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International Joint Laboratory of Nucleoprotein Gene Regulation in Henan Province

2018年05月29日    views

Ⅰ. Brief Introduction

As a provincial key laboratory, International Joint Laboratory of Nucleoprotein Gene Regulation in Henan province was built and approved by Provincial Science& Technology Department in Dec, 2017. It was firstly rooted in the discipline of preclinical medicine in School of Basic Medical Sciences of Henan University, later it also has joined the relevant clinical departments of School of Pharmacy of Henan University, School of Nursing of Henan University, School of Life Sciences and three affiliated hospitals of Henan University. Through years of genuine collaboration and communication, cooperation has been reached. By now, the PCNP scientific research collaboration group hasbeen established based on common interest, which is gradually integrated and developed rapidly. It was initially as the medical molecular biology laboratory in School of Basic Medical Sciences, which was founded in 2001. With the belief of co-construction, sharing, and win-win, it achieved steady development and growth after years of sincere cooperation with domestic and foreign counterparts, which includes Japan, Canada and some American universities like Columbia University, Emory University, University of Kansas, University of Kentucky, New York City College. The laboratory was successively approved by the signal transduction laboratory in Henan University (2015), the pulmonary hematopoiesis and respiratory diseases laboratories (2017) and the signal transduction laboratory in Kaifeng city (2018).The laboratory has instrumentation of worth than 13 million RMB, covering an area of 1,500 square meters, with 49 main members, including 13 key members of returnees, 40 full-time employees, and 9 overseas part-time employees. With 10 research groups, they carry out joint research on PCNP (PEST-containing nuclear protein) functions around the research fields of vascular immunity, muscular immunity, tumor immunity and neuro immunity. Among all members of this laboratory, there are 7 distinguished professors of Yellow River scholars, 36 with doctoral degree which accounts for 70%. There are more than 50 graduated graduate students and 49 graduate students, including 3 foreign doctoral students and several postdoctoral students. Currently, theChairman of Academic Committee of Laboratory, Professor HUANG Canhua, also entitled as Chief Scientist for National 973 Program, Chang Jiang Scholars Program Endowed Professor and the winner of National Science Fund for Distinguished Young Scholars. He is also the dean of West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University.

Laboratory Director: JI Xinying.

Executive Deputy Director: DUAN Shaofeng.

Deputy Director& Director: WU Dongdong.

Director of the U.S.: John M Tarbell.

Deputy Director of the U.S.: SUN Shiyong

Ⅱ. Dominant Advantages and Unique Features

Dominant Advantages in the Research Field of Nucleoprotein PCNP:

1. We have been continuously exploring nucleoproteinPCNP for 17 years, and achieved preliminary achievements.

2. The world's first PCNP knockout mice were successfully bred and functional studies are underway.

3. The inhibitory effect of PCNP on neuroblastoma was first discovered in nude mice models and its research paper also was published online by BMC Cancer in May, 2018, which is the first paper in this field.

4. One national invention patent related to PCNP has been declared.

5. The molecular mechanism of diaphragmatic muscle weakness after infection (sepsis) is unique and domestically leading. Four programs have been approved under the National Natural Science Foundation of China in the field of muscle weakness.

6. There are 22 Chinese and English literatures on PCNP all over the world and 14 of them are from our laboratory.

These results have contributed the international leading position to the laboratory in the field of nucleoprotein PCNP research.

Ⅲ.Research Fields and Directions

The research focusingon our laboratory is mainly the molecular mechanism of nucleoprotein pathogenesis and the development of related drugs.There are two main research directions:

(1) PCNP and Muscle Injury Protection:

It aims to confirm that PCNP can effectively ameliorate diaphragmatic weakness after infection. The study group has been working on diaphragm dysfunction after infection for many years especially on its relationship and nucleoprotein PNCP (PEST proteolytic signal containing nuclear protein). It also made an in-depth study of the mechanism of hydrogen sulfide (H2S) on sepsis-induced diaphragmatic dysfunction. And it was found that exogenous H2S could attenuate the apoptosis and inflammatory response of muscle cells through ROS/MAPK and TLR4/NF-κBsignaling pathway, thus improving the diaphragmatic dysfunction induced by bacterial endotoxin in rats. The significance of this work lies in the discovery of that H2S that can protect the diaphragm function after infection and reduce the damage of diaphragm cells, which will provide new targets, new ways and new thinking for clinical treatment of diaphragm dysfunction. It may bring the hope of rapid recovery to many patients in intensive care units.

The research paper entitled as “Hydrogen Sulfide Alleviates Lipopolysaccharide-induced Diaphragm Dysfunction in Rats by Reducing Apoptosis and Inflammation Through ROS/MAPK and TLR4/NF-kB Signaling Pathways” has been published by SCI Journals named “Oxidative Medicine and Cellular Longevity”(JCR2). The research was supported by three general programs of the National Natural Science Foundation of China and one joint program, meanwhile one more National Natural Science Foundation program was applied in 2018.

Up-regulation of PCNP based on protein 4.1R inhibition can improve myasthenia gravies symptoms, providing new ideas for understanding the pathogenesis of autoimmune diseases and finding new treatment methods.

(2) PCNP and Tumor Suppression:

PCNP may have a tumor suppressive effect similar to P53, and it has a very significant inhibitory effect on nude rat neuroblastoma, with the inhibitory rate reaching 37.7%-79.7%.

The research on nucleoprotein PCNP was carried out earlier in the world. While working in the United States, Dr. JI Xinying had observed the high expression of the gene in the immune system and he continued to study the function of the gene after returning to China. As a nucleoprotein containing PEST sequence, PCNP (PEST-containing Nuclear Protein) mainly exists in the nucleus.It is a substrate of protein ligase NIRF with ubiquitination ability, through which it is ubiquitinated and thus involved in the regulation of cell cycle.The specific molecular mechanism is unclear and its relationship with tumors has not been reported. Recently, the research team found that PCNP has a tumor suppressive effect on human neuroblastoma, especially in the tumor formation experiment of nude mice.The tumor suppressive effect of PCNP is significant, and the inhibition rate is up to 79.7%, with an average of 60.8%. If this result can be further clinically verified, it will provide a new target and idea for the treatment of human neuroblastoma and other tumors.

On April 18, 2018, the paper of our research group named "Pest Containing Nuclear Protein Mediates the Proliferation, Migration, and Invasion of Human NeuroblastomaCells through MAPK and PI3K/AKT/mTORPathways" was officially accepted by BMC Cancer, a well-known journal in the field of Cancer research, and published online on May 2.It indicates that this research result has been internationally recognized, and it is the first paper in the field of PCNP gene function research and one of few papers on PCNP, which confirms the role and mechanism of PCNP in tumor inhibition and opens up a new research field.


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