A5036418672- CAR-T cell therapy research
- CRISPR and Genetic Engineering
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Chronic Lymphocytic Leukemia Research
- Macrophage Migration Inhibitory Factor
- Nuclear Receptors and Signaling
- Cytokine Signaling Pathways and Interactions
- Viral Infectious Diseases and Gene Expression in Insects
- RNA Interference and Gene Delivery
- Immunotherapy and Immune Responses
- Advanced biosensing and bioanalysis techniques
- Peptidase Inhibition and Analysis
- Chronic Myeloid Leukemia Treatments
- Lymphoma Diagnosis and Treatment
- Cytomegalovirus and herpesvirus research
- Nanowire Synthesis and Applications
- Glycosylation and Glycoproteins Research
- Monoclonal and Polyclonal Antibodies Research
- Virus-based gene therapy research
- Mast cells and histamine
- Asthma and respiratory diseases
Gladstone Institutes
2021-2025
University of California, San Francisco
2019-2025
Howard Hughes Medical Institute
2024
University of California, Berkeley
2023
UCSF Helen Diller Family Comprehensive Cancer Center
2022
Parker Institute for Cancer Immunotherapy
2022
Abstract DNA nanostructures are a promising tool to deliver molecular payloads cells. origami structures, where long single-stranded is folded into compact nanostructure, present an attractive approach package genes; however, effective delivery of genetic material cell nuclei has remained critical challenge. Here, we describe the use encoding intact human gene and fluorescent protein as templates for integration by CRISPR-mediated homology-directed repair (HDR). Our design includes...
Chimeric antigen receptors (CARs) repurpose natural signaling components to retarget T cells refractory cancers but have shown limited efficacy in persistent, recurrent malignancies. Here, we introduce “CAR Pooling,” a multiplexed approach rapidly identify CAR designs with clinical potential. Forty CARs domains derived from range of immune cell lineages were evaluated pooled assays for their ability stimulate critical effector functions during repetitive stimulation that mimics long-term...
Peyer’s patches (PPs) are lymphoid structures situated adjacent to the intestinal epithelium that support B cell responses give rise many IgA-secreting cells. Induction of isotype switching IgA in PPs requires interactions between cells and TGFβ-activating conventional dendritic type 2 (cDC2s) subepithelial dome (SED). However, mechanisms promoting cDC2 positioning SED unclear. Here, we found PP cDC2s express GPR35, a receptor promotes migration response various metabolites, including...
Abstract Engineering T cell specificity and function at multiple loci can generate more effective cellular therapies, but current manufacturing methods produce heterogenous mixtures of partially engineered cells. Here we develop a one-step process to enrich unlabeled cells containing knock-ins target using family repair templates named synthetic exon expression disruptors (SEEDs). SEEDs associate transgene integration with the disruption paired endogenous surface protein while preserving in...
It has long been appreciated that highly autoreactive BCRs are actively removed from the developing B cell repertoire by Ag-dependent receptor editing and deletion. However, there is persistent debate about whether mild autoreactivity simply tolerated or positively selected into mature as well at what stage, to extent, under conditions, which compartments this occurs. In study, we describe two minor, trackable populations of cells in B1-8i Ig transgenic mice express VH186.2 H chain recognize...
B cell clones compete for entry into and dominance within germinal centers (GCs), where the highest-affinity receptors (BCRs) are selected. However, diverse low-affinity cells can enter reside in GCs extended periods. To reconcile these observations, we hypothesize that a negative feedback loop may operate to preferentially restrain high-affinity from monopolizing early GC niche. Here, report role nuclear receptor NUR77/Nr4a1 this process. We show NUR77 expression scales with antigen...
Abstract CRISPR-Cas9 offers unprecedented opportunities to modify genome sequences in primary human cells study disease variants and reprogram cell functions for next-generation cellular therapies. CRISPR has several potential advantages over widely used retroviral vectors including: 1) site-specific transgene insertion via homology directed repair (HDR), 2) reductions the cost complexity of modification. Despite rapid progress with ex vivo engineering, many novel research clinical...
Abstract Multiplexed reprogramming of T cell specificity and function can generate powerful next-generation cellular therapies. However, current manufacturing methods produce heterogenous mixtures partially engineered cells. Here, we develop a one-step process to enrich for unlabeled cells with knock-ins at multiple target loci using family repair templates named S ynthetic E xon/ xpression Disruptors (SEEDs). SEED engineering associates transgene integration the disruption paired endogenous...
Abstract Although it has long been appreciated that multivalent antigens – and particularly viral epitope display produce extremely rapid, robust, T-independent humoral immune responses, the biochemical basis for such potency incompletely understood. Here we take advantage of a set neutral liposomes size are engineered to affinity mutants model antigen (Ag) hen egg lysozyme at precisely varied density. We show particulate Ag by induces highly potent B cell responses dose-and...
Initiation of B-cell receptor (BCR) 1 signaling, and subsequent antigen-encounter in germinal centers 2,3 represent milestones B-lymphocyte development that are both marked by sharp increases CD25 surface-expression. Oncogenic signaling leukemia (B-ALL) 4 lymphoma 5 also induced CD25-surface expression. While is known as an IL2-receptor chain on T- NK-cells 6-9 , the significance its expression B-cells was unclear. Our experiments based genetic mouse models engineered patient-derived...
ABSTRACT Ag stimulation (signal 1) triggers B cell activation and proliferation, primes cells to recruit, engage, respond T help 2). However, failure receive signal 2 within a defined window of time results in an abortive round followed by anergy or apoptosis. Although the molecular basis has been extensively dissected, mechanisms that restrain Ag-stimulated cells, enforce dependence upon co-stimulation, are incompletely understood. Nr4a1-3 encode small family orphan nuclear receptors...
Abstract DNA nanostructures are a promising tool for delivery of variety molecular payloads to cells. origami structures, where 1000’s bases folded into compact nanostructure, present an attractive approach package genes; however, effective genetic material cell nuclei has remained critical challenge. Here we describe the use encoding intact human gene and fluorescent-protein as templates integration by CRISPR-mediated homology-directed repair (HDR). Our design includes CRISPR-Cas9...
Abstract Successful initiation of the B-cell receptor (BCR) signaling, and subsequent antigen-encounter in germinal centers are both marked by sharp increases CD25 surface-expression. Likewise, oncogenic signaling leukemia (B-ALL) lymphoma induces CD25-surface expression. While is known as an IL2-receptor chain on T- NK-cells, significance its expression B-cells was unclear. We discovered that, rather than functioning chain, expressed feedback regulates BCR-signaling or mimics....