Innate Immunity (Guangxun MENG)
Inflammation is an important host response to various stimuli and conditions including infection and tissue injury. Controlled inflammatory response is considered beneficial, but it can be rather detrimental if dysregulated. Diseases such as cancer, auto-immune diseases and infectious diseases all involve uncontrolled inflammation. There are many different mediators of inflammation, a crucial member of which is IL-1β. The production of functional IL-1β needs NF-kB dependent transcription of pro-IL-1β, followed with cleavage by caspases such as caspase-1. The activation of caspase-1 relays on the assembly of a protein complex called inflammasome, which consists of pattern recognition receptor (PRR) such as NLRP3 or AIM2, adaptor protein ASC and pro-caspase-1. The goal of our lab is to understand the function of innate immunity especially inflammasome in inflammatory diseases and related mechanisms.
Our scientific objectives include:
(1)Regulatory mechanism of inflammasome activation
NLRP3 inflammasome can be activated by various stimuli, including Alum, silica, influenza virus, ATP, which indicates common regulatory molecules are likely involved in the process. We will search for these regulators and clarify mechanisms for their involvement in inflammasome activation.
(2)Function of inflammasome in the control of microbial infection
As an important component of innate immunity, inflammasome is important for anti-microbial infection. Studies showed NLRP3 inflammasome is essential in initiation of immune response against Influenza virus, Adenovirus, Candida albicanset. al.. We will further explore the function of NLRP3 inflamamsome in anti-viral and fungal infections.
(3)Function of NLRs in autoimmune diseases and cancer
Early studies show that NOD2 and NLRP3 are involved in the development of IBD and CRC. We will further explore the role of these NLRs in the development of these diseases and identify new regulatory strategy.
(4) Pharmacological regulation of inflammasome activity
Since inflammasome is involved in many physiological and pathological process, it is of great therapeutic value to identify drugs to regulate inflammasome. We will screen existing drugs and new compounds to regulate inflammasome function.
(5) Inflammasome based adjuvant development
Traditional vaccines are gradually replaced by new generation of vaccines. Better adjuvants are required for improving these new vaccines. We will screen and verify novel adjuvants base on our inflammasome study.