A5003630594- CRISPR and Genetic Engineering
- Pluripotent Stem Cells Research
- Renal and related cancers
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Epigenetics and DNA Methylation
- Animal Genetics and Reproduction
- RNA Interference and Gene Delivery
- HIV Research and Treatment
- interferon and immune responses
- Virus-based gene therapy research
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- SARS-CoV-2 and COVID-19 Research
- Nitric Oxide and Endothelin Effects
- RNA modifications and cancer
- Cancer, Hypoxia, and Metabolism
- Chromosomal and Genetic Variations
- Molecular Biology Techniques and Applications
- MicroRNA in disease regulation
- Cytokine Signaling Pathways and Interactions
- Histone Deacetylase Inhibitors Research
- RNA Research and Splicing
- Advanced biosensing and bioanalysis techniques
- Animal Virus Infections Studies
- vaccines and immunoinformatics approaches
VIR Biotechnology (United States)
2021-2025
Vir Biotechnology (Switzerland)
2022-2025
University of California, Los Angeles
2010-2024
University of San Francisco
2024
University of California, San Francisco
2022
Broad Center
2016-2018
Black AIDS Institute
2012-2015
University of California System
2010
Much attention has focussed on the conversion of human pluripotent stem cells (PSCs) to a more naïve developmental status. Here we provide method for resetting via transient histone deacetylase inhibition. The protocol is effective across multiple PSC lines and can proceed without karyotype change. Reset be expanded feeders with doubling time around 24 h. WNT inhibition stabilises process. transcriptome reset diverges markedly from that primed PSCs shares features inner cell mass (ICM)....
ABSTRACT Sotrovimab (VIR-7831) and VIR-7832 are dual action monoclonal antibodies (mAbs) targeting the spike glycoprotein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). were derived from a parent antibody (S309) isolated memory B cells 2003 (SARS-CoV) survivor. Both mAbs contain an “LS” mutation in Fc region to prolong serum half-life. In addition, encodes GAALIE that has been shown previously evoke CD8+ T-cells context vivo viral infection. neutralize wild-type variant...
X chromosome inactivation (XCI) serves as a paradigm for RNA-mediated regulation of gene expression, wherein the long non-coding RNA XIST spreads across in cis to mediate silencing chromosome-wide. In female naive human pluripotent stem cells (hPSCs), is dispersed configuration, and XCI does not occur, raising questions about XIST's function. We found that induces dampening X-linked expression hPSCs. Surprisingly, also targets specific autosomal regions, where it repressive chromatin changes...
Applications of embryonic stem cells (ESCs) require faithful chromatin changes during differentiation, but the fate X chromosome state in differentiating ESCs is unclear. Female human ESC lines either carry two active chromosomes (XaXa), an Xa and inactive with or without XIST RNA coating (XiXIST+Xa;XiXa), eroded Xi (XeXa) where no longer expresses has partially reactivated. Here, we established XiXa, XeXa, XaXa followed their differentiation. Surprisingly, found that pre-existing primed...
The role of nitric oxide (NO) in cancer has been controversial and is based on the levels NO responsiveness tumor type. It remains unclear whether can inhibit epithelial to mesenchymal transition (EMT) cells. EMT induction mediated, part, by constitutive activation metastasis-inducer transcription factor, Snail be inhibited metastasis-suppressor Raf-1 kinase inhibitor protein (RKIP) E-cadherin. transcriptionally regulated NF-κB turn, represses RKIP transcription. Hence, we hypothesized that...
Down-regulation of the HIV-1 coreceptor CCR5 holds significant potential for long-term protection against in patients. Using humanized bone marrow/liver/thymus (hu-BLT) mouse model which allows investigation human hematopoietic stem/progenitor cell (HSPC) transplant and immune system reconstitution as well infection, we previously demonstrated stable inhibition expression systemic lymphoid tissues via transplantation HSPCs genetically modified by lentiviral vector transduction to express...
X chromosome inactivation (XCI) is a developmental program of heterochromatin formation that initiates during early female mammalian embryonic development and maintained through lifetime cell divisions in somatic cells. Despite identification the crucial long non-coding RNA Xist involvement specific chromatin modifiers establishment maintenance inactive (Xi), interference with known pathways only partially reactivates Xi once silencing has been established. Here, we studied ATF7IP (MCAF1),...
We described earlier a dual-combination anti-HIV type 1 (HIV-1) lentiviral vector (LVsh5/C46) that downregulates CCR5 expression of transduced cells via RNAi and inhibits HIV-1 fusion cell surface membrane-anchored C46 antiviral peptide. This combinatorial approach has two points inhibition for R5-tropic is also active against X4-tropic HIV-1. Here, we utilize the humanized bone marrow, liver, thymus (BLT) mouse model to characterize in vivo efficacy LVsh5/C46 (Cal-1) engineer cellular...
DNA methylation is important for the maintenance of silent state genes on inactive X chromosome (Xi). Here, we screened siRNAs and chemicals that reactivate an Xi-linked reporter in presence 5-aza-2'-deoxycytidine (5-aza-2'-dC), inhibitor methyltransferase 1, at a concentration that, its own, not sufficient Xi-reactivation. We found inhibition ribonucleotide reductase (RNR) induced expression reporter. RNR potentiated effect 5-aza-2'-dC by enhancing incorporation, thereby decreasing levels...
Respiratory viruses represent a major global health burden. Although these have different life cycles, they may depend on common host genetic factors, which could be targeted by broad-spectrum host-directed therapies. We used genome-wide CRISPR screens and advanced data analytics to map network of genes that support infection nine human respiratory [influenza A virus, parainfluenza rhinovirus, syncytial coronavirus (HCoV)-229E, HCoV-NL63, HCoV-OC43, Middle East syndrome–related coronavirus,...
RNA interference is a natural antiviral mechanism that could be harnessed to combat SARS-CoV-2 infection by targeting and destroying the viral RNA. We identified potent lipophilic small interfering (siRNA) conjugates highly conserved regions of outside spike-encoding region capable achieving ≥3-log reduction. Serial passaging studies demonstrated two-siRNA combination prevented development resistance compared single siRNA approach. Viral treatment occurred due emergence point mutations at...
SUMMARY Much attention has focussed on conversion of human pluripotent stem cells (PSC) to a more naive developmental status. Here we provide method for resetting via transient histone deacetylase inhibition. The protocol is effective across multiple PSC lines and can proceed without karyotype change. Reset be expanded feeders with doubling time around 24 hours. WNT inhibition stabilises the process. transcriptome reset diverges markedly from primed shares features inner cell mass (ICM)....
Abstract Nitric oxide (NO) has been shown to mediate contrasting effects on tumorigenesis i.e. at low levels NO is pro-tumorigenic and high anti-tumorigenic. Recent studies revealed that treatment of tumor cell lines with donors significantly inhibited growth survival pathways such as the constitutively activated NF-κB. Tumor cells NF-κB were reported have capacity initiate metastatic cascade via induction epithelial mesenchymal transition (EMT). The EMT phenotype characterized by decreased...