy L., Chiu, Isaac M., Llopis, Paula Montero, Weaver, Scott C., and Abraham, Jonathan
- Published
- 2022
- Full Text
- View/download PDF
3. VLDLR and ApoER2 are receptors for multiple alphaviruses
- Author
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Clark, Lars E., Clark, Sarah A., Lin, ChieYu, Liu, Jianying, Coscia, Adrian, Nabel, Katherine G., Yang, Pan, Neel, Dylan V., Lee, Hyo, Brusic, Vesna, Stryapunina, Iryna, Plante, Kenneth S., Ahmed, Asim A., Catteruccia, Flaminia, Young-Pearse, Tracy L., Chiu, Isaac M., Llopis, Paula Montero, Weaver, Scott C., and Abraham, Jonathan
- Subjects
Mice ,Multidisciplinary ,Receptors, LDL ,viruses ,Alphaviruses ,Animals ,Mosquito Vectors ,Sindbis Virus ,Virus-host interactions ,Ligands ,Semliki forest virus ,Article ,LDL-Receptor Related Proteins - Abstract
Alphaviruses, like many other arthropod-borne viruses, infect vertebrate species and insect vectors separated by hundreds of millions of years of evolutionary history. Entry into evolutionarily divergent host cells can be accomplished by recognition of different cellular receptors in different species, or by binding to receptors that are highly conserved across species. Although multiple alphavirus receptors have been described1–3, most are not shared among vertebrate and invertebrate hosts. Here we identify the very low-density lipoprotein receptor (VLDLR) as a receptor for the prototypic alphavirus Semliki forest virus. We show that the E2 and E1 glycoproteins (E2–E1) of Semliki forest virus, eastern equine encephalitis virus and Sindbis virus interact with the ligand-binding domains (LBDs) of VLDLR and apolipoprotein E receptor 2 (ApoER2), two closely related receptors. Ectopic expression of either protein facilitates cellular attachment, and internalization of virus-like particles, a VLDLR LBD–Fc fusion protein or a ligand-binding antagonist block Semliki forest virus E2–E1-mediated infection of human and mouse neurons in culture. The administration of a VLDLR LBD–Fc fusion protein has protective activity against rapidly fatal Semliki forest virus infection in mouse neonates. We further show that invertebrate receptor orthologues from mosquitoes and worms can serve as functional alphavirus receptors. We propose that the ability of some alphaviruses to infect a wide range of hosts is a result of their engagement of evolutionarily conserved lipoprotein receptors and contributes to their pathogenesis., Studies using viral coat glycoproteins show that alphaviruses can enter cells via the very low-density lipoprotein receptor (VLDLR) and apolipoprotein E receptor 2 (ApoER2), members of an evolutionarily conserved family of lipoprotein receptors.
- Published
- 2021
4. The nucleolar protein Esf2 interacts directly with the DExD/H box RNA helicase, Dbp8, to stimulate ATP hydrolysis
- Author
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Granneman, Sander, Lin, ChieYu, Champion, Erica A., Nandineni, Madhusudan R., Zorca, Cornelia, and Baserga, Susan J.
- Published
- 2006
5. Utility of Histologic and Histochemical Screening for 16S Ribosomal RNA Gene Sequencing of Formalin-Fixed, Paraffin-Embedded Tissue for Bacterial Endocarditis
- Author
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Solomon, Isaac H, primary, Lin, Chieyu, additional, Horback, Katharine L, additional, Kanjilal, Sanjat, additional, Rojas-Rudilla, Vanesa, additional, Brigl, Manfred, additional, Laga, Alvaro C, additional, Lindeman, Neal I, additional, and Padera, Robert F, additional
- Published
- 2019
- Full Text
- View/download PDF
6. CAR-T Cell Therapies From the Transfusion Medicine Perspective
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Fesnak, Andrew, primary, Lin, ChieYu, additional, Siegel, Don L., additional, and Maus, Marcela V., additional
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- 2016
- Full Text
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7. STAT3-iNOS Signaling Mediates EGFRvIII-Induced Glial Proliferation and Transformation.
