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Prof. LIU Qingsong
Time:2014-07-18
 

LIU Qingsong

Title

Vice Director of MR Life Science Division

Education Background

Ph.D.

Major

Cancer Chemical Biology

       
 
LIU Qingsong obtained his B.S degree from Nankai University in 2001, and his Ph.D. degree of Chemistry from Texas A&M University in 2006. Then he moved to Harvard Medical School for postdoctoral training and in 2007 he joined Dana Faber Cancer institute as a Research fellow. In 2011, he was promoted to research scientist . In 2012, Dr. Liu joined CHMFL to explore the translational cancer research with the help of high magnetic field mediated instrumentations. Dr. Liu has over 40 publications including papers in peer-reviewed journals, book chapters and patents and the work has been cited over 1500 times.
 

Education Background

2006     Ph.D. Texas A&M University, Advisor: Prof. Gray A. Sulikowski

2001     B.S. Department of Chemistry, NanKai University

 

Professional Activities

2012.7-present   Professor, High Magnetic Field Laboratory, Chinese Academy of Sciences

2011.2-2012.7    Research scientist, Dept.of Cancer Biology, Dana Farber Cancer Institute, Harvard Medical School.

                                Advisor: Prof. Nathanael S. Gray 
 2007.11-2011.2   Research fellow, Dept.Cancer Biology, Dana Farber Cancer Institute, Harvard Medical School.

                                Advisor: Prof. Nathanael S. Gray 
 2006.9-2007.11   Postdoc fellow, Dept.of Biological Chemistry and Molecule Pharmacology, Harvard Medical School.

                                Advisor: Prof. Robert R. Rando 

 

Research

 

Research Interests

1. NMR mediated Fragment/Structural Based Drug design for kinase-targeting anti-cancer drug discovery
2. Bio/Chemo informatics mediated computational biology/chemistry
3. Drug resistance/sensitivity mechanistic study
4. System biological mechanistic study/redevelopment of Chinese herbal remedy

 

Our team is focused on the signaling transduction pathway mediated translational medical research that aims to answer the clinical raised fundamental pathological questions from the basic research perspective and fulfill unmet medical needs from drug discovery point of view. To do this, we integrate multiple disciplines such as Chemistry, Biochemistry, Medicinal Chemistry, Chemical Biology, Structural Biology, Molecule Biology, Pharmacology, Bioinformatics and Pathology into the whole chain of drug discovery pipeline by application of Structural Based Drug design, Computer Aided Drug Design, NMR Mediated Fragment Based Drug Design, High Throughput Drug Screening and Combination Drug Regime Design technologies or concepts. We are specially interested in the kinase associated deregulated signaling transduction pathway in varies disease contexts and try to employ the newly in house developed small molecule probes to address the fundamental pathological questions such as tumorigenesis and drug resistance mechanisms and subsequently develop the small molecule drugs to control the diseases.

Specifically, our research is divided into three different but related areas.

1. Small molecule probes discovery and development: We are trying to apply the SBDD, FBDD and CADD as well as chemical informatics strategies to develop variety of different mechanism based small molecule probes such as irreversible protein binding probes, reversible DNA replicating probes etc. In the meanwhile, we are validating the therapeutic potential of biological targets by application of such probes via the proof of concept preclinical evaluation and subsequently developing drug like candidate for the clinical trials.

2. Drug resistance mechanistic study: we are trying integrating the Chemical Biology and Molecule Biology to address the drug resistance problems in the clinic. Both the drug treatment induced on target acquired mutation resistance and intrinsic signal pathway adaptive resistance are critical fundamental problems for target therapies. By employing chemical genetics approaches in the complementary of traditional genetic technologies we try to reveal the basic mechanisms of such problems and in the meanwhile employing system biology concept to search for the rational drug combination therapies to confer the drug resistance via high throughput screening and knowledge based combination design.
3.Natural products drugs re-discovery: Chinese herbal regimes have provides a huge library of the bio-active natural product/s and have been validated in the long history of clinical application. We are trying to employ the new system biology concept and integrate the NMR and LC-MS based metabonomics to study the proper bio-active ingredients combinations and in the meanwhile reveal the mechanism from the systematic signal transduction pathway network point of view. In addition, this new approach will provide the theoretical base and direction for the emerging selective single agent combination therapy development. 

