A5016012336- Neuroinflammation and Neurodegeneration Mechanisms
- Single-cell and spatial transcriptomics
- T-cell and B-cell Immunology
- Systemic Lupus Erythematosus Research
- Stress Responses and Cortisol
- Immune cells in cancer
- Inflammasome and immune disorders
- Immune Response and Inflammation
- Systemic Sclerosis and Related Diseases
- Neuropeptides and Animal Physiology
- Immune Cell Function and Interaction
- Mycobacterium research and diagnosis
- Tryptophan and brain disorders
- Alzheimer's disease research and treatments
- S100 Proteins and Annexins
- Neuroendocrine regulation and behavior
- 3D Printing in Biomedical Research
- Cancer Genomics and Diagnostics
- Dialysis and Renal Disease Management
- Chronic Kidney Disease and Diabetes
- Child Nutrition and Feeding Issues
- Cell Image Analysis Techniques
- interferon and immune responses
- Bacterial Infections and Vaccines
- Signaling Pathways in Disease
Sanofi (United States)
2019-2024
AVEO Oncology (United States)
2024
Massachusetts General Hospital
2017-2022
Inflammation Research Foundation
2019-2021
Duke University
2014-2020
Sanofi (France)
2019
Harvard University
2017-2018
Center for Autism and Related Disorders
2017-2018
Duke Medical Center
2014
University of Nebraska Medical Center
2011-2014
Abstract Evidence suggests many neurological disorders emerge when normal neurodevelopmental trajectories are disrupted, i.e., circuits or cells do not reach their fully mature state. Microglia play a critical role in neurodevelopment and hypothesized to contribute brain disease. We used whole transcriptome profiling with Next Generation sequencing of purified developing microglia identify microglial developmental gene expression program involving thousands genes whose levels change...
Microglia are important innate immune effectors against invading CNS pathogens, such as Staphylococcus aureus (S. aureus), a common etiological agent of brain abscesses typified by widespread inflammation and necrosis. The NLRP3 inflammasome is protein complex involved in IL-1β IL-18 processing following exposure to both pathogen- danger-associated molecular patterns. Although previous studies from our laboratory have established that major cytokine product S. aureus-activated microglia...
Abstract Interleukin‐1β ( IL ‐1β) is essential for eliciting protective immunity during the acute phase of Staphylococcus aureus S. ) infection in central nervous system CNS ). We previously demonstrated that microglial ‐1β production response to live mediated through Nod‐like receptor protein 3 NLRP 3) inflammasome, including adapter ASC (apoptosis‐associated speck‐like containing a caspase‐1 recruitment domain), and pro‐caspase 1. Here, we utilized 3, , caspase 1/11 knockout KO mice...
Abstract Establishing clinically relevant single-cell (SC) transcriptomic workflows from cryopreserved tissue is essential to move this emerging immune monitoring technology the bench bedside. Improper sample preparation leads detrimental cascades, resulting in loss of precious time, money and finally compromised data. There an urgent need establish protocols specifically designed overcome inevitable variations quality uncontrollable factors a clinical setting. Here, we explore techniques...
Early-life conditions can contribute to the propensity for developing neuropsychiatric disease, including substance abuse disorders. However, long-lasting mechanisms that shape risk or resilience drug addiction remain unclear. Previous work has shown a neonatal handling procedure in rats (which promotes enriched maternal care) attenuates morphine conditioning, reduces morphine-induced glial activation, and increases microglial expression of anti-inflammatory cytokine interleukin-10 (IL-10)....
ABSTRACT Autoimmune diseases are a major cause of mortality 1,2 . Current treatments often yield severe insult to host tissue. It is hypothesized that improved “precision medicine” therapies will target pathogenic cells selectively and thus reduce or eliminate side effects, potentially induce robust immune tolerance 3 However, it remains challenging systematically identify which cellular phenotypes present in ensembles. Here, we novel machine learning approach, Signac, uses neural networks...
The classification of immune cell phenotypes in single data is a major challenge biology research today. Here, we present novel machine learning approach, SignacX, which uses neural networks trained with flowsorted gene expression to classify cellular RNA-sequencing data. We demonstrate that SignacX accurately classified across diseases, technologies, species, and tissues, outperformed other leading methods phenotype classification, particularly for CD8 CD4 T subsets. used the annotations...
Kidney damage and dysfunction is an emerging health issue worldwide resulting in high morbidity mortality rates. Numerous renal diseases are recognized to be driven by the immune system. Despite this recognition, development of targeted therapies has been challenging as knowledge underlying mechanism complex interactions remains insufficient. Recent advancements field offer promising avenues for exploring interplay between cells their role inflammation diseases. This study describes...
Abstract Decreases in social behavior are a hallmark aspect of acute “sickness behavior” response to infection. However, immune insults that occur during the perinatal period may have long-lasting consequences for adult by impacting developmental organization underlying neural circuits. Microglia, resident cells central nervous system, sensitive stimulation and play critical role sculpting circuits, making them likely mediators this process. Here, we investigated impact postnatal day (PND) 4...
Abstract Autoimmune diseases are a major cause of mortality1,2. Current treatments often yield severe insult to host tissue. It is hypothesized that improved therapies will target pathogenic cells selectively and thus reduce or eliminate side effects, potentially induce robust immune tolerance3. However, it remains challenging systematically identify which cellular phenotypes present in ensembles. Here, we novel machine learning approach, Signac, uses neural networks trained with flow-sorted...
Abstract Kidney damage and dysfunction is an emerging health issue worldwide resulting in high morbidity mortality rates. Numerous renal diseases are recognized to be driven by the immune system. Despite this recognition, development of targeted therapies has been challenging as knowledge underlying mechanism complex interactions remains insufficient. Recent advancements field offer promising avenues for exploring interplay between cells their role inflammation diseases. This study describes...
Abstract Establishing clinically relevant single-cell (SC) transcriptomic workflows from cryopreserved tissue is essential to move this emerging immune monitoring technology the bench bedside. Improper sample preparation leads detrimental cascades, resulting in loss of precious time, money and finally compromised data. There an urgent need establish protocols specifically designed overcome inevitable variations quality uncontrollable factors a clinical setting. Here, we explore techniques...