Ph.D., Professor, Principal Investigator
Laboratory of Tumor Genomics
Research Interests or Current Research Focus
Dr. Chen and his colleagues have been devoting efforts to investigate mechanisms of leukemogenesis and of leukemic cell differentiation and apoptosis, functional genomics of cancer, proteomics with the core of identifying leukemia-related interacting proteins, and the identification of leukemic drug targets in the treatment of induced differentiation.
Major Research Achievement
1. With a series of original experiments, our works on cellular and molecular mechanisms of arsenic trioxide (As2O3) in vitro and in vivo have been attracting worldwide interests. The related progresses have been published in PNAS, JNCI, BLOOD, Leukemia and others.
2. We reported recently that mild hypoxia and hypoxia mimetic agents cobalt chloride and desferrioxamine (DFO) can induce differentiation of human acute myeloid leukemic (AML) cellsin vitro and in vivo,acting via a hypoxia-inducible factor-1 alpha (HIF-1a), which interact physically with andincrease the transcriptional activity of CCAAT/enhancer binding protein alpha (C/EBPa), acritical factor for granulocytic differentiation. The related discoveries have been publishedin several journals such as Blood, Leukemia, Proteomics, Heamatologica, BBRC and Apoptosis.
3. We report that all-trans retinoic acid (ATRA) and PMA, effective differentiation-inducing agents of AML cells, can elevate phospholipid scramblase 1 (PLSCR1) expression by activated protein kinase Cd (PKCd). We also show that interferon-a induces expression of PLSCR1 through STAT1 requires sequential activation of PKCd & JNK. Decreasing PLSCR1 expression with small interfering RNA inhibits ATRA/PMA -induced differentiation. Taken together, these results suggest that as a protein induced upon PKCd activation, PLSCR1 is required for ATRA and PMA-triggered leukemic cell differentiation. The related discoveries have been publishedin Blood Oncogene and J Biol Chem.
4. As a promising new class of anticancer drugs, camptothecins have advanced to the forefront of several areas of therapeutic and developmental chemotherapy. We report that nanomolar concentrations of NSC606985, a rarely studied camptothecin analog, induces apoptosis in AML cells by NSC606985 by rapid induction of the proteolytic activation of PKCd with loss of mitochondrial transmembrane potential and caspase-3 activation. The following animal experiments showed its effectiveness in vivo to induce apoptosis and to elongate survival of leukemic mice. The related discoveries have been published in Blood an other journals.
5. We reported that AML1-ETO, a fusion protein of chromosome translocation (8;21) frequently occurred in AML, induced cell cycle arrest via upregulating connexin 43 expression and increased the sensitivity to intrinsic and extrinsic apoptosis. The related works have been published in Leukemia and J Cell Physiol.
1985-1988 M.D, Shanghai Second Medical University, Shanghai, China
1993-1996 Ph.D, Shanghai Second Medical University, Shanghai, China
Major Academic Appointments
1988-1993 Instructor, Department of Pathophysiology and Institute of Cardio Vascular Disease, Nanhua Univeristy,
Hunan Province, CHINA
1996-1999 Associate professor and professor, Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Second
Medical University (SSMU).
1997 Visiting Scholar, Institute of Hematology, Saint Louis Hospital, Paris, FRANCE
1998-1999 Deputy director of Dept. Biology (pluralist), SSMU, Shanghai, China.
1999-Present Vice Editor-in-Chief, Chinese Journal of Cancer
1999-2001 Visiting assistant professor, Dept. of Medicine, MountSinai School of Medicine, New York, USA
2001-2002 Professor and deputy director, Shanghai Institute of Hematology, Ruijin Hospital
2001-Present Professor and director, Division of Functional Genomics of Cancer, Institute of Health Science Center, SIBS, CAS
2002-Present Chairman, Dept. Pathophysiology, Shanghai Jiao Tong University School of Medicine
(Formerly Shanghai Second Medical University)
2005-Present Director, Key Laboratory of Cell Differentiation and Apoptosis, Ministry of Education, China
2006-Present Vice dean, Shanghai Jiao Tong University School of Medicine
Honors, Certificates, and Academic Society
