Dr.Zhang zhigang received his PhD from the Institute of Genetics and Developmental Biology, Chinese Academy of Sciences in 2003, then worked as a postdoctoral researcher at the Institute of Biochemistry, Faculty of Medicine, University of Cologne, Germany from 2003 to 2009.In October 2009, he joined Shanghai Cancer Institute as a talent introduction, and is currently the leader of the neurotransmitter and tumor microenvironment research group.

His researches has been supported by the National Natural Science Foundation of China for key projects, major research projects, general projects, the 12th Five-Year Plan Period, the National High Technology Research and Development Program (863 Program), the Shanghai Municipal Education Commission Research and Innovation Program, and the Shanghai Jiao Tong University Medical-Industrial Crossover Research Fund, etc. He has published more than 60 SCI papers as corresponding author in international journals such as Gastroenterology, Gut, Hepatology, Journal of Hepatology, Nature Communications, Clincal Cancer Research, Cancer Research, Oncogene, etc. He is the president of Matrix Biology Committee of Chinese Physiological Society. He is an outstanding leader of Shanghai, as well as an outstanding leader of Shanghai Health System. He has applied for 9 national invention patents, obtained 6 national patent authorizations and 1 international PCT patent authorization. He was awarded the second prize of Shanghai Medical Science and Technology as first author.

Topic title: The monoamine neurotransmitter serotonin in tumor progression

Abstract:

The monoamine neurotransmitters including serotonin, dopamine, histamine and norepinephrine play critical roles in tumor microenvironment (TME). Serotonin is a neuromodulator with neurotransmitter and neuroendocrine functions that contributes to tumorigenesis. However, the molecular mechanism is not clear yet. We found that the serotonin system is disrupted in the TME of pancreatic cancer, which is primarily characterized by increased levels of peripheral 5-HT synthetic enzyme TPH1 and decreased levels of 5-HT degradation enzyme MAOA during pancreatic cancer progression. These changes lead to the accumulation of 5-HT in the microenvironment, activating the serotonin receptor HTR2B and subsequently enhancing the glycolysis of pancreatic cancer cells. Ultimately, this promotes the growth of pancreatic cancer cells under conditions of metabolic stress. Apart from the canonical serotonin receptor signaling transduction pattern, 5-HT-involved post-translational serotonylation has recently been noted. We found that serotonin had effect on the extracellular matrix (ECM) crosslinking in pancreatic cancer tissue through serotonylation, thereby influencing ECM stiffness to promote tumor development. In addition, serotonylaiton can also affect the immune cell function. We found a GAPDH serotonylation system that promotes glycolytic metabolism and antitumor immune activity of CD8+ T cells. Adoptive transfer of TPH1-overexpressing chimeric antigen receptor T (CAR-T) cells induced a robust antitumor response. Our study elucidates the impact of 5-HT on the tumor microenvironment from three different perspectives, providing new strategies for tumor treatment.