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State Key Laboratory of Medical Genomics

Brief Introduction

The Lab's precursor is the Key Laboratory for Human Genome Research co-sponsored by Shanghai Municipal Government, the Ministry of Health and the Ministry of Education. During the past several years, an abundance of innovative achievements was made. In terms of the research on leukemia-related genomics, with acute promyelocytic leukemia (APL) as the model, the researchers of the Lab systematically and profoundly elucidated the critical role of the fusion genes resulted from chromosomal translocation and their protein products in the pathogenesis of APL. In addition, they successfully applied differentiation and apoptosis induction therapy to treat APL with all-trans retinoic acid and arsenic trioxide. They were the first to locate the related loci of the primary hypertension and the type II diabetes among Chinese population and for the first time in the world launched large-scale gene expression analysis of CD34+ hemotopoietic stem/progenitor cells and hypothalamus-pituitary-adrenal axis, two systems of great medical significance. The achievements mentioned above enjoy an appreciation by the international scientific community. Especially, the innovative clinical therapy based on the study of APL genomics has been widely applied in the world.State Key Laboratory of Medical Genomics


Members

  • Director
  • Chen Sai-Juan

  • Director of Academic Committee
  • Chen Zhu

  • Team Members
  • Ji Zhang, Zhu-Gang Wang, Ding-Liang Zhu, Guang Nin, Xiao-Ying Li, Xiang-yin Kong, Xiao-Dong Xi, Ting-Xi Liu, Jiang Zhu, Jiong Hu, Wei-Li Zhao, Jian-Hua Tong, Huai-Dong Song, Kan-Kan Wang, Qiu-Hua Huang, Guo-Yu Meng, Xiao-Wei Zhang.


    Research Fields

    The research orientations of the Lab centers include solving the key scientific problems in life and medical sciences, and integrating the latest scientific achievements of genomics into the medical practice. Over the past five years, a series of technological platforms of genomics including large-scale genomic sequencing and genotyping, DNA sequence mutation detection, biochips for transcriptome, metabolomics and proteome analysis, large-scale transgenics and gene knockout model organisms and bioinformatics were implemented. Epigenetics with modifications including DNA methylation,histone methylation and acetylation as the core and the malignant cancers such as leukemia and other human diseases with high prevalence in China such as primary hypertension and type II diabetes as the objects for study, the Lab is focusing on the localization and identification of disease-related genes and the characterization of the regulatory pathways and network of their protein products. Meanwhile, the Lab has been developing molecular mechanism-based new methods of disease prevention, diagnosis and treatment, in order to improve health and advance the nation's capability of prevention and cure of diseases.


    Research Achievements

  • The Lab was the first in the world to treat acute promyelocytic leukemia (APL) with all-trans retinoic acid (ATRA) and proved for the first time in clinic that cancer cells were reversible. Recently the Lab innovatively treated newly diagnosed APL patients with combined therapy of ATRA and arsenic trioxide (As2O3). Seven-year follow-up showed 5-yr relapse-free survival (RFS) could be as high as 95%. APL has been rendered into the first curable subtype of acute myeloid leukemia from the previously most malignant leukemia. What's more, modern biochemical methods were used to analyze the collaborative treatment mechanisms of different ingredients in tablet of berberine (Realgar as the main ingredient and Natural Indigo and Salvia Miltiorrhiza as the auxiliary) and  rationales and molecular mechanisms of the compatibility of "Jun", "Chen", "Zuo" and "Shi" in Realgar-Indigo Naturalis Formula was elucidated in TCM, promoting and also providing a paradigm for the internationalization of TCM and convergence of Eastern and Western medicine. Presently the concept of target therapy of APL is being extended to other types of leukemia.
  • State Key Laboratory of Medical Genomics

  • Study on the leukemia pathogenesis
  • New genetic mechanisms for chronic malignant transformation of myeloid leukemia were discovered. Through gene screening on 85 cases of CML patients with blast transformation, 10% cases were identified to get GATA-2 mutation, which is one of the most important genetic mechanisms of malignant transformation of CML. The Lab also elucidated the mechanisms of C-KIT mutation/over expression in t(8;21) AML, enriching the theory of stepwise leukemogenesis. What's more, the Lab explored the role of NOTCH1 mutation and some oncogenic fusion gene products such as NUP98-IQCG and FIP1L1-PDGFRa

  • Set up normal hematopoietic stem/progenitor cells gene expression profile
  • The lab discovered and proved that retinoic induced gene-I (RIG-I) is a negative regulatory factors of myeloid hematopoiesis. The studies of development epigenetic control led to a better understanding of embryonic erythropoiesis and may constitute a novel therapeutic target for improving the clinical outcome of patients with thalassemia.

  • Human Disease Genomics
  • The Lab also got important findings in the identification of detection of susceptible genes in mono and polygenic diseases such as cataracts, congenital nystagmus, and found out they are caused by Hsf4 and GPR143 mutations respectively. The Lab also studied coronary virus of SARS and Schistosoma japonicum at transcriptome level, and elucidated the physiological and pathological features of Leptospira interrogans serovar lai strain, giving effective prevention and therapy strategies for communicable diseases.

    Owing to the above achievements, the Lab won a great number of important national and international awards, including Second prize of the Chinese National Natural Sciences Award (three times), Second Prize of National Science and Technology Progress Award (four times), Kettering Prize for cancer research, le Prix Mondial Cino del Duca, the Charles Rodolphe Brupbacher Prize for Cancer Research, Prix de l'Qise de La Legue Nationale contre le Cancer, Cheung Kong Scholars Achievement Award, ISI® Citation Classic Award, and etc.


    Cooperation 

  • Long-term collaborations with Samuel Waxman Cancer Research Foundation of US in leukemia research
  • Long-term collaborations with University Paris 7 in leukemia research
  •  State Key Laboratory of Medical Genomics