 

Selected Publications

  1.  "Identification of Wee1 as a novel therapeutic target for mutant RAS-driven acute leukemia and other malignancies." Ellen Weisberg, Atsushi Nonami, Zhao Chen, Feiyang Liu, Jianming Zhang, Martin Sattler, Erik Nelson, Kristen Cowens, Amanda Christie, Constantine Mitsiades, Kwok-Kin Wong, Qingsong Liu, Nathanael Gray, and James Griffin*. Leukemia, 2014, doi:10.1038/leu.2014.149.
  2.  "Exploration of Type II Binding Mode: A Privileged Approach for Kinase Inhibitor Focused Drug Discovery?" Zheng Zhao, Hong Wu, Li Wang, Yi Liu, Stefan Knapp, Qingsong Liu*, Nathanael S. Gray*, ACS. Chem. Biol, 2014, doi:10.1021/cb500129t.
  3.  "Interleukin-6 secretion by astrocytes is dynamically regulated by PI3K-mTOR-calcium signaling." Codeluppi S, Fernandez Zafra T, Kjell J, Sandor K, Liu Q, Abrams M, Olson L, Gray NS, Svensson CI, Uhlén P, PloS ONE, 2014, 9(3): e92649.
  4. "Discovery of a Potent, Covalent BTK Inhibitor for B-Cell Lymphoma."Hong Wu, Wenchao Wang, Feiyang Liu, Ellen E. Weisberg, Bei Tian, Yongfei Chen, Binhua Li, Aoli Wang , Beilei Wang, Zheng Zhao, Douglas W. McMillin, Chen Hu, Hong Li, Jinhua Wang, Yanke Liang, Sara J. Buhrlage, Junting Liang, Jing Liu, Guang Yang, Jennifer R. Brown, Steven P. Treon, Constantine S. Mitsiades, James Griffin, Qingsong Liu*, Nathanael S. Gray* ACS Chem Biol. 2014, DOI: 10.1021/cb4008524.
  5. "Discovery of a potent and selective DDR1 receptor tyrosine kinase inhibitor." Kim HG, Tan L, Weisberg EL, Liu F, Canning P, Choi HG, Ezell SA, Wu H, Zhao Z, Wang J, Mandinova A, Griffin JD, Bullock AN, Liu Q*, Lee SW*, Gray NS*. ACS Chem Biol. 2013 ,8(10):2145-50.
  6. "Discovery of a selective irreversible BMX inhibitor for prostate cancer." Feiyang Liu, Xin Zhang, Ellen Weisberg, Sen Chen, Wooyoung Hur, Hong Wu, Zheng Zhao, Wenchao Wang, Mao Mao, Changmeng Cai, Nicholas I. Simon, Takaomi Sanda, Jinhua Wang, A. Thomas Look, James D. Griffin, Steve Balk*, Qingsong Liu*, Nathanael S. Gray*, ACS Chemical Biology, 2013, 8 (7), 1423–1428
  7. "Metabolic and functional genomic studies identify deoxythymidylate kinase as a target in LKB1-mutant lung cancer." Liu Y, Marks K, Cowley GS, Carretero J, Liu Q, Nieland TJ, Xu C, Cohoon TJ, Gao P, Zhang Y, Chen Z, Altabef AB, Tchaicha JH, Wang X, Choe S, Driggers EM, Zhang J, Bailey ST, Sharpless NE, Hayes DN, Patel NM, Janne PA, Bardeesy N, Engelman JA, Manning BD, Shaw RJ, Asara JM, Scully R, Kimmelman A, Byers LA, Gibbons DL, Wistuba II, Heymach JV, Kwiatkowski DJ, Kim WY, Kung AL, Gray NS, Root DE, Cantley LC, Wong KK, Cancer Discov. 2013 Aug;3(8):870-9
  8. "Chaperones as thermodynamic sensors of drug-target interactions reveal kinase inhibitor specificities in living cells." Mikko Taipale, Irina Krykbaeva, Luke Whitesell, Sandro Santagata, Jianming Zhang, Qingsong Liu, Nathanael S. Gray, and Susan Lindquist*  Nature Biotechnology, 2013, 31(7):630-7.
  9. "A simple, highly visual in vivo screen for anaplastic lymphoma kinase inhibitors." Frederico S.L.M. Rodrigues , Xueyan Yang , Masataka Nikaido, Qingsong Liu , Robert N Kelsh*  ACS Chem. Biol. 2012, Dec 21;7(12):1968-74
  10. "Combined inhibition of mTORC1 and mTORC2 signaling pathways is a promising therapeutic option in inhibiting pheochromocytoma tumor growth: in vitro and in vivo studies in female athymic nude mice." Giubellino A*, Bullova P, N?lting S, Turkova H, Powers JF, Liu Q, Guichard S, Tischler AS, Grossman AB, Pacak K*. Endocrinology, 2013, 154: 646-655
