Warren D. Reynolds
A5059036898- CAR-T cell therapy research
- Single-cell and spatial transcriptomics
- Viral Infectious Diseases and Gene Expression in Insects
- Glioma Diagnosis and Treatment
- Acute Lymphoblastic Leukemia research
- Cancer Genomics and Diagnostics
- Genomics and Chromatin Dynamics
- Virus-based gene therapy research
- Immunotherapy and Immune Responses
- RNA modifications and cancer
- Immune Cell Function and Interaction
- Analytical Chemistry and Chromatography
- Nanowire Synthesis and Applications
- Cardiac electrophysiology and arrhythmias
- Mass Spectrometry Techniques and Applications
- Electron Spin Resonance Studies
- Integrated Circuits and Semiconductor Failure Analysis
- Advancements in Semiconductor Devices and Circuit Design
- Analytical Chemistry and Sensors
- Acute Myeloid Leukemia Research
- Electrochemical Analysis and Applications
- Silicon Carbide Semiconductor Technologies
- Photonic and Optical Devices
- Microfluidic and Capillary Electrophoresis Applications
- Ion channel regulation and function
Stanford University
2020-2024
Stratford University
2023
Palo Alto University
2023
Dynamic Systems (United States)
2021
Miami University
2019-2020
University of Arizona
1989
National Center for Toxicological Research
1975-1976
Abstract Diffuse intrinsic pontine glioma (DIPG) and other H3K27M-mutated diffuse midline gliomas (DMGs) are universally lethal paediatric tumours of the central nervous system 1 . We have previously shown that disialoganglioside GD2 is highly expressed on cells demonstrated promising preclinical efficacy GD2-directed chimeric antigen receptor (CAR) T 2 , providing rationale for a first-in-human phase I clinical trial (NCT04196413). Because CAR cell-induced brainstem inflammation can result...
Abstract Despite impressive progress, more than 50% of patients treated with CD19-targeting chimeric antigen receptor T cells (CAR19) experience progressive disease. Ten 16 large B cell lymphoma (LBCL) disease after CAR19 treatment had absent or low CD19. Lower surface CD19 density pretreatment was associated To prevent relapse − lo disease, we tested a bispecific CAR targeting and/or CD22 (CD19-22.BB.z-CAR) in phase I clinical trial ( NCT03233854 ) adults relapsed/refractory acute...
H3K27M-mutant diffuse midline gliomas (DMGs) express high levels of the disialoganglioside GD2 (ref. 1). Chimeric antigen receptor-modified T cells targeting (GD2-CART) eradicated DMGs in preclinical models2. Arm A Phase I trial no. NCT04196413 3) administered one intravenous (IV) dose autologous GD2-CART to patients with pontine (DIPG) or spinal DMG (sDMG) at two (DL1, 1 × 106 kg−1; DL2, 3 kg−1) following lymphodepleting chemotherapy. Patients clinical imaging benefit were eligible for...
BackgroundOutcomes are poor for patients with large B-cell lymphoma who relapse after CD19-directed chimeric antigen receptor (CAR) T-cell therapy (CAR19). CD22 is a nearly universally expressed surface and the efficacy of CD22-directed CAR (CAR22) in unknown, which was what we aimed to examine this study.MethodsIn single centre, open-label, dose-escalation phase 1 trial, intravenously administered CAR22 at two dose levels (1 million 3 CAR22-positive T cells per kg bodyweight) adult (aged...
Abstract Although alterations in chromatin structure are known to exist tumors, how these relate molecular phenotypes cancer remains be demonstrated. Multi-omics profiling of human tumors can provide insight into propagated through the pathway gene expression result malignant protein expression. We applied multi-omics accessibility, RNA abundance, and abundance 36 thyroid primary metastases, patient-match normal tissue. Through quantification accessibility associated with active...
