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Peking University Center for Human Disease Genomics (PUCHG) was set up in 2000, when the former Beijing Medical University was merged into Peking University. The purpose of its foundation was to keep up with the biological development in the 21st century to help build Peking University into one of the best universities in the world. The focus of its research is laid on human disease related genes as well as functional genomics. Being open, innovative, practical, and dynamic, its aim is to be one of the first-class research institutions in the world.

PUCHG is affiliated to Peking University and acts as an independent research entity. Prof. Ma Dalong, Director of PUCHG, is a senior professor from the Department of Immunology as well as vice chairman of the School of Basic Medicine of Peking University Health Science Center. Prof. Ma is also a member of the biology and modern agriculture committee of the National "863" Program. His major specialization areas include molecular immunology and biological-engineering drugs. During the recent years, he has been engaged in research on human functional genomics, which has led to a series of achievements.
An academic committee and responsible specialist panel was set up in PUCHG to examine and supervise the projects' selection and progression. The president of the academic committee is Academician and Professor Han Qide.

There are nearly 60 fellows working in PUCHG, including research scientists, post doctors, Ph.D and master graduates, and visiting scholars. The laboratories, covering a total area of over 500 square meters, are equipped with state-of-the-art instruments such as ABI3100 and 7700 Genetic Analyzer, Capillary Electrophoresis Apparatus£¬Poly-peptide Synthesizer and etc. Experiments on molecular biology, protein chemistry, cell biology and immunology can all be carried out here. Some of the core facilities are already in use.
During the past two years, the PUCHG has launched 56 projects to research human functional genomics as well as disease genomics. The financial aid has exceeded six million yuan. A series of achievements of PUCHG have been obtained since its establishment. For example, cloning and functional studies have been conducted over 30 novel human genes, such as apoptosis related genes, novel cytokine genes, cardiac-vascular related genes, and tumor related genes, etc. More than 10 papers have been published abroad and a series of human gene patents have been applied for. Some disease-related genes or SNPs have been cloned and discovered, such as hyperlipemia, arteriosclerosis, hypertension drugs-sensitive gene, chronic obstructive lung disease, bronchial asthma, pregnancy induced hypertension, osteoporosis, noise induced deafness, the lone arterial fibrillation, gastric carcinoma, esophageal carcinoma, lung cancer, heptoma, acute leukemia, endometrial carcinoma, chronic family benign pemphigus, steroid resistant nephritic syndrome, genetic deafness, childhood absence epilepsy, family febrile convulsions, schizophrenia, Children's autism, hyperkinetic syndrome of childhood, Alzheimer Disease, peridental disease(alveolysis), mitochondrial myopathy(MELAS) and etc. With the cooperation of four affiliated hospitals, Pathology Department has built a tissue bank, which emphasizes clinical tumor samples, and collected a number of DNA samples. Tissue chip was also developed.

Main Research Interest

Human Disease Genomics

Cooperating with the clinical affiliated hospitals, PUCHG has collected blood and tissue samples of many important diseases. This center is trying to build a bank of disease related genes and normalized tissue samples, with its emphasis on SNP analysis, drug genomics and discovery of disease-related genes. These works provide a basis for the research on pathogenesis, diagnosis, therapy and susceptibility analysis of clinical diseases.


Human Functional Genomics
Utilizing Differential Display and bioinformatics techniques, PUCHG is trying to discover and study human functional genes, and establish high-throughput protein expression and of biological activities screening system.


Research and Development of Human Gene Products
The PUCHG is also interested in developing patented gene products as well as in basic research. These products include biological engineering drugs, gene diagnosis reagent, target of gene therapy, monoclonal antibody, novel target of drugs, reagents for biological research and etc. In this aspect, PUCHG will develop collaboration with other industrial, academic and financial institutions, home and abroad, trying to establish a "research¡údevelopment¡úresearch" beneficial cycle.


