MOLECULAR IMMUNOLOGY LABORATORY
CASPASE-11 NON-CANONICAL INFLAMMASOME
- INFLAMMATORY RESPONSES & DISEASES
1. Main Questions
● Role of caspase-11 non-canonical inflammasome in macrophage-mediated inflammatory response
● ID & VD of key molecules in this event
2. Key Rationales
● Inflammatory response consists of two major steps;
1. Priming: Preparatory step
2. Triggering: Activation & boosting step
● Cardinal feature of triggering step is activation of inflammasome, an intracellular protein complex composing of a pattern recognition receptor (PRR) and inflammatory molecules
● Canonical inflammasomes, such as NLR family inflammasomes and AIM2 inflammasome have long been demonstrated to play pivotal roles in inflammatory responses and pathogenesis of inflammatory diseases
● Non-canonical inflammasomes, such as mouse caspase-11 and human caspase-4 were recently discovered and some evidence has been reported to play inflammatory roles
● Despite these reports, the molecular and cellular mechanisms by which non-canonical inflammasomes induce inflammatory responses in inflamed cells have been poorly understood
● In our Lab, we aim to unveil novel mechanisms of which non-canonical inflammasome-mediated inflammatory responses in macrophages
CASPASE-11 NON-CANONICAL INFLAMMASOME-TARGETING IMMUNOTHERAPY
1. Main Questions
● Promising & novel therapeutic strategy for inflammatory diseases by targeting caspase-11 non-canonical inflammasome
● Key mechanism of action (MoA) & proof of concept (PoC)
2. Key Rationales
● Most of anti-inflammation studies have been mainly focused on targeting a priming step of inflammatory responses
● Targeting a triggering step is a new paradigm for developing anti-inflammatory therapeutics
● ID & VD of key modulators in caspase-11 non-canonical inflammasome-mediated inflammatory responses
● ID of new less toxic & more effective anti-inflammatory drug candidates
● Testing these candidates against various inflammatory diseases using animal disease models
DEVELOPMENT OF NOVEL
ANTI-INFLAMMATORY THERAPEUTICS
1. Main Questions
● Novel anti-inflammatory therapeutics for pan-inflammatory diseases
● Superior than current anti-inflammatory drugs - less toxicity & better efficacy
2. Key Rationales
● The first approach to target caspase-11 non-canonical inflammasomes to prevent and treat inflammatory diseases
● New paradigm of anti-inflammatory therapeutics
● First-in-class as well as Best-in-class anti-inflammatory drug development