A5048189143- CAR-T cell therapy research
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Monoclonal and Polyclonal Antibodies Research
- Glycosylation and Glycoproteins Research
- Histone Deacetylase Inhibitors Research
- T-cell and B-cell Immunology
- Innovative Microfluidic and Catalytic Techniques Innovation
- Galectins and Cancer Biology
- Nanoparticle-Based Drug Delivery
- Nuclear Receptors and Signaling
- Epigenetics and DNA Methylation
- Microfluidic and Bio-sensing Technologies
- CRISPR and Genetic Engineering
- Cholesterol and Lipid Metabolism
- Single-cell and spatial transcriptomics
- Virus-based gene therapy research
- HIV Research and Treatment
- Microfluidic and Capillary Electrophoresis Applications
- RNA Interference and Gene Delivery
- Nanofabrication and Lithography Techniques
Johns Hopkins University
2020-2025
Johns Hopkins Medicine
2020-2025
University of Baltimore
2021-2024
Mayo Clinic in Arizona
2022
WinnMed
2021
University of Illinois Urbana-Champaign
2020
Urbana University
2020
Techniques to analyze and sort single cells based on functional outputs, such as secreted products, have the potential transform our understanding of cellular biology well accelerate development next-generation cell antibody therapies. However, molecules rapidly diffuse away from cells, analysis these products requires specialized equipment expertise compartmentalize individual capture their secretions. Herein, we describe methods fabricate hydrogel-based chemically functionalized...
Background Natural Killer (NK) cells have intrinsic anticancer activity that can be redirected toward acute myeloid leukemia (AML) with chimeric antigen receptor (CAR) engineering. Here, we study the functional consequences of CAR binding affinity and targeted epitope on CAR-NK cell activation, cytolytic synapse formation, antitumor activity. Methods We characterized NK-92 primary NK populations expressing variant AML-specific CARs containing single-chain variable fragments (scFvs, 26292 or...
Significance CAR T cells have shown significant promise in treating hematopoietic cancers but challenges remain, including antigen loss and identification of targets solid tumors. Aberrant O-linked glycosylation is common, often resulting expression cell-surface neoantigens. We used directed evolution to engineer the binding site an antibody so variants reacted more broadly with tumor-specific glycoprotein epitopes containing Tn (GalNAc-O-S/T). As CARs, these showed improved broader activity...
After antigenic activation, quiescent naive CD4 + T cells alter their metabolism to proliferate. This metabolic shift increases production of nucleotides, amino acids, fatty and sterols. Here, we show that histone deacetylase 3 (HDAC3) is critical for activation murine peripheral cells. HDAC3-deficient failed proliferate blast after in vitro TCR/CD28 stimulation. Upon T-cell genes involved cholesterol biosynthesis are upregulated while promote efflux repressed. had reduced levels cellular...
Abstract Techniques to analyze and sort single cells based on functional outputs, such as secreted products, have the potential transform our understanding of cellular biology, well accelerate development next generation cell antibody therapies. However, molecules rapidly diffuse away from cells, analysis these products requires specialized equipment expertise compartmentalize individual capture their secretions. Herein we demonstrate use suspendable microcontainers viable at high-throughput...
Inhibitory receptors have a critical role in the regulation of immunity. Siglecs are family primarily inhibitory expressed by immune cells that recognize specific sialic acid modifications on cell surface glycans. Many tumors increased incorporation. Overexpression sialyltransferase ST8Sia6 led to altered responses and tumor growth. In this study, we examined regulating antitumor knockout mice had an enhanced response tumors. The loss promoted intratumoral activation macrophages dendritic...
Abstract Acute myeloid leukemia (AML) is a highly prevalent blood and bone marrow cancer characterized by the uncontrolled growth of abnormal myeloblasts. Current treatments for AML often result in systemic toxicities patients, many whom will still experience relapse. There thus an unmet need to develop safer more effective therapies targeting AML. Chimeric antigen receptor (CAR) T cells, which are engineered express cancer-targeting extracellular antibody single-chain variable fragment...
Abstract Engineered cell therapies, especially chimeric antigen receptor (CAR) T have shown much promise in treating various cancers, most notably hematologic malignancies. However, the success of these therapies is highly variable between cancer types and across patient populations. A growing body literature suggests that certain functional properties are key drivers response; thus, it imperative to develop a more thorough understanding heterogeneity populations order inform design next...
Abstract Chimeric antigen receptors (CARs) have shown remarkable promise in treating hematological malignancies, especially those expressing CD19 antigen. On the other hand, identification and efficacy of CARs against antigens solid cancers has remained a significant challenge. Defects glycosylation are common, can result formation cell surface-expressed neoantigens that aberrantly glycosylated. Here, we focused on from defects O-linked glycosylation, leading to unique possess an...
Abstract Inhibitory receptors have a critical role in the regulation of immunity. Siglecs are family primarily inhibitory expressed by immune cells, which recognize specific sialic acid modifications on cell surface glycans. Sialyltransferases enzymes that catalyzing addition acids onto glycoproteins and glycolipids. Siglec-E binds to α2,8-linked disialic acids, generated enzyme ST8Sia6 O-linked functions inhibit activation innate cells. Many tumors increased incorporation. Overexpression...
Abstract Acute myeloid leukemia (AML) is a highly prevalent blood and bone marrow cancer characterized by the uncontrolled growth of abnormal myeloblasts. Current treatments for AML often result in systemic toxicities patients, many whom will still experience relapse. There thus an unmet need to develop safer more effective therapies targeting AML. Chimeric antigen receptor (CAR) T cells, which are engineered express cancer-targeting extracellular antibody single-chain variable fragment...
Abstract After activation, CD4+ T cells undergo metabolic modifications in order to orchestrate successful immune responses. In particular, naïve shift a more glycolysis-heavy program that produces the necessary metabolites for growth, division, and exertion of effector function. Histone Deacetylase 3 (HDAC3) has been shown epigenetically regulate many cell fate decisions is also capable post-translationally modifying non-histone proteins. Deletion HDAC3 mature using distal Lck-Cre cKO mouse...