2005: Awarded as "the Model Laborer in CHINA" by Chinese Central Government
2005: Awarded as "Hero-like Talent for Science and Technology, Shanghai Association of Science and Technology"
2004: Received the first prize of "Shanghai Medical Science and Technology Reward" by Shanghai branch of Chinese Medical Association
2004: Received "Chinese Young Science and Technology Prize" by Chinese Science and Technology Association
2004: Awarded as the member of "Thousands of Talents of China in the New Century" by Personnel Ministry of China
2004: Awarded as "the Model Laborer in Shanghai" by Shanghai Municipal Government
2003: Awarded as "the Outstanding Figure in Science" by Shanghai Science and Technology Committee
2003: Awarded as "the Excellent Overseas Returnees in Shanghai" by Shanghai Municipal Government
2002: Awarded as "Chief Scientist" of Key program of Basic Research by Chinese Ministry of Science and Technology
2002: Awarded as one of the Ten-Top Youths of Shanghai Municipal of China
2000: Received the "Dupont Innovation Reward" by Chinese Ministry of Science and Technology
2000: Received "National Nature Science Reward" by Chinese Government
2000: Awarded as "Scientist with the Important Contribution" by Chinese Government
1999: Received the "Silver-snake prize", a highest prize from the field of health and medicine in Shanghai Municipal of China
1999: Awarded as "Excellent Young Teacher" by Education Committee of Shanghai
1998: Awarded as "Life Science Prize" by MIN-ZHI Milk Co. of Japan
1997: Received first prize of "Shanghai Scientific and Technological Progress Reward" by Shanghai Municipal Government
1997: Awarded as "Excellent Young Teacher" by Education Committee of Shanghai
1997: Owned "Grant of Outstanding Young Talent" by National Ministry of Public Health of China
1997: Owned "Grant of Outstanding Young Scientist" by National Natural Science Foundation of China
1997: Owned "Grant of Pre-Star (Qin Min-Xin) Scientists" by Shanghai Municipal of China
- Li J, Xu Y, Long XD, Wang W, Jiao HK, Mei Z, Yin QQ, Ma LN, Zhou AW, Wang LS, Yao M, Xia Q, Chen GQ. Cbx4 Governs HIF-1α to Potentiate Angiogenesis of Hepatocellular Carcinoma by Its SUMO E3 Ligase Activity. Cancer Cell. 2014; 25(1): 118-31.
- Duan CW, Shi J, Chen J, Wang B, Yu YH, Qin X, Zhou XC, Cai YJ, Li ZQ, Zhang F, Yin MZ, Tao Y, Mi JQ, Li LH, Enver T, Chen GQ, Hong DL. Leukemia propagating cells rebuild an evolving niche in response to therapy. Cancer Cell. 2014; 25(6):778-93.
- Yin QQ, Liu CX, Wu YL, Wu SF, Wang Y, Zhang X, Hu XJ, Pu JX, Lu Y, Zhou HC, Wang HL, Nie H, Sun HD, Chen GQ. Preventive and Therapeutic Effects of Adenanthin on Experimental Autoimmune Encephalomyelitis by Inhibiting NF-κB Signaling. J Immunol. 2013 Sep 1;191(5):2115-25.
- Xia L, Wang TD, Shen SM, Zhao M, Sun H, He Y, Xie L, Wu ZX, Han SF, Wang LS, Chen GQ. Phosphoproteomics Study on the Activated PKCδ-Induced Cell Death. J Proteome Res. 2013 Oct 4;12(10):4280-301.
- Yang ZY, Jiang H, Qu Y, Wei M, Yan M, Zhu ZG, Liu BY, Chen GQ, Wu YL, Gu QL. Metallopanstimulin-1 Regulates Invasion and Migration of Gastric Cancer Cells Partially Through Integrin β4. Carcinogenesis. 2013; 34(12):2851-60.
- Gao YH, Li CX, Shen SM, Li H, Chen GQ, Wei Q, Wang LS. Hypoxia-inducible factor 1α mediates the down-regulation of superoxide dismutase 2 in von Hippel-Lindau deficient renal clear cell carcinoma. Biochem Biophys Res Commun. 2013 May 24;435(1):46-51.
- Liu CX, Zhou HC, Yin QQ, Wu YL, Chen GQ. Targeting peroxiredoxins against leukemia. Exp Cell Res. 2013 Jan 15;319(2):170-6.
- Wu ZX, Zhao M, Xia L, Yu Y, Shen SM, Han SF, Li H, Wang TD, Chen GQ, Wang LS. PKCδ enhances C/EBPα degradation via inducing its phosphorylation and cytoplasmic translocation. Biochem Biophys Res Commun. 2013 Apr 5;433(2):220-5.
- Liang YJ, Wang QY, Zhou CX, Yin QQ, He M, Yu XT, Cao DX, Chen GQ, He JR, Zhao Q. MiR-124 targets Slug to regulate epithelial-mesenchymal transition and metastasis of breast cancer. Carcinogenesis. 2013 Mar;34(3):713-22.
- He M, Wang QY, Yin QQ, Tang J, Lu Y, Zhou CX, Duan CW, Hong DL, Tanaka T, Chen GQ, Zhao Q. HIF-1α downregulates miR-17/20a directly targeting p21 and STAT3: a role in myeloid leukemic cell differentiation. Cell Death Differ. 2013 Mar;20(3):408-18.
