A5086293678- Inflammasome and immune disorders
- Peptidase Inhibition and Analysis
- Ubiquitin and proteasome pathways
- Advanced NMR Techniques and Applications
- Toxoplasma gondii Research Studies
- Electron Spin Resonance Studies
- Signaling Pathways in Disease
- Heme Oxygenase-1 and Carbon Monoxide
- Endoplasmic Reticulum Stress and Disease
- Photosynthetic Processes and Mechanisms
- Trace Elements in Health
- Immune Response and Inflammation
- Galectins and Cancer Biology
- Calcium signaling and nucleotide metabolism
- interferon and immune responses
- Adenosine and Purinergic Signaling
- Cancer Immunotherapy and Biomarkers
- Ion Channels and Receptors
- Advanced MRI Techniques and Applications
- Gout, Hyperuricemia, Uric Acid
- Biomarkers in Disease Mechanisms
Memorial Sloan Kettering Cancer Center
2016-2024
Tri-Institutional PhD Program in Chemical Biology
2016-2024
Cornell University
2022
Rockefeller University
2022
California State University, Fullerton
2014-2015
Intracellular pathogens and danger signals trigger the formation of inflammasomes, which activate inflammatory caspases induce pyroptosis. The anthrax lethal factor metalloprotease small-molecule DPP8/9 inhibitors both NLRP1B inflammasome, but molecular mechanism activation is unknown. In this study, we used genome-wide CRISPR-Cas9 knockout screens to identify genes required for NLRP1B-mediated We discovered that induces cell death via N-end rule proteasomal degradation pathway. Lethal...
Abstract Intracellular pathogenic structures or activities stimulate the formation of inflammasomes, which recruit and activate caspase-1 trigger an inflammatory form cell death called pyroptosis. The well-characterized mammalian inflammasome sensor proteins all detect one specific type signal, for example double-stranded DNA bacterial flagellin. Remarkably, NLRP1 was first protein discovered to inflammasome, but signal that detects has not yet been identified. is highly polymorphic, even...
NLRP1 and CARD8 are related pattern-recognition receptors (PRRs) that detect intracellular danger signals form inflammasomes. Both undergo autoproteolysis, generating N-terminal (NT) C-terminal (CT) fragments. The proteasome-mediated degradation of the NT releases CT from autoinhibition, but stimuli trigger have not been fully elucidated. Here, we show several distinct agents interfere with protein folding, including aminopeptidase inhibitors, chaperone inducers unfolded response, accelerate...
Inflammasomes are multiprotein complexes formed in response to pathogens. NLRP1 and CARD8 related proteins that form inflammasomes, but the pathogen-associated signal(s) molecular mechanisms controlling their activation have not been established. Inhibitors of serine dipeptidyl peptidases DPP8 DPP9 (DPP8/9) activate both CARD8. Interestingly, binds directly CARD8, this interaction may contribute inhibition NLRP1. Here, we use activity-based probes, reconstituted inflammasome assays, mass...
Several cytosolic pattern-recognition receptors (PRRs) form multiprotein complexes called canonical inflammasomes in response to intracellular danger signals. Canonical recruit and activate caspase-1 (CASP1), which turn cleaves activates inflammatory cytokines gasdermin D (GSDMD), inducing pyroptotic cell death. Inhibitors of the dipeptidyl peptidases DPP8 DPP9 (DPP8/9) both human NLRP1 CARD8 inflammasomes. have different N-terminal regions but similar C-terminal that undergo autoproteolysis...
CARD8 is a pattern-recognition receptor that forms caspase-1-activating inflammasome. undergoes constitutive autoproteolysis, generating an N-terminal (NT) fragment with disordered region and ZU5 domain C-terminal (CT) UPA CARD domains. Dipeptidyl peptidase 8 dipeptidyl 9 inhibitors, including Val-boroPro, accelerate the degradation of NT via poorly characterized proteasome-mediated pathway, thereby releasing inflammatory CT from autoinhibition. Here, we show core 20S proteasome, which...
NLRP1 and CARD8 are related sensors that form inflammasomes, but the danger signals they detect not fully established. These proteins undergo autoproteolysis, generating repressive N-terminal (NT) inflammatory C-terminal (CT) fragments. The proteasome-mediated degradation of NT releases CT from autoinhibition, is then sequestered in a complex with full-length sensor DPP9. Here, we show cytosolic peptide accumulation activates these inflammasomes. We found diverse array peptides accelerates...
Abstract Intracellular pathogens and danger signals trigger the formation of inflammasomes, which activate inflammatory caspases induce pyroptotic cell death. The anthrax lethal factor metalloprotease small molecule DPP8/9 inhibitors both Nlrp1b inflammasome, but molecular mechanism activation is not known. Here, we used genome-wide CRISPR/Cas9 knockout screens to identify genes required for Nlrp1b-mediated pyroptosis, discovered that induces death via N-end rule proteasomal degradation...
The intrinsically disordered protein (IDP) stathmin plays an important regulatory role in cytoskeletal maintenance through its helical binding to tubulin and microtubules. However, it lacks a stable fold the absence of partner. Although has been focus research over past two decades, solution-phase conformational dynamics this IDP are poorly understood. It reported that is purely monomeric solution bears short region persistent foldedness, which may act nucleate folding C-terminal direction....
CARD8 is a pattern-recognition receptor that forms caspase-1-activating inflammasome. undergoes autoproteolysis, generating an N-terminal (NT) fragment with disordered region and ZU5 domain C-terminal (CT) UPA CARD domains. DPP8 DPP9 (DPP8/9) inhibitors, including Val-boroPro (VbP), accelerate the degradation of NT via poorly characterized proteasome-mediated pathway, thereby releasing inflammatory CT from autoinhibition. Here, we show core 20S proteasome, which degrades misfolded proteins...