A5072437082- CAR-T cell therapy research
- Immune Cell Function and Interaction
- Lipid Membrane Structure and Behavior
- Silicon Carbide Semiconductor Technologies
- Mycobacterium research and diagnosis
- T-cell and B-cell Immunology
- Immune cells in cancer
- Advancements in Semiconductor Devices and Circuit Design
- Sphingolipid Metabolism and Signaling
- Immunotherapy and Immune Responses
- Blood donation and transfusion practices
- Cancer Research and Treatments
- Endoplasmic Reticulum Stress and Disease
- Adenosine and Purinergic Signaling
- Organ Transplantation Techniques and Outcomes
- Cell Image Analysis Techniques
- Pneumocystis jirovecii pneumonia detection and treatment
- Lipid metabolism and biosynthesis
- Blood transfusion and management
- CRISPR and Genetic Engineering
- Tuberculosis Research and Epidemiology
- Cellular transport and secretion
St. Jude Children's Research Hospital
2020-2024
Kent State University
2022-2023
University of Cincinnati Medical Center
2019-2022
Cincinnati Children's Hospital Medical Center
2017-2022
University of Cincinnati
2017-2019
Universitätsmedizin Göttingen
1996
The efficacy of adoptive T cell therapies for cancer treatment can be limited by suppressive signals from both extrinsic factors and intrinsic inhibitory checkpoints1,2. Targeted gene editing has the potential to overcome these limitations enhance therapeutic function3-10. Here we performed multiple genome-wide CRISPR knock-out screens under different immunosuppressive conditions identify genes that targeted prevent dysfunction. These converged on RASA2, a RAS GTPase-activating protein...
Abstract The inability of chimeric antigen receptor (CAR) T cells to sustain their effector function after repeated exposure tumor is a major obstacle success in patients with solid tumors. To overcome this limitation, we designed novel cytokine create an autocrine loop that links activation-dependent GM-CSF production by CAR IL18 signaling (GM18). Expression GM18 enhanced antigen- and manner. In repeat stimulation assays, which mimic chronic exposure, CAR.GM18 had significantly greater...
Immunonutrition as a therapeutic approach is rapidly gaining interest in the fight against infection. Targeting l-arginine metabolism intriguing, considering this amino acid substrate for antimicrobial NO production by macrophages. The importance of during infection supported finding that inhibiting its synthesis from precursor l-citrulline blunts host defense. During first few weeks following pulmonary mycobacterial infection, we found drastic increase lung, even though serum concentrations...
Activation, recruitment, and effector function of T lymphocytes are essential for control mycobacterial infection. These processes tightly regulated in cells by the availability l-arginine within microenvironment. In turn, infection dampens cell responsiveness through arginase induction myeloid cells, promoting sequestration local milieu. Here, we show can replenish intracellular metabolism l-citrulline to mediate inflammatory function, allowing anti-mycobacterial overcome arginase-mediated...
Metabolomics analyses suggest changes in amino acid abundance, particularly l-arginine (L-ARG), occur patients with tuberculosis. Immune cells require L-ARG to fuel effector functions following infection. We have previously described an synthesis pathway immune cells; however, its role APCs has yet be uncovered. Using a coculture system mycobacterial-specific CD4
Diacylglycerol pyrophosphate (DGPP) is an anionic phospholipid formed in plants, yeast, and parasites under multiple stress stimuli. It synthesized by the phosphorylation action of phosphatidic acid (PA) kinase on acid, a signaling lipid with multifunctional properties. PA functions membrane through interaction its negatively charged phosphomonoester headgroup positively proteins ions. DGPP, like PA, can interact electrostatically via electrostatic-hydrogen bond switch mechanism but differs...
<h3>Background</h3> A critical limitation for solid tumor CAR T cell therapy is the lack of safe, targetable antigens. Splice variants extracellular matrix proteins provide a unique class protein candidates chimeric antigen therapy. One such target, oncofetal Tenascin C, was previously identified having high expression in tissues as osteosarcoma (OS) and glioma.<sup>1</sup> Here, we evaluate cells redirected to alternatively spliced C domain (C.TNC). <h3>Methods</h3> Using RTqPCR IHC assays,...
Abstract Immunotherapy in the form of chimeric antigen receptor (CAR) T cells has emerged as a promising treatment option for various cancers following its success B cell hematological malignancies. However, solid tumor microenvironment (TME) presented many challenges to CAR efficacy and persistence, part due lack cell-supportive cytokines at site. We hypothesized that we could improve infusion by engineering self-sustaining cytokine would fuel TME. One is abundantly produced upon...