  11. "Selective Akt inhibitors synergize with tyrosine kinase inhibitors and effectively override stroma-associated cytoprotection of mutant FLT3-positive AML cells." Ellen Weisberg*, Qingsong Liu*, Xin Zhang, Erik Nelson, Martin Sattler, Feiyang Liu, Maria Nicolais, Jianming Zhang, Constantine Mitsiades, Robert Smith, Richard Stone, Ilene Galinsky, Atsushi Nonami, James D. Griffin, and Nathanael Gray. PLOS ONE, 2013, 8(2):e56473
  12. "Inhibitor-sensitive FGFR2 and FGFR3 mutations in lung squamous cell carcinoma." Rachel G. Liao, Joonil Jung, Matthew D. Wilkerson, Andrey Sivachenko, Qingsong Liu , Trevor J. Pugh , Chandra Sekhar Pedamallu , D. Neil Hayes , Nathanael S. Gray , Gad Getz , Robert I. Haddad , Matthew Meyerson* Cancer Research, 2013, 73(16):5195-205
  13. "Pharmacological inhibition of Eph receptors enhances glucose-stimulated insulin secretion from mouse and human pancreatic islets." Ruchi Jain, Deepak Jain, Qingsong Liu, Desiree Schumann, Peter Eickelmann, Lorenzo Piemonti, Nathanael S. Gray, Eckhard Lammert,*  Diabetologia, 2013, 56(6):1350-5.
  14. "The influence of hypoxia on CML trafficking through modulation of CXCR4 and E-cadherin expression." Azab AK, Weisberg E, Sahin I, Liu Feiyang, Awwad R, Azab F, Liu Qingsong, Griffin JD, Ghobrial IM. Leukemia, 2013 Apr;27(4):961-4
  15. "Kinase Inhibitors Targeting Anti-angiogenesis as Anti-cancer Therapies." Jing Liu, Feiyang Liu, David L. Waller, Junfeng Wang, Qingsong Liu* .Current Angiogenesis , 2012, 1(4), 335-346.
  16. "Developing irreversible inhibitors of the protein kinase cysteinome." Qingsong Liu, Lyn H. Jones, Yogesh Sabnis, Zheng Zhao, Tinghu Zhang, Nathanael S. Gray*. Chemistry & Biology, 2013,20(2):146-59
  17. "The ALK(F1174L) mutation potentiates the oncogenic activity of MYCN in neuroblastoma."Teeara Berry, William Luther, Yann Jamin1, Namrata Bhatnagar,, Winston A. Vetharoy, Takaomi Sanda, Christina Scho?nherr, Bandana Sharma , Albert Hallsworth, Karen Barker, Zahida Ahmad, Dorine Bax, Hannah Webber, Lisa Moreau, Qingsong Liu, Lynsey Vaughan, Wenchao Wang, Andrew Pearson, Antonio Perez-Atayde, Bengt Hallberg, Scott Rodig, Chris Jones, Simon Robinson, Nathanael Gray, Suzanne A. Eccles, Louis Chesler*, Rani E. George* .Cancer Cell , 2012, Jul 10;22(1):117-30
  18. "Characterization of Torin2, an ATP-competitive inhibitor of mTOR, ATM, and ATR." Qingsong Liu, Chunxiao Xu , Sivapriya Kirubakaran, Xin Zhang, Wooyoung Hur, Yan Liu, Nicholas P. Kwaitkowski, Jinhua Wang, Kenneth Westover, Peng Gao, Dalian Erica,  Carson C. Thoreen, Seong A. Kang, Matthew P. Patricelli, Pasi A. Janne, Kwok Wong, David M.Sabatini, Nathanael S. Gray*.Cancer Research, 2013,73(8):2574-2586
  19. "Using combination therapy to override stromal-mediated chemoresistance in mutant FLT3-positive AML: synergism between FLT3 inhibitors, dasatinib/multi-targeted inhibitors and JAK inhibitors." Ellen Weisberg*, Qingsong Liu*, Erik Nelson, Andrew L. Kung, Amanda L. Christie, Rod Bronson, Martin Sattler, Takaomi Sanda, Zheng Zhao, Wooyoung Hur, Constantine Mitsiades, Robert Smith, John F. Daley, Richard Stone, Ilene Galinsky, James D. Griffin, and Nathanael Gray. Leukemia, 2012, Oct;26(10):2233-44. (*Co-first author)
  20. "Functional characterization of an isoform-selective inhibitor of PI3K-p110β as a potential anticancer agent." Jing Ni!, Qingsong Liu!, Shaozhen Xie, Coby Carlson, Thanh Von, Kurt W. Vogel, Steve M. Riddle, Cyril H. Benes, Michael Eck, Thomas M. Roberts, Nathanael S. Gray,* Jean J. Zhao*. Cancer Discovery, 2012. 425-433. (!: Co-first authors)