Major projects undertaken in this lab

National Natural Sciences Foundation of China:
1.Functional Studies of human leukemia apoptosis related gene, TFAR19 (1998-2001)
Chief Investigator: Ma Dalong
2. Cloning and Functional studies of a mouse novel cytokine, TEIF1 (2000-2003)
Chief Investigator: Han Wenling
3. Cloning and Functional studies of a human novel cytokine, CKLF-H1 (2000-2003)
Chief Investigator: Wang Lu
4. Gene Regulation Studies of a novel cytokine, CKLF1 (2001-2004)
Chief Investigator: Xu Mingxu

National High Tech Program ("863")
1. Gene engineering and biological activity of novel cytokine CKLF-RP1 in vitro and in vivo (2001-2005)
Chief Investigator:Wang Lu
2. Functional and application studies of human novel cytokine CKLF1 and its isoforms. (2001-2005)
Chief Investigator: Han Wenling

National "973" Program
Basic Studies on pathogenesis, therapy and diagnosis of cardiovascular disease --- Studies on intracellular transport of cardiovascular cells (2000-2005)
Chief Investigator: Ma Dalong
Beijing Municipal Science And Technology Commission Grand Project:
Discovery and study of human important functional protein (cooperated with The Chinese National Human Genome Center (2002-2005)
Chief Investigator: Ma Dalong

Major Achievements:

Cloning, expression and functional analysis of a novel apoptosis-related gene, TFAR19 (PDCD5)

Dr. Liu Hongtao et al had reported in BBRC (Liu HT et al., 1999) of cloning a novel apoptosis facilitated gene, TFAR19 (TF-1 cell apoptosis related gene 19). Homo sapiens Official Gene Symbol and Name (HGNC) have nominated TFAR19 as PDCD5 (programmed cell death 5). mRNA expression profile, subcellular localization and its biological activity have been thoroughly studied. TFAR19 recombinant protein has been expressed and purified from E.coli. Monoclonal antibody was also developed. By now, it has been successfully demonstrated that the amino acid sequence of PDCD5 is rather conserved among eukaryotic species and is widely expressed in both adult and tumoral tissues, while its mRNA expression level is lower in embryonic tissues than that that in normal adult tissues. TFAR19 translocates rapidly from the cytoplasm to the nucleus of cells undergoing apoptosis (Chen YY et al., 2001). Research on the mechanisms revealed that TFAR19 facilitated cell apoptosis by specifically binding to Caspase-3 and positively regulated its activity. Since 1999, there have been great achievements on research of TFAR19: almost 20 papers have been published, patented invention has been applied. Dr. Liu Hongtao's dissertation won the prize for Chinese Excellent Doctoral Dissertations in 2000, the first prize of Chinese Natural Science Prize. The following are some papers and patents related to TFAR19 (PDCD5):

1. Hongtao Liu, et al: TFAR19, a novel apoptosis-related gene cloned from human leukemia cell line TF-1, could enhance apoptosis of some tumor cells induced by growth factor withdrawal. Biochem Biophy Res Comm, 1999, 254:203-210

2. Yingyu Chen, Ronghua Sun, Wenling Han, Yingmei Zhang, Quansheng Song, Chunhui Di, Dalong Ma. Nuclear translocation of PDCD5 (TFAR19): an early signal for apoptosis? FEBS Letter. 2001, 509(27): 191-196

3. Dalong Ma, Hongtao Liu, Yugang Wang, Yingmei Zhang, Quansheng Song, Chunhui Di, Jian T ang, Guanghui Chen. A polypeptide facilitating cells apotosis. Chinese patented invention, Applying NO. 98101869.6; Opening NO. CN1218833A.

4.Yingmei Zhang, Xiuzhen Xu, Hongtao Liu, Quansheng Song, Dalong Ma. The apoptosis-accelerating effect of human recombinant TFAR19 protein on leukemia HL-60 cells. Chin J Immunol. Chin J Immunol, 2000, 16(1): 8-11

5.Huiping Li, Yuxia Shao, Wu Sun, Baoying Zhu, Tingzhen Jia. Effect of rhTFAR19 protein of cell apoptosis of 7721 liver cancer cells induced by hydroxy camptothecin. Journal of Beijing Medical University 2000, 32(5): 408

