A5081098773- Virus-based gene therapy research
- CAR-T cell therapy research
- Single-cell and spatial transcriptomics
- Hematopoietic Stem Cell Transplantation
- CRISPR and Genetic Engineering
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Cancer Genomics and Diagnostics
- Immunodeficiency and Autoimmune Disorders
- Cytomegalovirus and herpesvirus research
- Nanowire Synthesis and Applications
- Viral Infections and Immunology Research
- Bacteriophages and microbial interactions
- Bacterial Genetics and Biotechnology
- Hemoglobinopathies and Related Disorders
- Mesenchymal stem cell research
- RNA Interference and Gene Delivery
- Prenatal Screening and Diagnostics
- Chromosomal and Genetic Variations
- Parvovirus B19 Infection Studies
- Biosimilars and Bioanalytical Methods
- Viral gastroenteritis research and epidemiology
- Cell Image Analysis Techniques
- Bacillus and Francisella bacterial research
Fred Hutch Cancer Center
2017-2023
Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa
2019-2023
University of Washington
2012-2020
Cancer Research Center
2019
Abstract Chimeric antigen receptor (CAR) T-cell therapy has produced remarkable anti-tumor responses in patients with B-cell malignancies. However, clonal kinetics and transcriptional programs that regulate the fate of CAR-T cells after infusion remain poorly understood. Here we perform TCRB sequencing, integration site analysis, single-cell RNA sequencing (scRNA-seq) to profile CD8 + from products (IPs) blood undergoing CD19 immunotherapy. shows diversity is highest IPs declines following...
A population of hematopoietic stem cells with superior engraftment and repopulating abilities has been identified in nonhuman primates.
Hematopoietic stem cell (HSC) gene therapy has the potential to cure many genetic, malignant, and infectious diseases. We have shown in a nonhuman primate transplantation model that CD34+CD90+ fraction was exclusively responsible for multilineage engraftment hematopoietic reconstitution. In this study, we show translational of HSC-enriched CD34 subset lentivirus-mediated therapy. Alternative HSC enrichment strategies include purification CD133+ cells or CD38low/- subsets CD34+ from human...
In vivo tracking of retrovirus-tagged blood stem and progenitor cells is used to study hematopoiesis. Two techniques are most frequently: sequencing the locus retrovirus insertion, termed integration site analysis, or DNA barcode sequencing. Of these, analysis currently only available technique for monitoring clonal pools in patients treated with retrovirus-modified cells. A key question how these two compare their ability detect quantify contributions. this study, we assessed both methods...
To help define the biological functions of nonessential genes Francisella novicida, we measured growth arrayed members a comprehensive transposon mutant library under variety nutrition and stress conditions. Mutant phenotypes were identified for 37% genes, corresponding to ten carbon source utilization pathways, nine amino acid- nucleotide-biosynthetic intrinsic antibiotic resistance traits, six other traits. The greatest surprise analysis was large number genotype-phenotype relationships...
Hematopoietic stem and progenitor cell (HSPC)-based ex vivo gene therapy has demonstrated clinical success for X-linked severe combined immunodeficiency (SCID-X1) patients who lack a suitable donor HSPC transplantation. Nevertheless, this form of treatment is associated with an increased risk infectious disease complications genotoxicity mainly due to the conditioning regimen. In addition, approaches require sophisticated facilities manufacture gene-modified cells care after chemotherapy....
Over the past decade, numerous gene-editing platforms which alter host DNA in a highly specific and targeted fashion have been described. Two notable examples are zinc finger nucleases (ZFNs), first platform to be tested clinical trials, more recently, CRISPR/Cas9. Although CRISPR/Cas9 approaches become arguably most popular field, therapeutic advantages disadvantages of each strategy only beginning emerge. We established nonhuman primate (NHP) model that serves as strong predictor...
ABSTRACT Hematopoietic stem cell (HSC) gene therapy has the potential to cure many genetic, malignant and infectious diseases. We have shown in a nonhuman primate (NHP) HSC transplantation model that CD34 + CD90 fraction was exclusively responsible for multilineage engraftment hematopoietic reconstitution. Here we show translational of this HSC-enriched subset lentivirus-mediated therapy. Alternative HSC-enrichment strategies include purification CD133 cells or CD38 low/- subsets from human...
ABSTRACT Reconstitution after hematopoietic stem cell (HSC) transplantation is assumed to occur in two distinct phases: initial recovery mediated by short-term progenitors and long-term repopulation multipotent HSCs which do not contribute reconstitution during the first 6-9 months. We have previously reported exclusive engraftment of HSC-enriched CD34 + CD45RA - CD90 phenotype a nonhuman primate model. Here, we closely followed clonal diversity kinetics these animals. Enhanced sampling high...