A5072015517- CAR-T cell therapy research
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Silicon Carbide Semiconductor Technologies
- Cytomegalovirus and herpesvirus research
- RNA Interference and Gene Delivery
- Herpesvirus Infections and Treatments
- T-cell and B-cell Immunology
- Advancements in Semiconductor Devices and Circuit Design
- Mesenchymal stem cell research
- Virus-based gene therapy research
- Toxin Mechanisms and Immunotoxins
- Extracellular vesicles in disease
- Mosquito-borne diseases and control
- COVID-19 Impact on Reproduction
- Glioma Diagnosis and Treatment
- Cancer-related molecular mechanisms research
- Lymphoma Diagnosis and Treatment
- Tissue Engineering and Regenerative Medicine
- Immune cells in cancer
- Hidradenitis Suppurativa and Treatments
- Chronic Lymphocytic Leukemia Research
- Systemic Lupus Erythematosus Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Autophagy in Disease and Therapy
Mayo Clinic in Arizona
2021-2024
Mayo Clinic
2021-2024
WinnMed
2022-2024
University of Iowa Stead Family Children’s Hospital
2018-2020
University of Iowa
2019
Durable response to chimeric antigen receptor T (CART) cell therapy remains limited in part due CART exhaustion. Here, we investigate the regulation of exhaustion with three independent approaches including: a genome-wide CRISPR knockout screen using an vitro model for exhaustion, RNA and ATAC sequencing on baseline exhausted cells, pre-infusion products from responders non-responders ZUMA-1 clinical trial. Each these identify interleukin (IL)-4 as regulator dysfunction. Further, IL-4-treated CD8
In the development of various strategies anti-CD19 immunotherapy for treatment B-cell malignancies, it remains unclear whether CD19 monoclonal antibody therapy impairs subsequent CD19-targeted chimeric antigen receptor T-cell (CART19) therapy. We evaluated potential interference between CD19-targeting tafasitamab and CART19 in preclinical models. Concomitant with showed major binding competition, which led to functional impairment. However, when CD19+ cell lines were pretreated overnight...
The literature on the egress of different herpesviruses after secondary envelopment is contradictory. In this report, we investigated varicella-zoster virus (VZV) in a cell line from child with Pompe disease, glycogen storage disease caused by defect enzyme required for digestion. cells, both late autophagy pathway and mannose-6-phosphate receptor (M6PR) are interrupted. We have postulated that intact autophagic flux higher recoveries VZV infectivity. To test hypothesis, infected cells then...
In humans, the hemochorial placenta is a unique temporary organ that forms during pregnancy to support fetal development, gaseous exchange, delivery of nutrition, removal waste products, and provides immune protection, while maintaining tolerance HLA-haploidentical fetus. this review, we characterize decidual placental immunity maternal viral (co)-infection with HIV-1, human cytomegalovirus (HCMV), Zika virus. We discuss immunology, clinical presentation, epidemiology, before characterizing...
Abstract Despite intensive characterization of immune responses after COVID-19 infection and vaccination, research examining protective correlates vertical transmission in pregnancy are limited. Herein, we profiled humoral cellular characteristics pregnant women infected or vaccinated at different trimesters their corresponding newborns. We noted a significant correlation between spike S1–specific IgG antibody its RBD-ACE2 blocking activity (receptor-binding domain–human...
This study of VZV assembly in the presence bafilomycin A1 emphasizes importance Golgi apparatus/ trans -Golgi network as a platform alphaherpesvirus life cycle. We have previously shown that induces levels autophagy far above basal human skin, major site assembly. The current documented treatment led to impaired capsids after primary envelopment/de-envelopment but before secondary reenvelopment. also complemented prior herpes simplex virus 1 and pseudorabies studies investigating two other...
The goal of this project was to document the autophagy response in human neonatal skin organ culture (SOC) after infection with varicella-zoster virus (VZV). VZV-infected SOC model has attributes herpes zoster, that an injection into is analogous exit from sensory nerve termini during zoster. Cultures were maintained for 28 days and periodically examined by quantitation autophagosomes Imaris software. Expression STAT3 protein plentiful SOC. Abundant observed between 14-28 infection, while...
Abstract While chimeric antigen receptor T-cell therapy targeting CD19 (CART19) has shown remarkable success in the treatment of hematological malignancies, durable response rates remain approximately 40% and there are limited solutions for CART cell solid tumors. To further understand mechanisms resistance, including exhaustion, we employed three independent approaches: 1) RNA ATAC sequencing on unstimulated vs. exhausted healthy donor CART19 cells by utilizing an vitro model 2)...
Abstract Despite the remarkable efficacy of chimeric antigen receptor T -cell therapy (CART) for treatment B-cell malignancies, durable remission remains limited often due to tumor relapse. We have previously demonstrated that tumor-derived extracellular vesicles (EVs) induced CART cell failure in preclinical models. To characterize impact EV dysfunction, we assessed microRNA (miRNA) profiles contained within EVs from two independent patient cohorts and studied how they contributed...
Abstract While chimeric antigen receptor T (CART) cell therapy has shown remarkable success, the development of exhaustion limits durable response. We identified a role for interleukin (IL)-4 in CART through three independent approaches including: 1) genome-wide CRISPR knockout screen using healthy donor cells an vitro model exhaustion, 2) RNA and ATAC sequencing on freshly produced chronically stimulated cells, 3) pre-infusion products from responders non-responders Zuma-1 clinical trial...
Abstract CD19-directed chimeric antigen receptor T (CART19) cell therapy has shown remarkable outcomes in B malignancies and was FDA approved multiple indications, but durable remissions are limited to ~40%. Inhibitory myeloid cells the tumor microenvironment have been found suppress expansion contribute CART19 failure. Here, we studied interactions between monocytes, CART19, understand impact of monocytes on effector functions. First, CD28-costimulated (CART19-28ζ) generated lab from...
Abstract Introduction: Despite the remarkable activity of CD19-directed chimeric antigen receptor T cell therapy (CART19), durable remissions remain low, especially in chronic lymphocytic leukemia (CLL). Ibrutinib is an oral irreversible inhibitor Bruton’s tyrosine kinase and a first line for CLL. Preclinical early clinical data indicate that ibrutinib plus CART19 may be synergistic through inhibition IL2-inducible kinase. To systematically study effects prior treatment on subsequent CART...
<h3>Background</h3> Chimeric antigen receptor T (CART) cell therapy has resulted in impressive overall response rates the treatment of cancer.<sup>1</sup> However, durable to is limited by development exhaustion which impairs CART expansion and persistence.<sup>2</sup> Previously, our group identified IL-4 as a regulator through an evaluation epigenetic changes seen with <i>in vitro</i> model for exhaustion. We then showed that supplementation cells drives exhausted phenotype increase...
Abstract Glioblastoma multiforme (GBM) is the most aggressive and common form of brain tumor, it characterized by an immunosuppressive tumor microenvironment (TME) that supports growth pathology. An integral part GBM stroma mesenchymal stem cells (MSC), which promote growth. Receptor tyrosine kinase EphA3, a member Eph family, overexpressed in tumors MSCs within TME, making attractive target for Chimeric antigen receptor T-cell (CART) therapy. CART has proven incredible promise certain...
Abstract Durable response to chimeric antigen receptor T (CART) cell therapy remains limited in part due CART exhaustion. We investigated the regulation of exhaustion with three independent approaches including: a genome-wide CRISPR knockout screen using validated vitro model for exhaustion, RNA and ATAC sequencing on baseline chronically stimulated cells, pre-infusion products from responders non-responders ZUMA-1 clinical trial. Each these identified IL-4 as key regulator dysfunction....