- Autophagy in Disease and Therapy
- Toxoplasma gondii Research Studies
- Viral gastroenteritis research and epidemiology
- Mosquito-borne diseases and control
- Viral Infections and Immunology Research
- Cytomegalovirus and herpesvirus research
- Immune cells in cancer
- Inflammasome and immune disorders
- Calcium signaling and nucleotide metabolism
- Autoimmune and Inflammatory Disorders Research
- Immunodeficiency and Autoimmune Disorders
- Adipose Tissue and Metabolism
- HIV Research and Treatment
- Cardiomyopathy and Myosin Studies
- Kawasaki Disease and Coronary Complications
- Immune responses and vaccinations
- Cellular transport and secretion
- Studies on Chitinases and Chitosanases
- Metabolism, Diabetes, and Cancer
- Adipokines, Inflammation, and Metabolic Diseases
- Infectious Encephalopathies and Encephalitis
- Long-Term Effects of COVID-19
- Tryptophan and brain disorders
- Polyomavirus and related diseases
- Immunotherapy and Immune Responses
Washington University in St. Louis
2014-2025
St. Louis Children's Hospital
2016-2022
Children’s Discovery Institute
2022
The University of Texas Southwestern Medical Center
2007-2011
Howard Hughes Medical Institute
2011
Czech Academy of Sciences, Institute of Microbiology
2008
The bacterial pathogen Vibrio parahaemolyticus utilizes a type III secretion system to cause death of host cells within hours infection. We report that cell is completely independent apoptosis and occurs by mechanism in which injection multiple effectors causes induction autophagy, rounding, the subsequent release cellular contents. Autophagy detected appearance lipidated light chain 3 (LC3) increases punctae vacuole formation. Electron microscopy reveals production early autophagic vesicles...
Macrophages activated with interferon-γ (IFN-γ) in combination other proinflammatory stimuli, such as lipopolysaccharide or tumor necrosis factor-α (TNF-α), respond transcriptional and cellular changes that enhance clearance of intracellular pathogens at the risk damaging tissues. IFN-γ effects must therefore be carefully balanced inhibitory mechanisms to prevent immunopathology. We performed a genome-wide CRISPR knockout screen macrophage cell line identify negative regulators responses....
Plasma membrane rupture by Ninjurin-1 (NINJ1) executes programmed cell death, releasing large cellular damage-associated molecular patterns (DAMPs). However, the regulation and selectivity of NINJ1-mediated DAMP release remain unexplored. Here, we uncover that murine norovirus (MNoV) strategically co-opts NINJ1 to selectively intracellular viral protein NS1, while plasma simultaneously bulk-releases various DAMPs. Host caspase-3 cleaves precursor NS1/2, leading NS1 secretion via an...
Viruses adapt and modulate cellular pathways to allow their replication in host cells. The catabolic pathway of macroautophagy, for simplicity referred as autophagy, is no exception. In this review, we discuss anti-viral functions both autophagy select components the machinery, how viruses have evaded them. Some use membrane remodeling ability machinery build compartments cytosol or efficiently egress from cells a non-lytic fashion. remodeled membranes can even be found viral particles...
Significance Sepsis is a multifactorial syndrome with increasing incidence and significant mortality. While previous work implicated tumor necrosis factor (TNF)-induced cell death in sepsis, role for interferon-gamma (IFNγ), which synergizes TNF to activate macrophages, incompletely understood. We demonstrate using genome-wide CRISPR/Cas9 screening that genes regulating the cytosolic degradative pathway of autophagy protect against IFNγ-induced death. This requires its receptor depends on...
Neonatal cardiogenic shock most commonly occurs due to critical congenital heart disease, sepsis, metabolic disorder or arrhythmias. In particular, enterovirus infections are common in the neonatal period, and patients can present with fulminant myocarditis. Early recognition is imperative its high morbidity mortality without prompt aggressive treatment. We successful treatment of enteroviral myocarditis a pair monochorionic diamniotic twins cardiopulmonary support, intravenous...
Abstract Lysosomal membrane permeabilization (LMP) and cathepsin release typifies lysosome-dependent cell death (LDCD). However, LMP occurs in most regulated programs suggesting LDCD is not an independent pathway, but conscripted to facilitate the final cellular demise by other routines. Previously, we demonstrated that Caenorhabditis elegans ( C. ) null for a cysteine protease inhibitor, srp-6 , undergo specific pathway characterized cathepsin-dependent cytoplasmic proteolysis. We...
Interferon-γ (IFNγ) is a critical mediator of cell-intrinsic immunity to intracellular pathogens. Understanding the complex cellular mechanisms supporting robust interferon-γ-induced host defenses could aid in developing new therapeutics treat infections. Here, we examined impact autophagy genes response. We demonstrate that within pathway including
The largest known outbreak of enterovirus D68 (EV-D68) infections occurred during 2014. goal our study is to characterize the illness severity and clinical presentation children infected with EV-D68 in comparison non-EV-D68-human rhinoviruses/enteroviruses (HRV/EV).Our a retrospective analysis level, charges length stay who presented St. Louis Children's Hospital from August 8, 2014 October 31, tested positive for non-EV-D68-HRV/EV-infected patients. Chart review was performed all...
ATG5: autophagy related 5; ATG7: 7; ATG14: 14; ATG16L1: 16-like 1 (S. cerevisiae); BECN1: beclin 1, related; CASP1: caspase 1; CASP4/CASP11: 4, apoptosis-related cysteine peptidase; CIM: conditionally immortalized macrophage; CLP: cecal ligation and puncture; CSS: cytokine storm syndrome; DC: dendritic cell; IFNG/IFNγ: interferon gamma; IFNGR1: gamma receptor ip: intraperitoneal; iv: intravenous; IL12/p70: interleukin 12, p70 heterodimer; IL18: Interleukin 18; ITGAX/CD11c: integrin alpha X;...