A5053820618- HIV Research and Treatment
- HIV/AIDS drug development and treatment
- Immune Cell Function and Interaction
- Acute Myeloid Leukemia Research
- T-cell and B-cell Immunology
- Virus-based gene therapy research
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Monoclonal and Polyclonal Antibodies Research
- Immune Response and Inflammation
- CRISPR and Genetic Engineering
- Immunotherapy and Immune Responses
- Bacteriophages and microbial interactions
- Cancer therapeutics and mechanisms
- RNA Interference and Gene Delivery
- Retinoids in leukemia and cellular processes
- Cell Adhesion Molecules Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Genomics and Chromatin Dynamics
- Cytomegalovirus and herpesvirus research
- RNA and protein synthesis mechanisms
- Immune cells in cancer
- Herpesvirus Infections and Treatments
- Autophagy in Disease and Therapy
- CAR-T cell therapy research
University of Washington
2021-2025
Seattle Children's Hospital
2022-2024
Scripps Research Institute
2014-2023
California Institute for Regenerative Medicine
2022-2023
Scripps (United States)
2020
Scripps Institution of Oceanography
2020
La Jolla Institute For Molecular Medicine
2015
University of California, San Diego
1999-2007
University of Bern
2007
Beth Israel Deaconess Medical Center
2006
Efficient gene transfer into human hematopoietic stem cells (HSCs) is an important goal in the study of system as well for therapy disorders. A lentiviral vector based on immunodeficiency virus (HIV) was able to transduce CD34+ capable stable, long-term reconstitution nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. High-efficiency transduction occurred absence cytokine stimulation and resulted transgene expression multiple lineages up 22 weeks after transplantation.
CD4+ T cell clones were derived from mice immunized to keyhole limpet hemocyanin characterize the cytokine profiles of newly isolated clones. Surprisingly, several had an unrestricted profile, producing IL-2, IL-3, IL-4, IFN-gamma, and TNF after either Con A or Ag stimulation. The coproduction IL-2 IL-4 was confirmed at mRNA level. Subclones which contained RNA transcripts for, as well secreted, both thus confirming clonality original that expressed profile upon stimulation also other (hen...
We have analyzed the patterns of induced cytokine gene expression and cell cycle activity by CD4+ cells from mice, examined how these response change during aging process. were isolated spleens young adult old C57BL/6NNia mice stimulated in vitro with plate-bound anti-CD3 epsilon mAb. The then assessed over time for capacity to accumulate transcripts IL-1 alpha, beta, IL-2, IL-3, IL-4, IL-5, IL-6, IFN-gamma, TNF-alpha, TNF-beta; secrete IFN-gamma; progress through S phase. Before first major...
Abstract Previous studies indicate that the 3G11, CD45RB, and Pgp-1 determinants are differentially expressed on CD4+ T cell subsets in mouse. We used multicolor immunofluorescence staining flow cytofluorometric analysis to examine expression of each these splenic cells from young (age 3 6 mo) aged 24 26 C57BL/6 mice. The pool mice contained significantly reduced numbers 3G11+ CD45RBhi cells, but increased Pgp-1hi comparison with group. Analysis simultaneous all three subset revealed that,...
Treatment with HIV-1 protease inhibitors, a component of highly active antiretroviral therapy (HAART), often results in viral resistance. Structural and biochemical characterization 6X mutant arising from vitro selection compound 1, C2-symmetric diol inhibitor, has been previously described. We now show that 2, copper(I)-catalyzed 1,2,3-triazole derived shown to be potently effective against wild-type (IC50 = 6.0 nM), low nM activity 15.7 nM) the multidrug-resistant mutant. Compound 2...
The AutoDock family of software has been widely used in protein-ligand docking research. This study compares 4 and Vina the context virtual screening by using these programs to select compounds active against HIV protease.Both were rank members two chemical libraries, each containing experimentally verified binders protease. In case NCI Diversity Set II, both able significantly better than random (AUC = 0.69 0.68, respectively; p<0.001). binding energy predictions highly correlated this...
