A5079139261- CAR-T cell therapy research
- Systemic Lupus Erythematosus Research
- Immunotherapy and Immune Responses
- Glioma Diagnosis and Treatment
- Viral gastroenteritis research and epidemiology
- Cancer Research and Treatments
- Virus-based gene therapy research
- Respiratory viral infections research
- Cancer Immunotherapy and Biomarkers
- Cell Image Analysis Techniques
- T-cell and B-cell Immunology
- Viral Infections and Immunology Research
- Image Processing Techniques and Applications
- Immune Cell Function and Interaction
- Atherosclerosis and Cardiovascular Diseases
- Radiomics and Machine Learning in Medical Imaging
- CRISPR and Genetic Engineering
- Pediatric health and respiratory diseases
- RNA Interference and Gene Delivery
- Inflammatory Bowel Disease
- Pneumonia and Respiratory Infections
- 3D Printing in Biomedical Research
- Digital Imaging for Blood Diseases
- Phagocytosis and Immune Regulation
- Monoclonal and Polyclonal Antibodies Research
Evalueserve (India)
2024
University of Chicago
2020-2023
University of Florida
2016-2022
Allen Institute for Brain Science
2016-2020
Public Works Department Buildings and Roads
1996
The University of Texas Medical Branch at Galveston
1992-1994
BACKGROUNDIn human lupus nephritis (LN), tubulointerstitial inflammation (TII) on biopsy predicts progression to end-stage renal disease (ESRD). However, only about half of patients with moderate-to-severe TII develop ESRD. We hypothesized that this heterogeneity in outcome reflects different underlying inflammatory states. Therefore, we interrogated biopsies from LN longitudinal and cross-sectional cohorts.METHODSData were acquired using conventional highly multiplexed confocal microscopy....
Fecal shedding of virulent revertant polioviruses was examined in isolates from infants previously immunized with ⩾ 1 dose orally administered live attenuated polio vaccine (OPV) alone, enhanced-potency inactivated (EIPV) or a combination both. After administration OPV poliovirus serotypes were recovered feces within week and for as long 31–60 days 30%–80% subjects after 2 doses 30%–50% immunization ⩾3 doses. No observed challenge OPV. However, fecal OPY 50%–100% the EIPV. These findings...
Immune checkpoint blockade using anti-PD-1 monoclonal antibodies has shown considerable promise in the treatment of solid tumors, but brain tumors remain notoriously refractory to treatment. In CNS malignancies that are completely resistant PD-1 blockade, we found bone marrow-derived, lineage-negative hematopoietic stem and progenitor cells (HSCs) express C-C chemokine receptor type 2 (CCR2+) reverses resistance sensitizes mice curative immunotherapy. HSC transfer with increases T-cell...
Immunotherapy has been demonstrably effective against multiple cancers, yet tumor escape is common. It remains unclear how brain tumors immunotherapy and to overcome this immune escape.
Groups of infants were immunized with one or two doses orally inoculated live attenuated Sabin poliovirus vaccine (OPV group) enhanced-potency inactivated (EIPV) administered parenterally followed by OPV (EIPV-OPV group). The fecal specimens from both groups tested for shedding 1–2 months after OPV. virus isolates examined nucleic acid sequences in the 5′ noncoding regions (bases 480, 481, and 472 serotypes 1,2, 3, respectively) to determine whether viruses shed represented nonattenuated...
Purpose: Adoptive T-cell immunotherapy (ACT) has emerged as a viable therapeutic for peripheral and central nervous system (CNS) tumors. In cancers, optimal efficacy of ACT is reliant on dendritic cells (DCs) in the tumor microenvironment. However, CNS largely devoid resident migratory DCs to function antigen-presenting during immunotherapy. Herein, we demonstrate that cellular interactions between adoptively transferred tumor-reactive T bone marrow-derived hematopoietic stem progenitor...
This report describes a rapid method of detection poliovirus from viral isolates clinical specimens using single set primers selected the conserved 5' noncoding region genome. Of 144 examined, 81 were positive for polioviruses and 50 nonpoliovirus enteroviruses by tissue culture neutralization infectivity. All (100%) identified as infectivity also polymerase chain reaction. enterovirus found to be negative infectivity, 48 The high sensitivity specificity (96%) primer indicate that this assay...
Extensive clonal T cell expansion is associated with response to immunotherapy.
