- T-cell and B-cell Immunology
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- Cancer Immunotherapy and Biomarkers
- Lymphoma Diagnosis and Treatment
- CRISPR and Genetic Engineering
- Monoclonal and Polyclonal Antibodies Research
- Cell Image Analysis Techniques
- 3D Printing in Biomedical Research
- Molecular Biology Techniques and Applications
- Cellular Mechanics and Interactions
- Carcinogens and Genotoxicity Assessment
- Cell Adhesion Molecules Research
- HIV/AIDS Research and Interventions
- Cancer Cells and Metastasis
- RNA Research and Splicing
- Genetics, Bioinformatics, and Biomedical Research
- Chemokine receptors and signaling
- Virus-based gene therapy research
- Cancer Mechanisms and Therapy
- Single-cell and spatial transcriptomics
- CNS Lymphoma Diagnosis and Treatment
- Electrospun Nanofibers in Biomedical Applications
- Tissue Engineering and Regenerative Medicine
Columbia University Irving Medical Center
2022-2025
Columbia University
2022-2024
Cornell University
2016-2023
Royal College of Physicians
2023
Columbia College
2023
Boston University
2017
Saint Meinrad Seminary and School of Theology
2017
Abstract Molecular alterations in the histone methyltransferase EZH2 and antiapoptotic protein Bcl-2 frequently co-occur diffuse large B-cell lymphoma (DLBCL). Because DLBCL tumors with these characteristics are likely dependent on both oncogenes, dual targeting of is a rational therapeutic approach. We hypothesized that inhibition would be synergistic DLBCL. To test this, we evaluated inhibitor tazemetostat venetoclax cells, 3-dimensional organoids, patient-derived xenografts (PDXs). found...
The role of microenvironment-mediated biophysical forces in human lymphomas remains elusive. Diffuse large B cell (DLBCLs) are heterogeneous tumors, which originate from highly proliferative germinal center cells. These their associated neo-vessels, and lymphatics presumably expose cells to particular fluid flow survival signals. Here, we show that enhances proliferation modulates response DLBCLs specific therapeutic agents. Fluid upregulates surface expression receptors (BCRs) integrin...
Glycoengineered bacteria have emerged as a cost-effective platform for rapid and controllable biosynthesis of designer conjugate vaccines. However, little is known about the engagement such conjugates with naı̈ve B cells to induce formation germinal centers (GC), subanatomical microenvironment that converts into antibody-secreting plasma cells. Using three-dimensional biomaterials-based B-cell follicular organoid system, we demonstrate triggered robust expression hallmark GC markers, cell...
Abstract Chromosomal instability (CIN) is a hallmark of cancer that drives metastasis, immune evasion and treatment resistance. CIN results from chromosome mis-segregation events during anaphase, as excessive chromatin packaged in micronuclei (MN), can be enumerated to quantify CIN. Despite recent advancements automation through computer vision machine learning, the assessment remains predominantly manual time-consuming task, thus hampering important work field. Here, we present micronuclAI...
Germinal centers are dynamic structures within lymphoid tissues, which develop once B cells receive activating signals from surrounding immune cells. center small in number, heterogeneous, and prone to rapid apoptosis unless selected by the body form memory Despite extensive research cell differentiation process, role of niche, particular integrin ligands, development early germinal center-like phenotype remains unclear. Here, we report a biomaterials-based modular organoid that enables...
Chromosomal instability (CIN) is a hallmark of cancer that drives metastasis, immune evasion and treatment resistance. CIN may result from chromosome mis-segregation errors excessive chromatin frequently packaged in micronuclei (MN), which can be enumerated to quantify CIN. The assessment remains predominantly manual time-consuming task. Here, we present micronuclAI, pipeline for automated reliable quantification MN varying size morphology cells stained only DNA. micronuclAI achieve close...
In arterial tissue engineering, mimicking native structure and mechanical properties is essential because compliance mismatch can lead to graft failure further disease. With bottom-up engineering approaches, designing components with proper microscale crucial achieve the necessary macroscale in final implant. This study develops a thermoresponsive cell culture platform for growing aligned vascular smooth muscle (VSMC) sheets by photografting N-isopropylacrylamide (NIPAAm) onto micropatterned...
ABSTRACT The cell autonomous balance of immune-inhibitory and -stimulatory signals is a critical yet poorly understood process in cancer immune evasion. Using patient-derived co-culture models humanized mouse models, we show that an intact CD58:CD2 interaction necessary for anti-tumor immunity. Defects this axis lead to multi-faceted evasion through impaired CD2-dependent T polyfunctionality, exclusion, intra-tumoral proliferation, concurrent protein stabilization PD-L1. We performed...
Abstract Base editing enables precise generation of single nucleotide variants, but large-scale screening in primary human T cells has been limited by low efficiency. Here, we developed a high-throughput approach for highly efficient, massively parallel adenine and cytosine base-editor cells. We performed multiple pooled screens 108 genes with central functions whole-gene tiling mutagenesis selected genes. All were functionally read out to capture the effect variants on hallmarks cell...
Abstract B cells undergo affinity maturation to T cell-dependent antigens within specialized microenvironments in secondary lymphoid organs termed germinal centers (GCs) resulting the selective proliferation and differentiation of high-affinity cells. Selection is driven by ability antigen-specific GC extract antigen presented on follicular dendritic subsequently recruit stimuli from helper Successful ultimately differentiate into plasma that secrete large amounts antibody, or memory...
ABSTRACT Base editing enables generation of single nucleotide variants, but large-scale screening in primary human T cells is limited due to low efficiency, among other challenges 1 . Here, we developed a high-throughput approach for high-efficiency and massively parallel adenine cytosine base-editor cells. We performed multiple screens 102 genes with central functions full-length tiling mutagenesis selected genes, read out variant effects on hallmarks cell anti-tumor immunity, including...
Abstract Molecular alterations in the histone methyltransferase EZH2 and antiapoptotic protein BCL2 frequently co-occur diffuse large B-cell lymphoma (DLBCL). We hypothesized that inhibition would be synergistic DLBCL. To test this, we evaluated inhibitor tazemetostat venetoclax DLBCL cells, 3D organoids, patient-derived xenografts (PDXs). found are cells harbor both an mutation a BCL2/IGH translocation, as demonstrated by CI values <1 (CI: 0.034, 0.259 0.074 SUDHL-6, WSU-DLCL2,...