- Liu CX, Yin QQ, Zhou HC, Wu YL, Pu JX, Xia L, Liu W, Huang X, Jiang T, Wu MX, He LC, Zhao YX, Wang XL, Xiao WL, Chen HZ, Zhao Q, Zhou AW, Wang LS, Sun HD, Chen GQ. Adenanthin targets peroxiredoxin I and II to induce differentiation of leukemic cells. Nat Chem Biol. 2012 Apr 8;8(5):486-93.
- Zhao M, Xia L, Chen GQ. Protein kinase cδ in apoptosis: a brief overview. Arch Immunol Ther Exp (Warsz). 2012 Oct;60(5):361-72.
- Huang J, Yan J, Zhang J, Zhu S, Wang Y, Shi T, Zhu C, Chen C, Liu X, Cheng J, Mustelin T, Feng GS, Chen GQ, Yu J. SUMO1 modification of PTEN regulates tumorigenesis by controlling its association with the plasma membrane. Nat Commun. 2012 Jun 19;3:911. doi: 10.1038/ncomms1919.
- Kua HY, Liu H, Leong WF, Li L, Jia D, Ma G, Hu Y, Wang X, Chau JF, Chen YG, Mishina Y, Boast S, Yeh J, Xia L, Chen GQ, He L, Goff SP, Li B. c-Abl promotes osteoblast expansion by differentially regulating canonical and non-canonical BMP pathways and p16(INK4a) expression. Nat Cell Biol. 2012 Jun 24;14(7):727-37.
- Duan X, Block E, Li Z, Connelly T, Zhang J, Huang Z, Su X, Pan Y, Wu L, Chi Q, Thomas S, Zhang S, Ma M, Matsunami H, Chen GQ, Zhuang H. Crucial role of copper in detection of metal-coordinating odorants. Proc Natl Acad Sci U S A. 2012 Feb 28;109(9):3492-7.
- Liu B, Zheng Y, Wang TD, Xu HZ, Xia L, Zhang J, Wu YL, Chen GQ, Wang LS. Proteomic Identification of Common SCF Ubiquitin Ligase FBXO6-Interacting Glycoproteins in Three kinds of Cells. J Proteome Res. 2012 Mar 2;11(3):1773-81.
- Wu L, Pan Y, Chen GQ, Matsunami H, Zhuang H. Receptor-Transporting Protein 1 Short (RTP1S) Mediates the Translocation and Activation of Odorant Receptors by Acting through Multiple Steps. J Biol Chem. 2012 Jun 22;287(26):22287-94.
- Wang LS, Xia L, Shen SM, Zheng Y, Yu Y, Chen GQ. Dissecting cell death with proteomic scalpels. Proteomics. 2012 Feb;12(4-5):597-606.
- Yang ZY，Qu Y, Zhang Q, Wei M, Liu CX, Chen XH, Yan M, Zhu ZG, Liu BY, Chen GQ, Wu YL, Gu QL. Knockdown of metallopanstimulin-1 inhibits NF-κB signaling at different levels: The role of apoptosis induction of gastric cancer cells. Int J Cancer, 2012 Jun 15;130(12):2761-70
Invited reviews, comments and book chapters
1. Huang Y, Zhao Q, Chen GQ.
Phospholipid scramblase 1.
Sino Acta Physiology. 2006 Dec 25;58(6):501-510.
2. Chen GQ, Peng ZG, Liu W, Song LP, Jiang Y, Huang Y, Zhao Q.
Hypoxia inducible factor-1alpha and leukemic cell differentiation.
Sino Acta Physiology 2006 Feb 25;58(1):5-13.
3. Fang J, Chen SJ, Tong JH, Wang ZG, Chen GQ, Chen Z.
Treatment of acute promyelocytic leukemia with ATRA and As2O3: a model of molecular target-based cancer therapy.
Cancer Biol Ther. 2002 Nov-Dec;1(6):614-20.
4. Chen Z, Chen GQ, Shen ZX, Sun GL, Tong JH, Wang ZY, Chen SJ.
Expanding the use of arsenic trioxide: leukemias and beyond.
Semin Hematol. 2002 Apr;39(2 Suppl 1):22-6.
5. Zhao WL, Chen SJ, Shen Y, Xu L, Cai X, Chen GQ, Shen ZX, Chen Z, Wang ZY.
Treatment of acute promyelocytic leukemia with arsenic trioxide: clinical and basic studies.
Leuk Lymphoma. 2001 Nov-Dec;42(6):1265-73.
6. Zhang TD, Chen GQ, Wang ZG, Wang ZY, Chen SJ, Chen Z.
Arsenic trioxide, a therapeutic agent for APL.
Oncogene. 2001 Oct 29;20(49):7146-53.
7. Chen Z, Chen GQ, Shen ZX, Chen SJ, Wang ZY.
Treatment of acute promyelocytic leukemia with arsenic compounds: in vitro and in vivo studies.
Semin Hematol. 2001 Jan;38(1):26-36.