A5039457202- Immune Cell Function and Interaction
- CAR-T cell therapy research
- T-cell and B-cell Immunology
- RNA Interference and Gene Delivery
- Viral-associated cancers and disorders
- Cytomegalovirus and herpesvirus research
- T-cell and Retrovirus Studies
- Advancements in Semiconductor Devices and Circuit Design
- CRISPR and Genetic Engineering
- Immunotherapy and Immune Responses
- Hematopoietic Stem Cell Transplantation
- Neonatal Respiratory Health Research
- Nanowire Synthesis and Applications
- Sleep and Wakefulness Research
- Pesticide Exposure and Toxicity
- Hydrogen's biological and therapeutic effects
- Silicon Carbide Semiconductor Technologies
- Mesenchymal stem cell research
- Nanoparticle-Based Drug Delivery
- Immune cells in cancer
- MicroRNA in disease regulation
- Monoclonal and Polyclonal Antibodies Research
- Developmental Biology and Gene Regulation
- Chronic Myeloid Leukemia Treatments
- Single-cell and spatial transcriptomics
The Ohio State University Wexner Medical Center
2024
Nationwide Children's Hospital
2018-2023
Baylor College of Medicine
2015-2019
Texas Children's Hospital
2015-2017
Houston Methodist
2015-2017
Methodist Hospital
2015-2017
Neurological Research Institute
2017
Children's Cancer Center
2017
Hippocampal neural stem cells (NSCs) integrate inputs from multiple sources to balance quiescence and activation. Notch signaling plays a key role during this process. Here, we report that Lunatic fringe (Lfng), modifier of the receptor, is selectively expressed in NSCs. Further, Lfng NSCs ligands Delta1 Jagged1, by their progeny, together influence NSC recruitment, cell cycle duration, terminal fate. We propose new model which Lfng-mediated enables direct communication between its...
CRISPR/Cas9 technology is accelerating genome engineering in many cell types, but so far, gene delivery and stable modification have been challenging primary NK cells. For example, transgene using lentiviral or retroviral transduction resulted a limited yield of genetically-engineered cells due to substantial procedure-associated apoptosis. We describe here DNA-free method for editing human expanded Cas9 ribonucleoprotein complexes (Cas9/RNPs). This allowed efficient knockout the TGFBR2...
Abstract Natural killer (NK)‐cells have potent anti‐tumor effects, yet it remains unclear if they are effective for patients with relapsed acute myeloid leukemia (AML). In a phase I clinical trial, we treated 12 (median age 60 years) refractory AML 5 lines of prior therapy, median bone marrow blast count 47%) fludarabine/cytarabine followed by 6 infusions NK‐cells expanded from haploidentical donors using K562 feeder cells expressing membrane‐bound IL21 and 4‐1BBL. Patients received 10 –10 7...
Transforming growth factor-beta (TGFβ) is a potent immunosuppressive cytokine that inhibits the anti-tumor responses of NK cells and T cells. However, stimulation natural killer (NK) with pro-inflammatory cytokines decreases cell sensitivity to TGFβ. Herein, we sought determine if TGFβ imprinting (TGFβi) during activation expansion would decrease suppression. To this end, demonstrate chronic IL-2 TGFβi potently induces hypersecretion interferon-gamma (IFNγ) tumor necrosis factor-alpha (TNFα)...
Abstract T cells expressing CD19-specific chimeric antigen receptors (CARs) with endodomains that encode a signaling domain derived from CD3ζ and CD28 or 41BB have potent antitumor activity in early-phase clinical studies for B-cell malignancies. Besides CARs, other approaches are actively being pursued to redirect CD19, including recombinant bispecific T-cell engager (BiTE) proteins genetically modified express BiTEs [engager (ENG) cells]. As provide no costimulation, we investigated here...
The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that regulates cellular processes in cancer and immunity, including innate immune cell development effector function. However, the transcriptional repertoire through which AHR mediates these effects remains largely unexplored. To elucidate elements directly regulated by natural killer (NK) cells, we performed RNA chromatin immunoprecipitation sequencing on NK cells exposed to agonist or antagonist. We show mature...