H3K27M-mutant diffuse midline gliomas (DMGs) express high levels of the GD2 disialoganglioside and chimeric antigen receptor modified T-cells targeting (GD2-CART) eradicate DMGs in preclinical models. Arm A Phase I trial NCT04196413 administered one IV dose autologous GD2-CART to patients with pontine (DIPG) or spinal (sDMG) glioma at two (DL1=1e6/kg; DL2=3e6/kg) following lymphodepleting (LD) chemotherapy. Patients clinical imaging benefit were eligible for subsequent...
Master transcription factors (TFs) directly regulate present and future cell states by binding DNA regulatory elements driving gene-expression programs. Their abundance influences epigenetic priming to different fates at the chromatin level, especially in context of differentiation. In order link TF protein changes motif accessibility open chromatin, we developed InTAC-seq, a method for simultaneous quantification genome-wide intracellular fixed cells. Our produces high-quality data is...
Membrane proteins are responsible for conducting essential biological functions that necessary the survival of living organisms. In spite their physiological importance, limited structural information is currently available as a result challenges in applying biophysical techniques studying these protein systems. Electron paramagnetic resonance (EPR) spectroscopy very powerful technique to study and dynamic properties membrane proteins. However, application EPR native membrane-bound state...
KCNQ1 (Kv7.1 or KvLQT1) is a potassium ion channel protein found in the heart, ear, and other tissues. In complex with KCNE1 accessory protein, it plays role during repolarization phase of cardiac action potential. Mutations have been associated several diseases, including congenital deafness long QT syndrome. Nuclear magnetic resonance (NMR) structural studies detergent micelles cryo-electron microscopy structure from Xenopus laevis shown that voltage sensor domain (Q1-VSD) has four...
Abstract Background: H3K27M-mutated DMGs are universally lethal central nervous system tumors that express high levels of the disialoganglioside GD2. IV administered GD2-CAR T cells (GD2-CART) regress DMG in preclinical models, and locoregionally delivered CARs demonstrate enhanced activity xenograft models brain tumors. Methods: NCT04196413 is a 3+3 Phase I dose escalation trial testing GD2-CART patients with H3K27M DMG, dose-limiting toxicities (DLT) considered independently for DIPG...
Chemotherapy-associated cardiotoxicity is a common adverse event. Immune checkpoint inhibitors (ICI) – new class of monoclonal antibodies have revolutionized the management various diseases. Their use expected to increase in near future and their cardiac side effects been increasingly recognized.We describe case 67-year-old female patient with urothelial carcinoma undergoing treatment pembrolizumab who presented emergency department progressive fatigue, retrosternal pain palpitations for...
Background: Patients with relapsed/refractory large B-cell lymphoma (LBCL) who progress after CD19 CAR T-cell therapy (CAR19) have poor outcomes. CD22 is expressed on the majority of lymphomas. Here, we report evaluation an autologous targeting (CAR22) for treatment adult patients R/R LBCL predominantly relapsed CAR19. Aims: The primary aims this trial assessed ability to successfully manufacture CAR22 and determine initial safety CAR22. Key secondary included overall response rate, complete...
Hematopoietic stem and progenitor cell (HSPC) transplantation is an essential therapy for hematological conditions, but finer definitions of human HSPC subsets with associated function could enable better tuning grafts more routine, lower-risk application. To deeply phenotype HSPCs, following a screen 328 antigens, we quantified 41 surface proteins functional regulators on millions CD34+ CD34- cells, spanning four primary hematopoietic tissues: bone marrow, mobilized peripheral blood, cord...
Abstract Background: Chimeric antigen receptor T cells (CARTs) hold promising therapeutic potential for refractory tumors. GD2 is a tumor expressed on neuroblastoma and osteosarcoma. In initial studies, expressing 1st generation GD2-CARTs were shown to be safe mediated modest antitumor activity in some patients with neuroblastoma. Methods: We developed 3rd GD2-CART (GD2-CAR.OX40.28.z.ICD9) conducted phase I trial (NCT02107963) determine the feasibility of producing safety administering...