The Key Laboratory of Immune Microenvironment and Diseases was approved by the Ministry of Education in October 2008. It belongs to the field of life sciences and is mainly engaged in applied basic research.The laboratory is established relies on the Basic Medical College of Tianjin Medical University with a laboratory area of 4,300 m2.It is currently composed of five technical platforms: cell biology laboratory, molecular immunology laboratory, molecular biology laboratory, biochemistry laboratory and experimental animal center.
Professor Zhi Yao is the director of the laboratory. Professor Tao Cheng, director of the State Key Laboratory of Hematology, Union Medical University of Chinese Academy of Medical Sciences, is the chairman of the laboratory academic committee.The laboratory consists of a large group of outstanding professors and scholars, including Cheung Kong Scholars, 3 winners of the National Science Fund for Distinguished Young Scholars, 4 winners of the National Science Fund for Excellent Young Scholars, talents funded by the New Century National Hundred, Thousand and Ten Thousand Talent Project, talents funded by National Ten-thousand Talents Program，young scientists with outstanding achievement funded by Ministry of Health, New Century Talents funded by Ministry of Education, talents funded by Tianjin Thousand Talents plan. The laboratory has undertaken 12 major scientific and technological major projects of “Major New Drug Creation”, National Natural Science Foundation Major Research Project Integration Project, National Key Research and Development Program of Ministry of Science and Technology, Major Projects and Key Projects of Natural Science Foundation, etc., and published more than ten articles of IF>10 SCI paper.
Main research directions
The research direction of the laboratory mainly covers oncology, pathology and pathophysiology, molecular biology research, and closely focuses on the molecular immunological mechanism of the immune microenvironment and disease, the regulation mechanism of immune cell signal transduction pathway and infectious diseases.
One direction of the laboratory is the research on immune molecules and diseases and immune peptide drugs, including biological functions of small molecular substances in immune microenvironment; drug screening, related mechanism research and preclinical application research of small molecule polypeptides against tumor and immune related diseases; related genes and proteins with tumor metastasis, providing potential targets for immune peptides in the state of the immune microenvironment; the study on the biological characteristics of cancer stem cells and their relationship with the immune microenvironment; and research on biological treatment of cancer stem cells. The study of the immune microenvironment and its related molecules and of the pathogenesis of tumors will provide theoretical basis for biotherapy such as new therapies and new drugs.
One direction of the laboratory is the study on the mechanism of signal transduction pathway in immune microenvironment, including the mechanism study of SND1 protein promoting chromatin relaxation in DNA damage, and its relationship with the sensitivity of hepatocellular carcinoma by regulating the expression of lncRNA UCA1; explore the role of NRF2 oxidative stress clearance pathway in the development of autosomal dominant polycystic kidney disease ; and its molecular mechanism; and the molecular mechanisms study of Hippo-YAP regulating atherosclerosis and of exercise-regulated metabolism.
One direction of the laboratory is the research on molecular pathogenesis and drug resistance mechanism of pathogenic microorganisms, including the role of dendritic cells, NK cells and T cells in anti-infective immunity; bacterial pathogenic genes and its relationship with immune microenvironment; bacterial resistance genes and its relationship with their immune microenvironment; the pathogenicity of mycoplasma and its relationship with the immune microenvironment; and the study of fungal pathogenicity and its related drug targets.
Symbolicachievements
1. Research group ofProf. Zhi Yao is dedicated to the research of tumor microenvironment and innovative new drugs for tumors, and relationship between cytokines and diseases. To discover the immunological mechanism of tumorigenesis, the group has studied the relationship between cancer, prostate cancer and liver cancer and other tumors. The group has shown that USP52 is a deubiquitinating enzyme and it can regulate chromatin assembly by stabilizing ASF1A, which may be involved in the development of breast cancer. It is not only important for understanding the enzyme activity and function of USP52, but also helpful for understanding the epigenetic mechanism of breast cancer genomic instability. The research was published at Nature Communications in 2018. In addition, a new type of immune peptide supported by the National Science and Technology Major New Drug Creation Project is undergoing clinical trials, and it is expected to obtain a Class I anti-tumor drug certificate with independent intellectual property rights in China.
2. Research group ofProf. Zhe Liu found that Aiolos was expressed in a variety of solid tumor cells. The high expression of Aiolos indicates a short survival period of tumor patients; Aiolos can down-regulate the expression of a series of cell adhesion-related proteins and destroy intercellular junctions between tumor cells and adhesion between tumor cells and extracellular matrix and promote the release of tumor cells from the epidermal cell sheet structure, which ultimately promotes the distant metastasis of tumor cells. It is proposed that solid tumor cells can acquire certain characteristics of lymphocytes (such as anoikis resistance) through the co-opt lymphocyte transcriptional regulation pathway, and realize a new perspective of distant proliferation. This finding is expected to be a clinical diagnosis and treatment of solid tumors. The research was published in the cancer field authoritative journal Cancer Cell.
3. Research group of Prof. Jie Yang found that Tudor-SN protein interacts with TGFβ, and over-activation of TGFβ pathway leads to abnormally elevated Tudor-SN expression in breast cancer tissues. The TGFβ pathway induces an abnormal increase in Tudor-SN expression by the transcriptional activation of the Tudor-SN gene by its downstream transcription factor Smad3. The overexpressed Tudor-SN further induced the degradation of RhoA by increasing Smurf1 activity, resulting in disordered cytoskeleton arrangement of tumor cells and increased invasion and migration ability. The research was published in Cancer Research.
4. Research group ofProf. Lei Shiexplored the role and molecular mechanism of USP7 and MRN/MDC1 complexes in the development of cervical cancer, which provides a possible molecular target for the treatment of cervical cancer; and further suggested that The treatment of small molecule inhibitors targeting USP7 and radiotherapy and chemotherapy in cervical cancer patients with high expression of USP7 and MDC1, cervical cancer cells can be killed more effectively. The research was published in The Journal of Clinical Investigation.