  21. "Selective ATP-competitive inhibitors of TOR suppress rapamycin-insensitive function of TORC2 in Saccharomyces cerevisiae." Qingsong Liu!, Tao Ren!, Tara Fresques!, Wolfgang Oppliger, Brad J. Niles, Wooyoung Hur, David Sabatini, Michael N. Hall, Ted Powers, Nathanael S. Gray* . ACS Chemical Biology, 2012, 7(6):982-7 (!: Co-first authors)
  22. "Systematic identification of genomic markers of drug sensitivity in cancer cells."  Mathew J. Garnett*, Elena E. Edelman,*, Sonja J. Heidorn, Chris Greenman, Anahita Dastur, Ian Richard Thompson, Pat Greninger, Jorge Soares, Xi N. Luo, King Wai Lau, Qingsong Liu, Francesco Lorio, Randy J. Milano, Graham Bignell, Ah T. Tam, Helen Davies, Jesse A. Stevenson, Andrew Barthorpe, Stephen R. Lutz, Anne McLaren-Douglas, Xeni Mitropoulos, Tatiana Mironenko, Helen Thi, Laura Richardson, Wenjun Zhou, Frances Jewitt, Tinghu Zhang, Patrick O’Brien, Wooyoung Hur, Wanjuan Yang, Xianming Deng, Adam Butler, Hwan Geun Choi, Jae Won Chang, Jose Baselga, Ivan Stamenkovic, Jeffrey A. Engelman, Sreenath V. Sharma, Julio Saez-Rodriguez, Nathanael S. Gray, Jeffrey Settleman, P. Andrew Futreal, Daniel A. Haber, Michael R. Stratton, Sridhar Ramaswamy, Ultan McDermott, Cyril H. Benes. Nature, 2012, 483(7391):570-5.
  23. "Kinome-wide selectivity profiling of ATP-competitive mammalian target of rapamycin (mTOR) inhibitors and characterization of their binding kinetics." Qingsong Liu, Sivapriya Kirubakaran, Wooyoung Hur, Mario Niepel, Kenneth Westover, Carson C. Thoreen, Jinhua Wang, Jing Ni, Matthew P. Patricelli, Kurt Vogel, Steve Riddle, David L. Waller, Ryan Traynor, Takaomi Sanda, Seong A. Kang, Jean, Zhao, A. Thomas Look, Peter K. Sorger, David M. Sabatini, Nathanael S. Gray* . J. Bio. Chem, 2012, 287(13):9742-52.
  24. "Natural products as kinase inhibitors." Jing Liu, Yi Hu, David L. Waller, Junfeng Wang, Qingsong Liu*. Natural Products Reports , 2012 ,29(3):392-403.
  25. "Anti-HCV drugs in the pipeline." Priscilla L Yang. Min Gao; Kai Lin, Qingsong Liu, Valerie A Villareal.  Current Opinion in Virology, 2011, 1(6):607-16.
  26. "The controversial links among calorie restriction, SIRT1, and resveratrol."Yi Hu, Jing Liu, Junfeng Wang, Qingsong Liu*. Free radical biology and Medicine, 2011, 51(2), 250-256.
  27. "Systemic inhibition of the mammalian target of rapamycin (mTOR) pathway reduces neuropathic pain in mice."Ilona Obara, Keri K. Tochiki, Sandrine M. Géranton, Fiona B. Carr, Bridget M. Lumbc, Qingsong Liu, Stephen P. Hunt. Pain, 2011, 152(11), 2582-95.
  28. "Characterization of a selective inhibitor of the Parkinson's disease kinase LRRK2." Xianming Deng, Nicolas Dzamko, Alan Prescott, Paul Davies, Qingsong Liu, Qingkai Yang, Jiing-Dwan Lee, Matthew P. Patricelli, Tyzoon K. Nomanbhoy, Dario R. Alessi, and Nathanael S. Gray. Nature Chemical Biology, 2011, 203-205.
  29. "Discovery and optimization of potent and selective benzonaphthyridinone analogs as small molecule mTOR inhibitors with improved mouse microsome stability."  Qingsong Liu, jinhua Wang, Seong A. Kang, Carson, C. Thoreen, wooyoung Hur, Nathanael Gray, David Sabatini. Bioorg. Med. Chem. Lett, 2011, 4036-4040.
  30. "Discovery of 9-(6-aminopyridin-3-yl)-1-(3-(trifluoromethyl)phenyl)benzo[h][1,6]naphthyridin-2(1H)-one (Torin2) as a potent, selective, and orally available mammalian target of rapamycin (mTOR) inhibitor for treatment of cancer." Qingsong Liu, Jinhua Wang, Seong A. Kang, Carson, C. Thoreen, Nathanael Gray, David Sabatini. J. Med. Chem, 2011, 54, 1473-1480.