A5027278009- CRISPR and Genetic Engineering
- Immune Cell Function and Interaction
- RNA and protein synthesis mechanisms
- HIV Research and Treatment
- Advanced biosensing and bioanalysis techniques
- Amyloidosis: Diagnosis, Treatment, Outcomes
- T-cell and B-cell Immunology
- Synthesis and Catalytic Reactions
- Insect symbiosis and bacterial influences
- Catalytic C–H Functionalization Methods
- Sarcoidosis and Beryllium Toxicity Research
- Reproductive System and Pregnancy
- Dermatological and Skeletal Disorders
- Innovation and Socioeconomic Development
- Virus-based gene therapy research
- Monoclonal and Polyclonal Antibodies Research
- Crystallography and molecular interactions
- Pluripotent Stem Cells Research
- Hemoglobinopathies and Related Disorders
- RNA Interference and Gene Delivery
- Protein Degradation and Inhibitors
- RNA regulation and disease
- Plant Virus Research Studies
- Asymmetric Hydrogenation and Catalysis
- Metal-Catalyzed Oxygenation Mechanisms
Scripps Research Institute
2023-2025
Dana-Farber Cancer Institute
2023-2024
Broad Institute
2018-2022
Howard Hughes Medical Institute
2019-2021
Harvard University
2019-2021
University of Colorado Anschutz Medical Campus
2015-2017
University of Colorado Denver
2016-2017
Urbana University
2016
University of Illinois Urbana-Champaign
2015
Johns Hopkins Medicine
1995
Despite the availability of Cas9 variants with varied protospacer-adjacent motif (PAM) compatibilities, some genomic loci-especially those pyrimidine-rich PAM sequences-remain inaccessible by high-activity proteins. Moreover, broadening sequence compatibility through engineering can increase off-target activity. With directed evolution, we generated four that together enable targeting most sequences in human genome. Using phage-assisted noncontinuous evolution and eVOLVER-supported...
The simian immunodeficiency virus (SIV) macaque model of AIDS has provided a valuable system with which to investigate vaccine approaches for protection against human type 1 (HIV-1) infection. In particular, the ability macaques persistently infected attenuated infectious molecular clones SIV resist challenge pathogenic parental swarm conclusively demonstrated that protective immunity can be achieved by immunization prior exposure. breadth these responses and immunological correlates...
Abstract Human and simian immunodeficiency viruses (HIV SIV) exploit follicular lymphoid regions by establishing high levels of viral replication dysregulating humoral immunity. Follicular regulatory T cells (T FR ) are a recently characterized subset lymphocytes that influence the germinal centre response through interactions with helper FH ). Here, utilizing both human rhesus macaque models, we show impact HIV SIV infection on number function. We find proportionately numerically expand...
Abstract HIV-1 replication is concentrated within CD4+ T cells in B cell follicles of secondary lymphoid tissues during asymptomatic disease. Limited data suggest that a subset follicular helper (TFH) germinal centers (GC) highly permissive to HIV-1. Whether GC TFH are the major virus–producing vivo has not been established. In this study, we investigated permissivity ex by spinoculating and culturing tonsil with GFP reporter viruses. Using flow cytometry, higher percentages...
Base editing directly converts a target base pair into different in the genome of living cells without introducing double-stranded DNA breaks. While cytosine editors (CBE) and adenine (ABE) are used to install correct point mutations wide range organisms, extent distribution off-target edits mammalian embryos have not been studied detail. We analyze on-target proximal at 13 loci by variety CBEs ABE more than 430 alleles generated from mouse zygotic injections using newly published sequencing...
During chronic HIV infection, viral replication is concentrated in secondary lymphoid follicles. Cytotoxic CD8 T cells control extrafollicular regions, but not the follicle. Here, we show CXCR5hiCD44hiCD8 are a regulatory subset differing from conventional cells, and constitute majority of This subset, follicular (CD8 TFR), expand SIV exhibit enhanced expression Tim-3 IL-10, express less perforin compared to cells. TFR modestly limit helper (TFH), impair TFH IL-21 production via Tim-3,...
Follicular regulatory T (TFR) cells are a subset of CD4+ in secondary lymphoid follicles. TFR were previously included the follicular helper (TFH) cell subset, which consists that highly permissive to HIV-1. The permissivity HIV-1 is unknown. We find more than TFH R5-tropic ex vivo expressed CCR5 and CD4 supported higher frequencies viral fusion. Differences Ki67 expression correlated with replication. Inhibiting cellular proliferation reduced Lymph node from untreated HIV-infected...
Abstract A particular challenge in genome engineering has been the simultaneous introduction of mutations into linked (located on same chromosome) loci. Although CRISPR/Cas9 widely used to mutate individual sites, its application simultaneously targeting loci is limited as multiple nearby double-stranded DNA breaks created by Cas9 routinely result deletion sequences between cleavage sites. Base editing a newer form that directly converts C∙G-to-T∙A, or A∙T-to-G∙C, base pairs without...
Abstract A novel manganese C‐H amination catalyst is easily synthesized in one step from commercially available materials.