A5077785036- RNA Research and Splicing
- Acute Myeloid Leukemia Research
- Cancer Genomics and Diagnostics
- interferon and immune responses
- RNA modifications and cancer
- Advanced biosensing and bioanalysis techniques
- Immune Cell Function and Interaction
- Ubiquitin and proteasome pathways
- Immunodeficiency and Autoimmune Disorders
- DNA Repair Mechanisms
- Hemoglobinopathies and Related Disorders
- Chromatin Remodeling and Cancer
- RNA and protein synthesis mechanisms
- Plant Virus Research Studies
- Circular RNAs in diseases
- Virus-based gene therapy research
- Medical Imaging and Pathology Studies
- Hepatitis C virus research
- RNA Interference and Gene Delivery
- Radiopharmaceutical Chemistry and Applications
- Cytomegalovirus and herpesvirus research
- Chronic Lymphocytic Leukemia Research
- CRISPR and Genetic Engineering
- Single-cell and spatial transcriptomics
- Genomics and Chromatin Dynamics
Fred Hutch Cancer Center
2019-2023
University of Washington
2016-2023
Faculty of Public Health
2020
SF3B1 splicing factor mutations are near-universally found in myelodysplastic syndromes (MDS) with ring sideroblasts (RS), a clonal hematopoietic disorder characterized by abnormal erythroid cells iron-loaded mitochondria. Despite this remarkably strong genotype-to-phenotype correlation, the mechanism which mutant dysregulates iron metabolism to cause RS remains unclear due an absence of physiological models formation. Here, we report induced pluripotent stem cell model SF3B1-mutant MDS that...
Interferon (IFN) lambdas are critical antiviral effectors in hepatic and mucosal infections. Although IFNλ1, IFNλ2, IFNλ3 act antiviral, genetic association studies have shown that expression of the recently discovered IFNL4 is detrimental to hepatitis C virus (HCV) infection through a yet unknown mechanism. Intriguingly, human harbors variant introduces premature stop codon. We performed molecular biochemical characterization IFNλ4 determine its role regulation expression. found exhibits...
X-linked agammaglobulinemia (XLA) is an immune disorder caused by mutations in Bruton’s tyrosine kinase (BTK). BTK expressed B and myeloid cells, its deficiency results a lack of mature cells protective antibodies. We previously reported lentivirus (LV) replacement therapy that restored cell development function Btk Tec double knockout mice (a phenocopy human XLA). In this study, with the goal optimizing both level lineage specificity expression, we generated LV incorporating proximal...
LAGLIDADG homing endonucleases (LHEs) are compact with 20-22 bp recognition sites, and thus ideal scaffolds for engineering site-specific DNA cleavage enzymes genome editing applications. Here, we describe a general approach to LHE that combines rational design directed evolution, using yeast surface display high-throughput selection. This was employed alter the binding specificity of I-Anil recognize mutation in mouse Bruton tyrosine kinase (Btk) gene causative X-linked immunodeficiency...