A5065657128- Inflammasome and immune disorders
- Immune Response and Inflammation
- interferon and immune responses
- NF-κB Signaling Pathways
- Influenza Virus Research Studies
- Respiratory viral infections research
- Helicobacter pylori-related gastroenterology studies
- COVID-19 Clinical Research Studies
- Cell death mechanisms and regulation
- Animal Disease Management and Epidemiology
- Osteomyelitis and Bone Disorders Research
- Heme Oxygenase-1 and Carbon Monoxide
- RNA Interference and Gene Delivery
- Genomics and Rare Diseases
- Animal Virus Infections Studies
- Kawasaki Disease and Coronary Complications
- Molecular Biology Techniques and Applications
- Immune Cell Function and Interaction
- Cancer-related molecular mechanisms research
- Mechanisms of cancer metastasis
- Multiple Myeloma Research and Treatments
- Chronic Kidney Disease and Diabetes
- Immunotherapy and Immune Responses
- IL-33, ST2, and ILC Pathways
- T-cell and B-cell Immunology
Sanofi (United States)
2025
St. Jude Children's Research Hospital
2019-2023
IGM Biosciences (United States)
2023
National Institute of Immunology
2015-2021
Cedars-Sinai Medical Center
2017-2021
Children's Research Hospital
2020
Lung Institute
2017-2018
Programmed cell death plays crucial roles in organismal development and host defense. Recent studies have highlighted mechanistic overlaps extensive, multifaceted crosstalk between pyroptosis, apoptosis, necroptosis, three programmed pathways traditionally considered autonomous. The growing body of evidence, conjunction with the identification molecules controlling concomitant activation all by pathological triggers, has led to concept PANoptosis. During PANoptosis, inflammatory occurs...
Interferon regulatory factor 1 (IRF1) regulates diverse biological functions, including modulation of cellular responses involved in tumorigenesis. Genetic mutations and altered IRF1 function are associated with several cancers. Although the immunobiology cancer is emerging, IRF1-specific mechanisms regulating tumorigenesis tissue homeostasis vivo not clear. Here, we found that mice lacking were hypersusceptible to colorectal functions both myeloid epithelial compartments confer protection...
Coronaviruses have caused several zoonotic infections in the past two decades, leading to significant morbidity and mortality globally. Balanced regulation of cell death inflammatory immune responses is essential promote protection against coronavirus infection; however, underlying mechanisms that control these processes remain be resolved. Here we demonstrate infection with murine mouse hepatitis virus (MHV) activated NLRP3 inflammasome form PANoptosis. Deleting components or downstream...
Candida albicans and Aspergillus fumigatus are dangerous fungal pathogens with high morbidity mortality, particularly in immunocompromised patients. Innate immune-mediated programmed cell death (pyroptosis, apoptosis, necroptosis) is an integral part of host defense against pathogens. Inflammasomes, which canonically formed upstream pyroptosis, have been characterized as key mediators sensing drivers proinflammatory responses. However, the specific pathways sensors activated context...
Abstract The NLRP3 inflammasome is activated in response to microbial and danger signals, resulting caspase-1–dependent secretion of the proinflammatory cytokines IL-1β IL-18. Canonical activation a two-step process requiring both priming signals. During activation, associates with mitochondria; however, role for this interaction unclear. In article, we show that mouse caspase-1 independently interact mitochondrial lipid cardiolipin, which externalized outer membrane at reactive oxygen...
Significance The canonical NF-κB pathway mediates controlled nuclear activation of RelA factors, which induce proinflammatory genes. Uncontrolled activity, however, fuels aberrant intestinal inflammation. What triggers pathological activity in the colitogenic gut remains unclear. noncanonical module typically directs immune organogenesis involving Nfkb2 gene products. We find that this otherwise harmless signaling amplifies inflamed colon inflammatory bowel disease patients and mice,...
Tissue microenvironment functions as an important determinant of the inflammatory response elicited by resident cells. Yet, underlying molecular mechanisms remain obscure. Our systems-level analyses identified a duration code that instructs stimulus specific crosstalk between TLR4-activated canonical NF-κB pathway and lymphotoxin-β receptor (LTβR) induced non-canonical signaling. Indeed, LTβR costimulation synergistically enhanced late RelA/NF-κB to TLR4 prolonging target gene-expressions....
Environmental drug resistance constitutes a serious impediment for therapeutic intervention in multiple myeloma. Tumor-promoting cytokines, such as tumor necrosis factor (TNF), induce nuclear factor-κB (NFκB)- driven expression of pro-survival factors, which confer myeloma cells to apoptotic insults from TNF-related apoptosis-inducing ligand (TRAIL) and other chemotherapeutic drugs. It is thought that RelA:p50 dimer, activated IκBα-inhibited complex response TNF-induced canonical NFκB...
