1.1 P38 Signaling Pathway

The inflammatory response plays a crucial role in the occurrence and development of numerous diseases. The interaction between inflammation and cancer is an important aspect of cancer occurrence. Therefore, the study of the mechanism of inflammatory response is the first step in the treatment of many diseases. During the transmission of inflammatory signals, the p38 signaling pathway plays a significant role.It is highly conserved in evolution and its regulation is closely related to Alzheimer's disease, cardiomyocyte hypertrophy, rheumatoid arthritis, and chronic enteritis, and it is involved in the regulation of cell growth, differentiation, aging, and death, influencing the occurrence and development of cancer. p38 is an important drug research target, and its inhibitors have great potential for clinical treatment.

As one of the discoverers of the p38 signaling pathway (1994, Science), Professor Han Jiahui led his laboratory to gradually analyze the core part of the p38 signaling pathway. His laboratory has always been at the forefront of this field internationally. Since 1993, it has published over 100 papers related to p38, the most among the same field worldwide.

The research on the mechanism of cell death has always been a very popular research direction. For a long time, cell necrosis was regarded as a passive and unregulated mode of death.

In 2009, Professor Han Jiahui and other laboratories independently identified that protein kinase RIP3 could convert tumor necrosis factor-induced cell apoptosis into cell necrosis. Cell necrosis was then gradually confirmed to be an active and regulated form of death (2009, Science), and was named "programmed cell necrosis". Subsequently, Professor Han Jiahui conducted in-depth and systematic research on the regulatory mechanisms and pathological physiological significance of programmed cell death, revealing several important regulatory links and proving that programmed necrosis plays an important role in the development of atherosclerotic lesions and in inhibiting viral replication (2011, Nat Immunol; 2013, Cell Res; 2013, Cell Rep; 2014, Cell Res; 2015, Nat Cell Biol; 2015, Cell Host Microbe).

Due to the significant role of programmed cell necrosis in the pathological process, key molecules such as RIP3 that mediate programmed cell necrosis have attracted increasing attention and have become important targets for potential drug development.

The immune system is the defense system that sustains human life. Immune cells are the key weapons for the body to eliminate pathogenic bacteria. When pathogenic bacteria invade immune cells, it causes inflammatory necrosis of the cells - pyroptosis. Pyroptosis is mediated by inflammatory proteases and is an important immune defense response of the body. It plays a significant role in eliminating pathogen infections and endogenous danger signals in the body. Recently, Professor Han Jiahui used quantitative mass spectrometry technology (2015, Nat Methods) to analyze the NLRP3 immune co-precipitation complex and identified another key component protein in the inflammasome, Gasdermin D (2015, Cell Res), which enhanced our understanding of the immune system's defense mechanism during pathogen infection. This achievement, along with other independent works published by other laboratories, was jointly selected as one of the "Top Ten Advances in Life Sciences in China" in 2015.

In addition to conducting more in-depth research on the mechanisms and physiological pathological significance of our pioneering and continuous work, our research group does not limit itself to the existing projects. Instead, it is still exploring new fields and striving to achieve more original and pioneering achievements.