- Author
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Puram, Sidharth V., Yeung, Caleb M., Jahani-Asl, Arezu, Lin, Chieyu, de la Iglesia, Nuria, Konopka, Genevieve, Jackson-Grusby, Laurie, and Bonni, Azad
- Subjects
CELLULAR signal transduction ,NEUROGLIA ,CELL proliferation ,CELL transformation ,GLIOBLASTOMA multiforme ,TRANSCRIPTION factors ,EPIDERMAL growth factor - Abstract
Malignant gliomas, including glioblastoma multiforme, constitute the mostcommonand aggressive primary brain tumors in adults. The transcription factor signal transducer and activator of transcription 3 (STAT3) plays an essential role in glioblastoma pathogenesis downstream of the major oncogenic protein epidermal growth factor receptor variant III (EGFRvIII). However, the critical gene targets of STAT3 that mediate EGFRvIII-induced glial transformation have remained unknown. Here, we identify inducible nitric oxide synthase (iNOS) as a novel target gene of STAT3 in EGFRvIII-expressing mouse astrocytes. Endogenous STAT3 occupies the endogenous iNOS promoter and stimulates iNOS transcription in EGFRvIII-expressing astrocytes. STAT3 does not appear to control iNOS transcription in astrocytes deficient in the major glioblastoma tumor suppressor protein phosphatase and tensin homolog (PTEN), suggesting that STAT3 regulates iNOS transcription specifically in EGFRvIII-expressing astrocytes. Importantly, inhibition of iNOS by distinct approaches, including knockdown by RNA interference, reduces cell population growth and invasiveness of EGFRvIII-expressing astrocytes. In addition, upon iNOS knockdown or administration of a small-molecule inhibitor of iNOS, EGFRvIII-expressing astrocytes form smaller tumors in vivo. These findings suggest that inhibition of iNOS may have potential therapeutic value for EGFRvIII-activated brain tumors. [ABSTRACT FROM AUTHOR]
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- 2012
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8. Characterization and Optimization of the CRISPR/Cas System for Applications in Genome Engineering
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Lin, ChieYu
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Genome editing ,CRISPR-Cas ,Molecular Biology ,Cas9 - Abstract
The ability to precisely manipulate the genome in a targeted manner is fundamental to driving both basic science research and development of medical therapeutics. Until recently, this has been primarily achieved through coupling of a nuclease domain with customizable protein modules that recognize DNA in a sequence-specific manner such as zinc finger or transcription activator-like effector domains. Though these approaches have allowed unprecedented precision in manipulating the genome, in practice they have been limited by the reproducibility, predictability, and specificity of targeted cleavage, all of which are partially attributable to the nature of protein-mediated DNA sequence recognition. It has been recently shown that the microbial CRISPR-Cas system can be adapted for eukaryotic genome editing. Cas9, an RNA-guided DNA endonuclease, is directed by a 20-nt guide sequence via Watson-Crick base-pairing to its genomic target. Cas9 subsequently induces a double-stranded DNA break that results in targeted gene disruption through non-homologous end-joining repair or gene replacement via homologous recombination. Finally, the RNA guide and protein nuclease dual component system allows simultaneous delivery of multiple guide RNAs (sgRNA) to achieve multiplex genome editing with ease and efficiency. The potential effects of off-target genomic modification represent a significant caveat to genome editing approaches in both research and therapeutic applications. Prior work from our lab and others has shown that Cas9 can tolerate some degree of mismatch with the guide RNA to target DNA base pairing. To increase substrate specificity, we devised a technique that uses a Cas9 nickase mutant with appropriately paired guide RNAs to efficiently inducing double-stranded breaks via simultaneous nicks on both strands of target DNA. As single-stranded nicks are repaired with high fidelity, targeted genome modification only occurs when the two opposite-strand nicks are closely spaced. This double nickase approach allows for marked reduction of off-target genome modification while maintaining robust on-target cleavage efficiency, making a significant step towards addressing one of the primary concerns regarding the use of genome editing technologies. The ability to multiplex genome engineering by simply co-delivering multiple sgRNAs is a versatile property unique to the CRISPR-Cas system. While co-transfection of multiple guides is readily feasible in tissue culture, many in vivo and therapeutic applications would benefit from a compact, single vector system that would allow robust and reproducible multiplex editing. To achieve this, we first generated and functionally validated alternate sgRNA architectures to characterize the structure-function relationship of the Cas9 protein with the sgRNA in DNA recognition and cleavage. We then applied this knowledge towards the development and optimization of a tandem synthetic guide RNA (tsgRNA) scaffold that allows for a single promoter to drive expression of a single RNA transcript encoding two sgRNAs, which are subsequently processed into individual active sgRNAs.
- Published
- 2014
9. Developmental Origins of Aggressive Medulloblastoma
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Lin, Chieyu and Jackson-Grusby, Laurie Lynne
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Biology ,Cellular biology ,Cancer biology ,Cancer stem cells ,Developmental Field Cancerization ,Medulloblastoma - Abstract
Medulloblastomas represent a heterogeneous group of cerebellar tumors that constitute the most frequent primary pediatric solid malignancy. Molecular characterization of these tumors have led to the understanding that distinctsubtypes possess characteristic properties such as gene expression profile, histological classification, and degree of dissemination that are predictive of disease progression and prognosis. Fractionation of primary medulloblastomas has led to the appreciation of brain tumor stem cells (BTSC) that may be driving the more aggressive and malignant disease. However, the developmental origins of these cells as well as the influences of early mutations in tumor suppressors on development and tumorigenesisremain unclear. My work is geared towards understanding the impact of mutations in the key tumor suppressor genes Ptc1 and p53 on medulloblastoma formation. I first identified key differences in neural stem cell marker expression that distinguish between Ptc1 and Ptc1;p53 medulloblastomas, demonstrating that the Ptc1;p53 genotype may pre-dispose to a more malignant, stem-like tumor. Through the use of a somatic mosaic model, we describe a synergistic interaction between Ptc1 haploinsufficiency and p53 deficiency leading to developmental seeding of the cerebellar field by pre-malignant cells and term this phenomenon “developmental field cancerization.” Interestingly, we observed this premalignant colonization in the cerebellarstem cell compartment as well, resulting in an aberrant population of self-renewing cells. Upon loss-of-heterozygosity at the Ptc1 locus, the Ptc;p53 animals alone develop robust cerebellar tumorsthat possess a definable stem-like population of cells that can re-initiate metastatic secondary tumors. These findings demonstrate how early mutationsin the tumor suppressor genes, such as Ptc1 and p53, may lead to stem cell field cancerization and play an important role in determining future tumor character and prognosis.
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- 2013
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