A5083225904- Immune Cell Function and Interaction
- Virus-based gene therapy research
- T-cell and B-cell Immunology
- RNA Interference and Gene Delivery
- Immunotherapy and Immune Responses
- Immune Response and Inflammation
- Diabetes and associated disorders
- Pancreatic function and diabetes
- Cytokine Signaling Pathways and Interactions
- Microtubule and mitosis dynamics
- Neonatal Respiratory Health Research
- Immunodeficiency and Autoimmune Disorders
- Cell Adhesion Molecules Research
- Glioma Diagnosis and Treatment
- Blood disorders and treatments
- Radiation Therapy and Dosimetry
- Veterinary Oncology Research
- Genetics, Aging, and Longevity in Model Organisms
- CRISPR and Genetic Engineering
- Epigenetics and DNA Methylation
- Angiogenesis and VEGF in Cancer
- Neuroendocrine Tumor Research Advances
- Chemical Reactions and Isotopes
- Animal Genetics and Reproduction
- Multiple Sclerosis Research Studies
University of Washington
2014-2025
Seattle University
1990-2017
Northwest University
2015
University of Washington Applied Physics Laboratory
2008
Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa
2004
Northwestern University
2002
University of California, San Francisco
1988-2002
Fred Hutch Cancer Center
1999
Bristol-Myers Squibb (United States)
1994
Cancer Research Institute
1988-1993
Direct gene transfer into adult animals resulting in generalized or tissue-specific expression would facilitate rapid analysis of transgene effects and allow precise vivo manipulation biologic processes at the molecular level. A single intravenous injection plasmid:cationic liposome complexes mice efficiently transfected virtually all tissues. In addition to vascular endothelial cells, most extravascular parenchymal cells present many tissues including lung, spleen, lymph nodes, bone marrow...
Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) characterized by plaques infiltrating CD4+ and CD8+ T cells. Studies MS experimental autoimmune encephalomyelitis (EAE), an animal model MS, focus on contribution myelin-specific The role cells in mediating EAE or has not been described previously. Here, we demonstrate that induce severe CNS autoimmunity mice. pathology clinical symptoms cell–mediated similarities to seen EAE. These data suggest could...
The low-affinity receptor for leukemia inhibitory factor (LIFR) interacts with gp130 to induce an intracellular signal cascade. LIFR-gp130 heterodimer is implicated in the function of diverse systems. Normal placentation disrupted LIFR mutant animals, which leads poor intrauterine nutrition but allows fetuses continue term. Fetal bone volume reduced greater than three-fold and number osteoclasts increased six-fold, resulting severe osteopenia perinatal bone. Astrocyte numbers are spinal cord...
Individuals with X-linked hyper-IgM syndrome fail to express functional CD40 ligand (CD40L) and, as a consequence, are incapable of mounting protective antibody responses opportunistic bacterial infections. To address the role CD40L in humoral immunity, we created, through homologous recombination, mice deficient expression. These exhibited no gross developmental deficiencies or health abnormalities and contained normal percentages B T cell subpopulations. CD40L-deficient did display...
Purified CD4+ lymph node T cells were sorted into two populations on the basis of their expression CD45RB (CD45RBhi and CD45RBlo) injected congenic severe combined immunodeficient (SCID) mice. After a period time that was dependent number injected, SCID mice received CD45RBhi/CD4+ developed wasting disease not seen in CD4+/CD45RBlo or whole cells. At death, CD4+/CD45RBhi had increased spleen cellularity compared with normal The contained neither CD8+ nor surface immunoglobulin M-positive...
Epigenetic therapy may induce tumor-suppressive Notch signaling in patients with small cell lung cancer.
The ability to express transgenes selectively within the lung will greatly facilitate development of gene therapy for a variety human diseases. We have demonstrated that aerosol administration chloramphenicol acetyltransferase (CAT) expression plasmid complexed cationic liposomes produces high-level, lung-specific CAT in mice vivo. Significant levels activity are seen lungs at least 21 days following aerosolization. In situ immunostaining intracellular protein reveals majority airway...
Despite the widespread use of vaccinia virus (VV) as a vector for other Ags and smallpox vaccine, there is little information available about protective components immune response following VV infection. In this study, protection against wild-type was evaluated in mice with respect to relative contributions CD8(+) T cells vs that CD4(+) Ab. C57BL/6 primed Western Reserve strain mount significant IgM IgG Ab responses, specific cytotoxic cell IFN-gamma responses cells, effectively clear virus....
Epigenetic alterations, particularly in DNA methylation, are ubiquitous cancer, yet the molecular origins and consequences of these alterations poorly understood. CTCF, a DNA-binding protein that regulates higher-order chromatin organization, is frequently altered by hemizygous deletion or mutation human cancer. To date, causal role for CTCF cancer has not been established. Here, we show Ctcf knockout mice markedly susceptible to spontaneous, radiation-, chemically induced broad range...
Multiple autoimmune diseases, including type 1 diabetes, rheumatoid arthritis, Graves disease, and systemic lupus erythematosus, are associated with an allelic variant of protein tyrosine phosphatase nonreceptor 22 (PTPN22), which encodes the LYP. To model human disease-linked LYP-R620W, we generated knockin mice expressing analogous mutation, R619W, in murine ortholog PEST domain (PEP). In contrast a previous report, found that this exhibits normal stability, but significantly alters...
Patients with the immunodeficiency Wiskott-Aldrich syndrome (WAS) frequently develop systemic autoimmunity. Here, we demonstrate that mutation of WAS gene results in B cells are hyperresponsive to cell receptor and Toll-like (TLR) signals vitro, thereby promoting a cell–intrinsic break tolerance. Whereas this defect leads autoantibody production protein–deficient (WASp−/−) mice without overt disease, chimeric which only lineage lacks WASp exhibit severe autoimmunity characterized by...
Systemic lupus erythematosus is a multisystem autoimmune disease characterized by autoantibodies targeting nucleic acid-associated Ags. The endosomal TLRs TLR7 and TLR9 are critical for generation of Abs RNA- or DNA-associated Ags, respectively. In murine models, deletion limits inflammation, whereas exacerbates disease. Whether B cell myeloid TLR7/TLR9 signaling responsible these effects has not been fully addressed. this study, we use chimeric strategy to evaluate the effect cell-intrinsic...
The first study of Magnetic Particle Imaging (MPI) for tomographic imaging cancer targeted iron oxide nanoparticles.
Abstract Multiple sclerosis (MS) is an inflammatory disease of the CNS that causes demyelination nerve cells and destroys oligodendrocytes, neurons, axons. Historically, MS has been thought to be a CD4 T cell–mediated autoimmune white matter. However, recent studies identified CD8 cell infiltrates gray matter lesions in patients. These findings suggest Ags other than myelin proteins may involved during process. In this article, we show reactive glial fibrillary acidic protein (GFAP),...