Human immunodeficiency virus (HIV) isolates differ in cell tropism, replication, pathogenicity, and syncytial induction vitro. CD4 + T cells were enumerated severe combined immunodeficient mice transplanted with human peripheral blood leukocytes (hu-PBL-SCID mice) infected HIV different vitro cytopathicity. Two noncytopathic, macrophage-tropic strains, HIV-1 SF162 HIV-2 UC1 , induced extensive depletion, whereas SF33 which is highly cytopathic for vitro, caused little depletion at equivalent...
Selective expression of the human class Ib HLA molecule HLA-G in immunologically protected sites and its function inhibition NK T-cell effector functions support an important role this immunoregulation. Here, we demonstrate that is constitutively expressed endocrine compartment pancreas. Surface determinant cells regulated response to growth inflammatory stimuli. Furthermore, provide evidence tissue may associate with a subset insulin-containing granules be shuttled cell surface secretory...
Abstract Here we present the Transcription Factor Encyclopedia (TFe), a new web-based compendium of mini review articles on transcription factors (TFs) that is founded principles open access and collaboration. Our consortium over 100 researchers has collectively contributed 130 pertinent human, mouse rat TFs. Notable features TFe website include high-quality PDF generator web API for programmatic data retrieval. aims to rapidly educate scientists about TFs they encounter through delivery...
The chemokine (C-C motif) receptor 5 (CCR5) serves as an HIV-1 co-receptor and is essential for cell infection with CCR5-tropic viruses. Loss of functional protects against HIV infection. Here, we report the successful targeting CCR5 in GFP-marked human induced pluripotent stem cells (iPSCs) using CRISPR/Cas9 single dual guide RNAs (gRNAs). Following CRISPER/Cas9-mediated gene editing a gRNA, 12.5% colonies demonstrated editing, which 22.2% showed biallelic determined by Surveyor nuclease...
Abstract Dendritic cells (DCs) are a heterogeneous population of that specialized for Ag processing and presentation. These believed to derive from both myeloid- lymphoid-committed precursors. Normal human PBMC-derived, CD14+ cell (monocyte)-derived, mouse hematopoietic progenitor-derived DCs were shown express the cell-restricted, ets family transcription factor PU.1. populations represent myeloid DCs. Hematopoietic progenitor PU.1 gene-disrupted (null) mice unable generate MHC class...
HIV-1-infected individuals can harbor viral isolates that use CCR5, as well CXCR4, for entry. To genetically engineer HIV-1 resistance in CD4(+) T cells, we assessed whether transient, adenovirus delivered zinc-finger nuclease (ZFN) disruption of genomic cxcr4 or stable lentiviral expression short hairpin RNAs (shRNAs) targeting CXCR4 mRNAs provides durable to challenge. ZFN-modification cells was found be superior cell integrated lentivirus-expressing shRNAs when were challenged with HIV-1s...
Significance Gene delivery by virus-like particles holds enormous therapeutic potential to correct inherited genetic disorders and prevent infectious disease. However, cells express antiviral factors that virus infection and, consequently, limit the success of gene therapy. Here, we reveal mechanism which drug rapamycin improves lentivirus-mediated delivery. Rapamycin treatment led degradation IFITM3, a broad potent protein inhibits entry into cells. IFITM3 is selectively cleared from...
Gene therapy currently in development for hemoglobinopathies utilizes ex vivo lentiviral transduction of CD34+ hematopoietic stem and progenitor cells (HSPCs). A small-molecule screen identified prostaglandin E2 (PGE2) as a positive mediator cells. Supplementation with PGE2 increased vector (LVV) approximately 2-fold compared to control methods no effect on cell viability. Transduction efficiency was consistently primary from multiple normal human donors patients β-thalassemia or sickle...