Background: Although mRNA vaccines have the potential to be developed and deployed rapidly combat infectious diseases, ideal method of administration boosting schedule strategy for generating optimal immunogenicity is an area active research. We compared immune responses resulting from different schedules prime–boost either ipsilaterally or contralaterally in relation initial vaccine dose. Methods: Influenza hemagglutinin (HA) was used as a model antigen vaccination regimens mice using both...
The COVID-19 pandemic has caused significant morbidity and mortality. Currently, there is a critical shortage of proven treatment options an urgent need to understand the pathogenesis multi-organ failure lung damage. Cytokine storm associated with severe inflammation organ damage during COVID-19. However, detailed molecular pathway defining this cytokine lacking, gaining mechanistic understanding how SARS-CoV-2 elicits hyperactive inflammatory response develop effective therapeutics. Of...
Abstract Exaggerated inflammatory responses during influenza A virus (IAV) infection are typically associated with severe disease. Neutrophils among the immune cells that can drive this excessive and detrimental inflammation. In moderation, however, neutrophils necessary for optimal viral control. study, we explore role of nucleotide-binding domain leucine-rich repeat containing receptor family member Nlrp12 in modulating neutrophilic lethal IAV infection. Nlrp12−/− mice protected from...
Abstract Inflammasomes are intracellular signaling complexes that assembled in response to a variety of pathogenic or physiologic stimuli initiate inflammatory responses. Ubiquitously present LPS Gram-negative bacteria induces NLRP3 inflammasome activation requires caspase-11. We have recently demonstrated IFN regulatory factor (IRF) 8 was dispensable for caspase-11–mediated during transfection; however, its role bacteria–mediated remains unknown. In this study, we found IRF8 promotes murine...
During influenza virus entry, the hemagglutinin (HA) protein binds receptors and causes membrane fusion after endosomal acid activation. To improve vaccine efficiency pandemic risk assessment for currently-dominant H3N2 viruses, we investigated HA stability of 6 reference viruses 42 circulating viruses. Recent had destabilized proteins due to egg-adaptive mutation HA1-L194P. Virus growth in cell culture was independent stability. In ferrets, required a relatively stable (activation...
Understanding how animal influenza A viruses (IAVs) acquire airborne transmissibility in humans and ferrets is needed to prepare for respond pandemics. Here, we investigated the replication transmission of swine H1N1 isolates P4 G15, whose majority population had decreased polymerase activity poor hemagglutinin (HA) stability, respectively. For both isolates, a minor variant was selected transmitted ferrets. Polymerase-enhancing PA-S321 airborne-transmitted propagated one ferret....
Macrophage-specific insulation of canonical NF-κB signaling from the noncanonical pathway prevents excessive inflammation.
Noncanonical inflammasome activation by cytosolic lipopolysaccharide (LPS) is a critical component of the host response to Gram-negative bacteria. Cytosolic LPS recognition in macrophages preceded Toll-like receptor (TLR) priming signal required induce transcription components and facilitate metabolic reprograming that fuels inflammatory response. Using genome-scale arrayed siRNA screen find regulators mouse macrophages, we identified mitochondrial enzyme nucleoside diphosphate kinase D...
Chronic recurrent multifocal osteomyelitis (CRMO) in humans can be modeled Pstpip2cmo mice, which carry a missense mutation the proline–serine–threonine phosphatase–interacting protein 2 (Pstpip2) gene. As cmo disease experimental model analogous to human CRMO, is mediated specifically by IL-1β and not IL-1α, delineating molecular pathways contributing pathogenic production crucial developing targeted therapies. In particular, our earlier findings support redundant roles of NLR family pyrin...
ABSTRACT Transient albuminuria induced by pathogen-associated molecular patterns (PAMPs) in mice through engagement of Toll-like receptors (TLRs) is widely studied as a partial model for some forms human nephrotic syndrome (NS). In addition to TLRs, CD80 has been shown be essential PAMP-mediated albuminuria. However, the mechanistic relationships between and remain unclear. Here, we show that CD80-uria many TLR ligands are dependent on expression TLRs their downstream signalling intermediate...
Abstract Exaggerated inflammatory responses during influenza A virus (IAV) infection are typically associated with severe disease. Neutrophils among the immune cells that can drive this excessive and detrimental inflammation. In moderation, however, neutrophils necessary for optimal viral control. study, we explore role of nucleotide-binding domain leucinerich repeat containing receptor (NLR) family member Nlrp12 in modulating neutrophilic lethal IAV infection. Nlrp12−/− mice protected from...