6. Yingyu Chen, Yingmei Zhang, Ronghua Sun, Quansheng Song, Chunhui Di, Dalong Ma. Preparation and identification of monoclonal antibody against human apoptosis-related protein TFAR19. Acta Acad Med Sin 2000, 22(6):502

7. Quansheng Song, Wenling Han, Hongtao Liu, Dalong Ma. The cDNA cloning and sequencing of a novel mouse apoptosis related gene TFAR19. J Beijing Med Univ 1999, 31(4):309-311

8. Zhimin Cao, Yingmei Zhang, Yingyu Chen, Dalong Ma. Site-directed mutagenesis of human TFAR19 and its expression, purification and functional analysis. J Beijing Med Univ 2000, 32(4): 306

9. Jianfeng Jiao, Guanying Chen, Mei Huang, Zengwei Guan, Shuang Shi, Yingmei Zhang, Dalong Ma. Effect of rhTFAR19 protein on cell cycle and apoptosis of MCF-7 induced by r-ray. Chin J Oncol. 2000; 22(2)

10. Li Li, Yingyu Chen, Rui Zheng, Dalong Ma, Debing Wang. Expressioon of TFAR19 in apoptotic process of Jurkat cells induced with warious methods. J Exp Hematol 2000; 8(2): 81-84.

11. Yingyu Chen, Ronghua Song, Wenling Han, Yingmei Zhang, Quansheng Song, Dalong Ma. Nuclear translocation of apoptosis-related protein TFAR19 in TF-1 cells undergoing apoptosis. Journal of Peking University (Health Sciences) 2001, 33(2): 97-100.

12. Ying Wang, Yingmei Zhang, Tian Yang, Zhou Zhou, Chunhui Di, Dalong Ma. Cloning and sequencing of a Drosophia cDNA homologous to programmed cell death5 (PDCD5) gene. Chin J Biochem Mol Biol 2001, 17(2): 142-147.

13. Guorui Ruan, Shanshan Chen, Yan Chang, Jiayu Fu, Hui Wang, Yanrong Liu, Yaqin Qin£¬Jinlan Li. Abnormal expression of a novel apoptosis facilitated molecular- TFAR19 in the bone marrow cells of chronic leukemia patoents. J Beijing Med Univ 2002 In press

14. Min Rui, Yingyu Chen, Yingmei Zhang, Dalong Ma. Transfer of anti-TFAR19 monoclonal antibody into HeLa cells by in situ electroporation can inhibit the apoptosis. Life Science, 2002, 71(15): 1771-1778 download

15. Huikai Tian, Tian Xia, Chunsun Jiang et al., TFAR19 enhances the opening of permeability transition pore in the mitochondrial membrane of mice liver. Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao (Shanghai). 2002, 34(3): 279-284

16. Xianting Li, Xiaoning Mo, Donglan Xia, Yanan Liu, Quansheng Song, Yingmei Zhang, Dalong Ma. Expression, purification and identification of deletants of human TF-1 cell apoptosis related gene (TFAR19) in E.coli. Chinese Journal of Biochemistry and molecular Biology 2002, 18(4): 411-415.

Cloning, expression and functional studies of human novel cytokine family, CKLF

In 2001, Dr. Han Wenling et al had reported of cloning a novel cytokine, CKLF1 (Chemokine-like factor 1, original named UCK-1£¬U937 derived chemokine-1) and its isoforms, CKLF2, 3, 4, of which CKLF2 is the largest isoform. CKLF1 is induced by PHA while inhibited by IL-10. CKLF1 is a potent chemoattratant for human leukocytes and can stimulate the inflammation and proliferation of murine skeletal muscle, plays important physical and pathological roles, especially in autoimmune inflammation. CKLF2 could stimulate proliferation of a variety of cells and is involved in myogensis of skeletal muscle. CKLF's unique structure makes it a novel cytokine family. So it is of significance to conduct the academic and applied studies on CKLFs. By now, almost 10 papers have been published, and international and domestic patented invention has been applied. Dr. Han Wenling's dissertation won the prize for Chinese Excellent Doctoral Dissertations in 2002. The following are some papers and patents related to CKLFs:

