National Laboratory of Oncogenes and Related Genes
(Shanghai Jiao Tong University Cancer Institute)

National Laboratory of Oncogenes and Related Genes, located in Shanghai Cancer Institute, was approved in 1985 by the State Planning Committee, and established in 1987.

Professor Sheng-Li Yang of Shanghai Cancer Institute, an academician of Chinese Academy of Engineering is the present director of the lab. Professor Jian-Ren Gu, an academician of CAE too, is the chairman of the Lab Academic Committee, comprising famous scientists specializing in molecular biology, genetics, and cell biology. At present, the laboratory has total 33 staffs, including 13 researchers (7 seniors), 19 technicians and 1 research assistant.

Research has been focused on human functional genomics, searching for and identifying new genes related to liver cancer (i.e. oncogenes, tumor suppressor genes, apoptotic genes, growth factors and their receptors, DNA repair genes, and other potentially therapeutic genes), and elucidating the molecular mechanism of carcinogenesis, especially in hepatocellular carcinoma. On the other aspect, the laboratory has emphasized the basic research on cancer gene therapy to explore novel nonviral efficient and targeting gene transfer systems and controllable expression of therapeutic genes transduced into human cells for gene therapy.

1. In the middle of 1980's, based on identifying more than 7 oncogenes or related genes involved in human primary hepatocellular carcinoma, a concept was addressed that each type of human cancer should have its spectrum or profile of activated protooncogenes and defective tumor suppressor genes. The researchers won both the Award of National Science and Technology Progress (Grade II) and the Award of Medical Science and Technology Progress by the Ministry of Public Health (Grade I). The above concept of cancer-related or specific profile of activated or inactivated genes holds true in the present genomics era. The researchers were also honored with the Award of Medical Science and Technology Progress (Grade II) for their construction and application of cDNA libraries from human embryonic and fetal tissues.

2. Discovery for the first time of genomic abnormality on human chromosome 17p13.3 in liver cancer. This aberration appears to present ubiquitously in liver cancer samples form different areas in the country. The results suggest that the short arm of chromosome 17 must contain some unknown important oncogenes and tumor suppressor genes involved in hepatocarcinoma development. This finding published on Carcinogenesis of 1993 has been intensively noticed and frequently referred to by international colleagues announced by Science 1993; to be one of the Chinese scientists’ papers cited most frequently. Since then, large scale sequencing was performed and 13 novel genes were identified. The high score LOH at this loci was further confirmed by genome-wide genotyping and CGH. One of these candidate genes C63R was proved to possess tumor-suppressing activity (Cancer Res. 2002). In addition, expression profile of liver cancer was analyzed, in collaborating with the South Center of Shanghai Genomic Res. (PNAS, USA, 2002).

3. A high through-put functional screening of genes based on cell growth has been accomplished. Out of 3x104 clones, more than 300 novel full-length cDNA clones have been isolated, with a function of either stimulating or inhibiting cell growth. All of them have been filed for China Patent, 4 of them were registered in PCT. Several cDNA clones have been characterized as prime important genes in cancer, such as LASS-2 and its partner V-ATPase, playing essential function in cancer growth or invasion.

4. Study on gene therapy of human brain malignant glioblastoma with TK gene isolated from Chinese Herpes simplex virus I. The study has been resulted in the Phase I clinical trial approved by the Ministry of Public Health in 1996, the first clinical trial of cancer treatment by means of gene therapy in China, the protocols of which have been patented.

5. Construction of a novel nonviral receptor-mediated targeting delivery system was accomplished for gene therapy. In vivo experiments with laboratory animals indicated that these novel delivery systems can target therapeutic genes to cancers of liver, stomach, lung and ovary. The nonviral gene delivery system was awarded of patent both from China and US.

The Laboratory is equipped with phosphor Image, Silicon graphics work station, nucleic acid and protein image analysis system, automatic DNA sequencer, DNA synthesizer, peptide synthesizer and electron-microscope, etc. These equipments provide the essential facilities for research in molecular and cell biology of cancer.

The laboratory follows the policy carrying out extensive collaboration in research projects with institutions such as Hong Kong University Medical School, Hong Kong Science and Technology University and more than 10 domestic universities. International collaboration includes National Cancer Institute (U.S.), Toronto University (Canada), Pusan University (Korea), and etc.