A5014889008- interferon and immune responses
- CAR-T cell therapy research
- Parasitic infections in humans and animals
- CRISPR and Genetic Engineering
- Influenza Virus Research Studies
- Virus-based gene therapy research
- Prenatal Screening and Diagnostics
- Parasitic Infections and Diagnostics
- Research on Leishmaniasis Studies
- Viral Infections and Vectors
- Toxoplasma gondii Research Studies
- Hemoglobinopathies and Related Disorders
- Pancreatic function and diabetes
- Immunotherapy and Immune Responses
- Advancements in Semiconductor Devices and Circuit Design
- Mosquito-borne diseases and control
- Nanowire Synthesis and Applications
- Cytokine Signaling Pathways and Interactions
- Trypanosoma species research and implications
- Epigenetics and DNA Methylation
- Molecular Sensors and Ion Detection
- Immune cells in cancer
- Neuroblastoma Research and Treatments
- Parasite Biology and Host Interactions
- Cancer Immunotherapy and Biomarkers
University of Washington
2013-2024
Seattle Children's Hospital
2017-2024
Infectious Disease Research Institute
2010-2015
Centers for Disease Control and Prevention
2003-2009
National Center for Emerging and Zoonotic Infectious Diseases
2009
Georgia State University
2001
Visceral leishmaniasis (VL) is diagnosed by microscopic confirmation of the parasite in bone marrow, spleen or lymph node aspirates. These procedures are unsuitable for rapid diagnosis VL field settings. The development rK39-based diagnostic tests (RDT) revolutionized offering high sensitivity and specificity detecting disease Indian subcontinent; however, these have been less reliable African subcontinent (sensitivity range 75-85%, 70-92%). We addressed limitations rK39 with a new synthetic...
CRISPR-Cas9–edited hematopoietic stem cells produce long-term engraftment and fetal hemoglobin reactivation in nonhuman primates.
Gene editing following designer nuclease cleavage in the presence of a DNA donor template can revert mutations disease-causing genes. For optimal benefit, reversion point mutation HBB leading to sickle cell disease (SCD) would permit precise homology-directed repair (HDR) while concurrently limiting on-target non-homologous end joining (NHEJ)-based disruption. In this study, we directly compared relative efficiency co-delivery novel CRISPR/Cas9 ribonucleoprotein targeting association with...
Abstract Diffuse intrinsic pontine glioma (DIPG) is a fatal central nervous system (CNS) tumor that confers median survival of 11 months. As B7-H3 expressed on pediatric CNS tumors, we conducted BrainChild-03, single-center, dose-escalation phase 1 clinical trial repetitive intracerebroventricular (ICV) dosing B7-H3-targeting chimeric antigen receptor T cells (B7-H3 CAR cells) for children with recurrent or refractory tumors and DIPG. Here report results from Arm C, restricted to patients...
Abstract Therapy of intracellular pathogens can be complicated by drug toxicity, resistance, and the need for prolonged treatment regimens. One approach that has shown promise is immunotherapy. Leishmaniasis, a vector-borne disease ranked among six most important tropical infectious diseases World Health Organization, been treated clinically with crude or defined vaccine preparations cytokines, such as IFN-γ GM-CSF, in combination chemotherapy. We have attempted to develop an improved...
ABSTRACT The cellular response to virus infection is initiated when pathogen recognition receptors (PRR) engage viral pathogen-associated molecular patterns (PAMPs). This process results in induction of downstream signaling pathways that activate the transcription factor interferon regulatory 3 (IRF3). IRF3 plays a critical role antiviral immunity drive expression innate immune genes, including those encoding factors, type 1 interferon, and modulatory cytokines, act concert restrict...
RNA helicases play an important role in the response to microbial infection. Retinoic acid inducible gene-I (RIG-I) and members of RIG-I-like receptor (RLR) family function as cytoplasmic pattern recognition receptors (PRRs) whose actions are essential for viruses. RIG-I association with pathogen-associated molecular patterns (PAMPs) within viral leads its activation signaling via mitochondrial antiviral (MAVS) adapter protein. This interaction mediates downstream events that drive innate...
PURPOSE B7-H3 is an immunoregulatory protein overexpressed by many pediatric solid tumors with limited expression on critical organs, making it attractive immunotherapy target. We present a first-in-human phase I clinical trial systemically administered chimeric antigen receptor (CAR) T cells for young patients relapsed or refractory tumors. PATIENTS AND METHODS Patients were enrolled onto to examine the safety of B7-H3–specific CARs at various dose levels (DLs) using standard 3 + escalation...
ABSTRACT The Western blot for cysticercosis, which uses lentil lectin purified glycoprotein (LLGP) antigens extracted from the metacestode of Taenia solium , has been “gold standard” serodiagnostic assay since it was first described in 1989. We report that diagnostic at 14, 18, and 21 kDa, as well some larger disulfide-bonded antigens, are actually all members a very closely related family proteins, 8-kDa antigens. genes 18 unique, mature proteins have identified. Nine these were chemically...
Visceral leishmaniasis (VL) can be fatal without timely diagnosis and treatment. Treatment efficacies vary due to drug resistance, toxicity co-morbidities. It is important monitor treatment responsiveness confirm cure curtail relapse. Currently, microscopy of spleen, bone marrow or lymph node biopsies the only definitive method evaluate cure. A less invasive test for success a high priority VL management.In this study, we describe development capture ELISA based on detecting Leishmania...
