- Sepsis Diagnosis and Treatment
- Immune Response and Inflammation
- COVID-19 Clinical Research Studies
- SARS-CoV-2 and COVID-19 Research
- Adrenal Hormones and Disorders
- Long-Term Effects of COVID-19
- Kawasaki Disease and Coronary Complications
- Asthma and respiratory diseases
- Thermal Regulation in Medicine
- Inflammasome and immune disorders
- Immune Cell Function and Interaction
- Pericarditis and Cardiac Tamponade
- Vasculitis and related conditions
- Immunotherapy and Immune Responses
- Coronary Artery Anomalies
- Platelet Disorders and Treatments
- Heme Oxygenase-1 and Carbon Monoxide
- Extracellular vesicles in disease
- Hemoglobin structure and function
- Inflammation biomarkers and pathways
- Sperm and Testicular Function
- Inflammatory Biomarkers in Disease Prognosis
- Artificial Intelligence in Healthcare and Education
- Pathogenesis and Treatment of Hiccups
- Erythrocyte Function and Pathophysiology
Rainbow Babies & Children's Hospital
2022-2025
Case Western Reserve University
2022-2024
University School
2023-2024
University Hospitals of Cleveland
2022-2024
Washington University in St. Louis
2018-2023
Pediatrics and Genetics
2020
McGill University Health Centre
2010-2011
Christie (Canada)
2007-2010
McGill University
2005-2007
Montreal Children's Hospital
2005
COVID-19-associated morbidity and mortality have been attributed to a pathologic host response. Two divergent hypotheses proposed: hyperinflammatory cytokine storm; failure of protective immunity that results in unrestrained viral dissemination organ injury. A key explanation for the inability address this controversy has lack diagnostic tools evaluate immune function COVID-19 infections. ELISpot, highly sensitive, functional immunoassay, was employed 27 patients with COVID-19, 51 sepsis, 18...
Sepsis, a disease of divergent pro- and anti-inflammatory-mediated pathways, has high prevalence morbidity mortality, yet an understanding potential unifying mediators between these pathways that may improve clinical outcomes is largely unclear. IL-10 classically been designated immunosuppressive cytokine, although recent data suggest under certain conditions can be immune stimulatory. We sought to further investigate the effect on innate adaptive immunity in vitro human observational cohort...
Mazer, Monty B. MD; Bulut, Yonca Brodsky, Nina N. Lam, Fong W. Sturgill, Jamie L. PhD; Miles, Sydney M. BS; Shein, Steven Carroll, Christopher Remy, Kenneth E. MD, MHSc, MSCI; on behalf of the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network BLOODNET Immunology Section Author Information
We previously found that platelet-derived growth factor (PDGF) and 17beta-estradiol stimulate gonocyte proliferation in a dose-dependent, nonadditive manner. In the present study, we report gonocytes express RAF1, MAP2K1, MAPK1/3. Inhibition of RAF1 MAP2K1/2, but not phosphoinositide-3-kinase, blocked PDGF-induced proliferation. AG-370, an inhibitor PDGF receptor kinase activity, suppressed only also induced by 17beta-estradiol. addition, MAP2K1/2 inhibitors 17beta-estradiol-activated The...
Abstract Sepsis initiates simultaneous pro- and anti-inflammatory processes, the pattern intensity of which vary over time. The inability to evaluate immune status patients with sepsis in a rapid quantifiable manner has undoubtedly been major reason for failure many therapeutic trials. Although there considerable effort immunophenotype septic patients, these methods have often not accurately assessed functional state host immunity, lack dynamic range, are more reflective molecular processes...
Both severe SARS-CoV-2 infections and bacterial sepsis exhibit an immunological dyscrasia propensity for secondary infections. The nature of the dyscrasias these differing etiologies their time course remain unclear. In this study, thirty hospitalized patients with infection were compared ten critically ill over 21 days, as well healthy control subjects. Blood was sampled between days 1 after admission targeted plasma biomarker analysis, cellular phenotyping, leukocyte functional analysis...
A nonimmunocompromised patient developed life-threatening soft tissue infection with Trichosporon asahii, Fusarium, and Saksenaea that progressed despite maximum antifungal therapies aggressive debridement. Interleukin-7 immunotherapy resulted in clinical improvement, fungal clearance, reversal of lymphopenia, improved T-cell function. Immunoadjuvant to boost host immunity may be efficacious infections.
Background: The inability to evaluate host immunity in a rapid quantitative manner patients with sepsis has severely hampered development of novel immune therapies. enzyme-linked immunospot (ELISpot) assay is functional bioassay that measures the number cytokine-secreting cells and relative amount cytokine produced at single-cell level. A key advantage ELISpot its excellent dynamic range enabling more precise quantifiable assessment immunity. Herein, we tested hypothesis can detect changes...
Sepsis-induced immunosuppression involves both innate and adaptive immunity is associated with the increased expression of checkpoint inhibitors, such as programmed cell-death protein 1 (PD-1). The PD-1 poor outcomes in septic patients, models sepsis, blocking or its ligands antibodies survival alleviated immune suppression. While inhibitory are effective, they can lead to immune-related adverse events (irAEs), part due continual blockade pathway, resulting hyperactivation response....
Immunotherapy treatment for coronavirus disease 2019 combined with antiviral therapy and supportive care remains under intense investigation. However, the capacity to distinguish patients who would benefit from immunosuppressive or immune stimulatory therapies insufficient. Here, we present a patient severe defective response, treated successfully interleukin-7 on compassionate basis resultant improved adaptive function.A previously healthy 43-year-old male developed acute respiratory...
BACKGROUND. Sepsis remains a major clinical challenge for which successful treatment requires greater precision in identifying patients at increased risk of adverse outcomes requiring different therapeutic approaches. Predicting and immunological endotyping septic has generally relied on using blood protein or mRNA biomarkers, static cell phenotyping. Here, we sought to determine whether functional immune responsiveness would yield improved precision.
Summary Background The hygiene hypothesis states that early exposure to bacterial products such as lipopolysaccharide (LPS) may be protective against the development of allergic diseases. Whether atopic disease affects ability immune cells respond LPS is unclear. Our laboratory has demonstrated previously children express high levels Toll‐like receptor (TLR)‐4 on CD4 + in nasal mucosa. Objective To determine if with a history have impaired responses circulating leucocytes. Methods Peripheral...
Secreted proteins mediate essential physiological processes. With conventional assays, it is challenging to map the spatial distribution of secreted by single cells, study cell-to-cell heterogeneity in secretion, or detect low abundance incipient secretion. Here, we introduce "FluoroDOT assay," which uses an ultrabright nanoparticle plasmonic-fluor that enables high-resolution imaging protein We find plasmonic-fluors are 16,000-fold brighter, with nearly 30-fold higher signal-to-noise...
Sepsis remains a major clinical challenge for which successful treatment requires greater precision in identifying patients at increased risk of adverse outcomes requiring different therapeutic approaches. Predicting and immunological endotyping septic has generally relied on using blood protein or mRNA biomarkers, static cell phenotyping. Here, we sought to determine whether functional immune responsiveness would yield improved precision.
The global COVID-19 pandemic has claimed the lives of more than 750,000 US citizens. Dysregulation immune system underlies pathogenesis COVID-19, with inflammation mediated tissue injury to lung in setting suppressed systemic function. To define molecular mechanisms dysfunction we utilized a systems immunology approach centered on circulating leukocyte phosphoproteome measured by mass cytometry. We find that although is associated wholesale activation broad set signaling pathways across...