1£®Wenling Han, Yaxin Lou, Junmin Tang, Yingmei Zhang, Yingyu Chen, Ying Li, Weifeng Gu,Jiaqiang Huang, Liming Gui, Yan Tang, Feng Li, Quansheng Song, Chunhui Di, Lu Wang, Qun Shi, Ronghua Sun, Donglan Xia, Min Rui, Jian Tang, Dalong Ma et al: Molecular cloning and characterization of chemokine-like factor 1 (CKLF1), a novel human cytokine with unique structure and potential chemotactic activity. Biochem J. 2001, 357, 127-135 download

2. Dalong Ma, Wenling Han, Yingmei Zhang, Quansheng Song, Chuhui DI, Jiaqiang Huang, Jian Tang, Guanghui Chen. Chemokine-like factors having cell chemokinesis function and proliferation-stimulating activity. International Patent: PCT/CH00/00026; American Patent: 09/801,115; European Patent: EP0198P.

3. Nanshan Zhong, Yaxia, Tan, Dalong Ma, Wenling Han£¬Quansheng Song, Yingyu Chen. Application of CKLF-1 in organ injury. Chinese invention patent number: 01139963.5, 2002
4.Lu Wang, Dalong Ma, Wenling Han, Hui Fan, Yingmei Zhang, Quansheng Sog, Chunhui Di. Chemokine-like factors homolog 1A and its isoform 1B have hematopoiesis-stimulating and immune-regulating function Chinese Invention Patent Application Number:00121027.0, 2001

4. Wenling Han, Dalong Ma, Peiguo Ding. Chemokine-like factors superfamily molecules have skeletal muscle stimulating and immune regulation activity. Chinese Invention Patent Application Number: 02122266.5, 2002

5. Wenling Han, Donglan Xia, Yaxin Lou, Min Rui, Quansheng Song, Yingmei Zhang, Chunhui Di, Dalong Ma. (Poster). The stimulating effect of chemokine-like factors (CKLFs) on skeletal muscle cells. Cell. Biology. International. 2001, 25(10): 1053-1054 (Abstract).

6. Zhiwei Xu, Hongye Deng, Dalong Ma et al., Effect of human chemokine-like factor-1 expression in vivo on the development of systemic lupus erythematosus in BXSB mice. Chinese Journal Of Rheumatology.2001, 5(3): 162

7. Wenling Han, Min Rui, Yingmei Zhang, Yingyu Chen, Yingcheng Zhong, Chunhui Di, Quansheng Song, Dalong Ma. Stimulating effect of Chemokine-like factors (CKLF-1) on the growth of bone marrow cells. ACTA Academiae Medicinae Sinicae 2001, 23(2):119-122

8£®Donglan Xia, Yaxin Lou, Wenling Han, Xianting Li, Quansheng Song, Yingmei Zhang, Dalong Ma. Study of the enhancing effect of rCKLF1, 2 on the proliferation of myoblast cells. J of Cellular and Molecular Immunology 2002, 18(4): 313

9£®Donglan Xia, Xianting Li, Yaxin Lou, Wenling Han, Peiguo Ding, Yingmei Zhang, Chunhui Di, Quansheng Song, Dalong Ma: Overexpression of chemokine-like Factor 2 promotes the proliferation and differentiation of C2C12 skeletal muscle cells. Biochimica et Biophysica Acta-Mol Cell Res. 2002, 1591 (1-3) 163-173

10. Donglan Xia, Yingyu Chen, Han Wenling, Xianting Li, Quansheng Song, Yingmei Zhang, Dalong Ma Overexpression of human CKLF2 promotes proliferation and survival of BALB/C 3T3 mouse fibroblast cells. Chinese Journal of microbiology and Immunology, (In press, 2002)

11.Yaxin Lou, Donglan Xia, Wenling Han, Xianting Li, Ying Li, Min Rui, Peiguo Ding, Quansheng Song, Yingmei Zhang, Dalong Ma. Molecular cloning and characterization of rat chemokine-like factor 1 and 2, submitted to GENE