Elements within the γ-hemoglobin promoters (HBG1 and HBG2) function to bind transcription complexes that mediate repression of fetal hemoglobin expression. Sickle cell disease (SCD) subjects with a 13-bp deletion in HBG1 promoter exhibit clinically favorable hereditary persistence (HPFH) phenotype. We developed TALENs targeting homologous HBG de-repress hemoglobin. Transfection human CD34+ cells TALEN mRNA resulted indel generation (43%) HBG2 (74%) including HPFH (∼6%). Erythroid...
Abstract Background Relapsed/refractory pediatric CNS tumors have a poor prognosis. EGFR is commonly overexpressed, but EGFRvIII mutations are uncommon. To target these tumors, we used chimeric antigen receptor (CAR) T cells with binder based on mAb806 which recognizes ectopically expressed wild-type and EGFRvIII. Methods In this open-label phase 1 clinical trial, patients age 1-26 years EGFR+ received weekly infusions of 1-2.5 x 107 CAR into the tumor resection bed or lateral ventricle via...
Diagnosis of Taenia solium cysticercosis is an important component in the control and elimination taeniasis. New detection assays using recombinant synthetic antigens originating from lentil lectin-purified glycoproteins (LLGPs) T. cysticerci were developed a QuickELISA™ format. We analyzed panel 474 serum samples composed 108 donors with two or more viable cysts, 252 persons other parasitic infections, 114 no documented illnesses. The sensitivities specificities T24H QuickELISA™, GP50...
Abstract BACKGROUND BrainChild-04 is a first-in-human clinical trial of quad-chimeric antigen receptor (CAR) T cell therapy for children and young adults with central nervous system (CNS) tumors. This administers repeated locoregional CAR cells targeting B7-H3, EGFR, HER2, IL-13Ralpha2 (“quad-CAR cells”), leveraging multi-antigen to address the tumor heterogeneity high-grade CNS METHODS The primary endpoints are feasibility safety, secondary disease response correlative studies activity....
Abstract BACKGROUND BrainChild-03 is a first-in-human clinical trial that completed the phase 1 component of repeatedly dosed intraventricular B7-H3 CAR T cells to children with diffuse intrinsic pontine glioma (DIPG) without lymphodepleting chemotherapy. METHODS We report on Arm C, patients DIPG receiving up 10x10^7 B7-H3CAR cells/dose. Primary endpoints were feasibility and safety. Secondary disease response correlatives activity. RESULTS 23 enrolled. All had successful manufacturing. 21...
The recognition of pathogen associated molecular patterns (PAMPs) by pattern receptors (PRR) during viral infection initiates the induction antiviral signaling pathways, including activation Interferon Regulator Factor 3 (IRF3). We identified small molecule compounds that activate IRF3 through MAVS, thereby inhibiting viruses families Flaviviridae (West Nile virus, dengue virus and hepatitis C virus), Filoviridae (Ebola Orthomyxoviridae (influenza A Arenaviridae (Lassa virus) Paramyxoviridae...
We evaluated three diagnostic antigens (recombinant GP50, recombinant T24H, and synthetic Ts18var1) for cysticercosis found that all performed well in detecting humans pigs several assay formats. These were adapted to a new antibody detection format (QuickELISA). With one single incubation step which involves reactants except the enzyme substrate, QuickELISA is particularly suited automation. formatted Triturus EIA analyzer testing large numbers of samples. formats rGP50 rT24H have better...
Abstract Retinoic acid inducible gene I (RIG-I) is essential for directing and priming the host immune response against many RNA viruses. A diverse small molecule library was used in a cell-based screening approach to identify drug-like compounds that could target RIG-I signaling pathway induce downstream IRF3 drive innate antiviral immunity. We identified activate discrete subsets of genes. class hydroxyquinoline activation immunity cultured cells decrease viral load infectious virus...
e14626 Background: B7-H3 expression by a broad range of pediatric solid tumors has led to development B7-H3-directed chimeric antigen receptor (B7-H3-CAR) T cells. However, early phase clinical trials B7-H3-CAR cells in recurrent/refractory demonstrated inconsistent CAR cell expansion and limited anti-tumor activity. We subsequently developed dual transduced product expressing CD19-CAR (CARB7H3x19) enhance with antigenic stimulation normal B (STRIvE-02 Arm B). Augmented was observed but...
<h3>Background</h3> Patients with relapsed/refractory osteosarcoma (OS) have dismal outcomes, and there are no systemic therapies that provide a survival benefit. Chimeric antigen receptor (CAR) T-cell immunotherapy involves the adoptive transfer of T-lymphocytes been engineered to recognize tumor-specific antigens, resulting in targeted lysis malignant cells. Folate (FR)-α is highly expressed OS FRβ found on tumor-associated macrophages but limited normal tissues, making FR an ideal target...
Abstract BACKGROUND BrainChild-04 is a first-in-human clinical trial of quad-chimeric antigen receptor (CAR) T cell therapy for children and young adults with central nervous system (CNS) tumors. This administers repeated locoregional CAR cells targeting B7-H3, EGFR, HER2, IL-13Ralpha2 (“quad-CAR cells”), leveraging multi-antigen to address the tumor heterogeneity high-grade CNS METHODS The primary endpoints are feasibility safety, secondary disease response correlative studies activity....