CRISPR/Cas9 technology is accelerating genome engineering in many cell types, but so far, gene delivery and stable modification have been challenging primary NK cells. For example, transgene using lentiviral or retroviral transduction resulted a limited yield of genetically-engineered cells due to substantial procedure-associated apoptosis. We describe here DNA-free method for editing human expanded Cas9 ribonucleoprotein complexes (Cas9/RNPs). This allowed efficient knockout the TGFBR2...
Loss of cytotoxicity and defective metabolism are linked to glycogen synthase kinase 3 beta (GSK3β) overexpression in natural killer (NK) cells from patients with acute myeloid leukemia or healthy donors after expansion ex vivo IL-15. Drug inhibition GSK3β these NK improves their maturation cytotoxic activity, but the mechanisms GSK3β-mediated dysfunction have not been well studied. Here, we show that feeder expressing membrane-bound IL-21 maintained normal levels, allowing us study function...
Meeting abstracts Immunotherapy with T cells or bispecific cell engagers is one promising approach to improve outcomes for patients CD19-positive hematological malignancies. We had previously shown that expressing recognize CD19 and CD3 (CD19-ENG
Respiratory system damage is the primary cause of mortality in individuals who are exposed to vesicating agents including sulfur mustard (SM). Despite these devastating health complications, there no fielded therapeutics that specific for such injuries. Previous studies reported SM inhalation depleted tracheobronchial airway epithelial stem cell (TSC) pool and supported hypothesis, TSC replacement will restore integrity improve outcomes SM-exposed individuals. express Major...
Although autologous or donor-derived EBV-specific T cells (EBVSTs) have clinical efficacy for Hodgkin and non-Hodgkin lymphoma, the lengthy manufacturing process anergy of patient tumor-specific reduce feasibility widespread use. An alternative approach is establishment a pre-made third party bank that can provide access to EBVSTs almost any patient. We previously evaluated multivirus-specific third-party refractory viral infections after HSCT. Of 50 recipients, 74% responded, even when were...
Although donor-derived EBV-specific T cells (EBVSTs) have clinical efficacy for EBV+ lymphoma, the lengthy manufacture process reduces feasibility of immediate use. An alternative approach is establishment a pre-made third party bank that can provide access to EBVSTs almost any patient. established banks consist primarily donors from marrow registries or family members according HLA genotype, significant limitation this generation lines with limited specificity targeted antigens through...
<p>S1: T-cell immunophenotyping by flow cytometry. S2: Determination of TSCM presence in PBMC and NT T-cells S3: CD19-ENGT-cells expressing CD80 and/or 41BBL kill Nalm 6 cells efficiently. S4: Experimental set up Serial Killing Assay. S5: CD19- ENG.41BBL/CD80 have improved ability to sequentially CD19 target cells. S6: CD19-ENG or S7: express PD-L1 after exposure IFNgamma. S8: expand vivo persist long-term at low levels.</p>
<div>Abstract<p>T cells expressing CD19-specific chimeric antigen receptors (CARs) with endodomains that encode a signaling domain derived from CD3ζ and CD28 or 41BB have potent antitumor activity in early-phase clinical studies for B-cell malignancies. Besides CARs, other approaches are actively being pursued to redirect T CD19, including recombinant bispecific T-cell engager (BiTE) proteins genetically modified express BiTEs [engager (ENG) cells]. As provide no costimulation,...
<p>S1: T-cell immunophenotyping by flow cytometry. S2: Determination of TSCM presence in PBMC and NT T-cells S3: CD19-ENGT-cells expressing CD80 and/or 41BBL kill Nalm 6 cells efficiently. S4: Experimental set up Serial Killing Assay. S5: CD19- ENG.41BBL/CD80 have improved ability to sequentially CD19 target cells. S6: CD19-ENG or S7: express PD-L1 after exposure IFNgamma. S8: expand vivo persist long-term at low levels.</p>
<div>Abstract<p>T cells expressing CD19-specific chimeric antigen receptors (CARs) with endodomains that encode a signaling domain derived from CD3ζ and CD28 or 41BB have potent antitumor activity in early-phase clinical studies for B-cell malignancies. Besides CARs, other approaches are actively being pursued to redirect T CD19, including recombinant bispecific T-cell engager (BiTE) proteins genetically modified express BiTEs [engager (ENG) cells]. As provide no costimulation,...