Systemic lupus erythematosus (SLE) is a complex, systemic autoimmune disease with many clinical presentations including nephritis (LuN), or chronic inflammation of the kidneys. Current therapies for SLE are only modestly effective, highlighting need to better understand networks immune cells in and LuN. In this work, we assess performance two convolutional neural network (CNN) architectures –Mask R-CNN U-Net— task instance segmentation 5 immune-cell classes 31 LuN biopsies. Each biopsy was...
Significance: Lupus nephritis (LuN) is a chronic inflammatory kidney disease. The cellular mechanisms by which LuN progresses to failure are poorly characterized. Automated instance segmentation of immune cells in immunofluorescence images can probe these interactions. Aim: Our specific goal quantify how sample fixation and staining panel design impact automated characterization cells. Approach: Convolutional neural networks (CNNs) were trained segment fluorescence confocal biopsies. Three...
Deep convolutional neural networks (CNNs) have demonstrated high accuracy in a wide range of computer vision applications, including medical and biological imaging. Many CNNs are fully supervised learning algorithms, their performance is directly associated with the quality training data labels, which human-defined. In this work, we investigate fidelity human-defined truth for cell detection, segmentation, classification tasks multiplex microscopy images. We compare manual annotations from...
In human lupus nephritis, tubulointerstitial inflammation (TII) is associated with in situ expansion of B cells expressing anti-vimentin antibodies (AVAs). The mechanism by which AVAs are selected unclear. Herein, we demonstrate that AVA somatic hypermutation (SHM) and selection increase affinity for vimentin. Indeed, germline reversion several demonstrated higher can be from both low cell clones even those strongly reactive other autoantigens. While maturation, enzyme-linked immunosorbent...
Computer vision and deep learning are integral tools in the improvement of high-throughput analysis cellular images. Specifically, optimization algorithms for object detection instance segmentation tasks important image to segment classify multi-object, multi-class In this work, we employ an pipeline with Mask RCNN, using a ResNet-101 Feature Pyramid Network convolutional backbone T cells antigen presenting (APCs) multi-channel fluorescence confocal images lupus nephritis biopsies. This task...
We demonstrate an instance segmentation method with Mask R-CNN using a ResNet-101 plus Feature Pyramid Network convolutional backbone to segment and classify T cells antigen presenting (APCs) in multi-channel fluorescence confocal images. This network improves on our previous cell distance mapping (CDM) pipeline, which used custom 10- layer neural for segmentation. have validated two independent datasets of images: 1) mouse lymph node tissue, 2) human lupus nephritis (LuN) biopsies. For...
Several disease states, including cancer and autoimmunity, are characterized by the infiltration of large populations immune cells into organ tissue. The degree composition these invading have been correlated with patient outcomes, suggesting that intercellular interactions occurring in inflamed tissue play a role pathology. Immunofluorescence staining paired confocal microscopy produce detailed visualizations interactions. Applying computer vision machine learning methods to resulting...
ABSTRACT In human lupus nephritis, tubulointerstitial inflammation (TII) is associated with in situ expansion of B cells expressing anti-vimentin antibodies (AVAs). The mechanism by which AVAs are selected unclear. Herein, we demonstrate that AVA somatic hypermutation and selection increase affinity for vimentin. However, enzyme-linked immunosorbent assays (ELISAs) suggested maturation might be a non-specific consequence increasing polyreactivity. Subsequent multi-color confocal microscopy...
Triple-negative breast cancer (TNBC) is an aggressive subtype of defined by the lack hormone receptor overexpression. TNBC patients are at a higher risk recurrence than with other cancers. As this disease disproportionally affects young women color, there urgent need to address health inequity improving detection, prognostication, and therapy guidance. Currently, expected have better prognosis if biopsy analysis shows more tumor-infiltrating immune cells. However, immunotherapies such as...
Good clinical outcomes in response to adoptive cellular therapies are correlated with anti-tumor function, intratumoral migration, and persistence of adoptively transferred tumor-specific T cells. Our group has developed a highly efficacious cell therapy (ACT) against intracranial glioma that meets these criteria. Further evaluation our platform reveals ACT also primes host-derived cells, OBJECTIVE is demonstrate this phenomenon required for efficacy immunotherapy. We employ bone...
Triple-negative breast cancer (TNBC) is defined by a lack of biomarkers in the tumor. This inherent targets results effective therapeutic tools. However, immunotherapies have shown promise treating TNBC. Here, we present computer vision methods for automatic detection immune cells and larger structures We demonstrate accurate cell segmentation highly-multiplexed, whole-slide images TNBC biopsies. Additionally, show preliminary spatial analyses that identify characterize tertiary lymphoid...