Research Overview

Cell signaling and metabolic regulation of normal hematopoiesis and leukemogenesis with a focus on stem cells.

By studying a group of enzymes called phosphatases (protein and lipid phosphatases), our research team strives to identify the signaling and metabolic mechanisms that are crucial for normal hematopoiesis, and aberrant regulation of which is associated with hematologic disorders. Furthermore, we attempt to use the kowledge gained from these studies to develope novel therapeutics to improve current treatments for related blood disorders.

  • Cellular and molecular mechanisms by which activating mutations of PTPN11 cause leukemias
  • Experimental therapeutics for PTPN11 mutation-associated leukemias
  • Metabolic regulation of hematopoietic stem cells and leukemic stem cells

POST-DOCTORAL POSITION 

Job Description:  

To investigate the molecular mechanisms by which genetic mutations of protein tyrosine phosphatase PTPN11 (SHP2) induce childhood leukemias, and to use this knowledge to develop novel therapeutics for these diseases. Research in our laboratory is centered on the signaling and metabolic mechanisms involved in normal and malignant hematopoiesis. We are particularly interested in the regulation by protein and lipid phosphatases, including PTPN11, in hematopoietic stem cell biology and in leukemogenesis. A variety of experimental approaches, such as mouse genetics, biochemical, and stem cell technologies are undertaken in these studies.

Qualifications:

Candidates should have a PhD degree with a strong background in molecular biology and cell biology. Previous experience in cell signaling and experimental hematology is preferable.

Contact:

Interested individuals should send their curriculum vitae and the names and addresses of three references to cheng-kui.qu@emory.edu.

Chao Chen, PhD; Assistant Scientist

Peng Zhao, PhD; Assistant Scientist

Narin Park, Undergraduate Student

Yuhan Yan, Emory School of Medicine International Exchange Program MD Student

Wen-Mei Yu, Lab Manager

Hu L., F. Ni, X. Wang, M. E. Fay, K. M. Young, W. A. Lam, T. A. Sulchek, and C. K. Qu. Decreased cell stiffness enhances leukemia development and progression. Leukemia. 2020, Feb 24. doi: 10.1038/s41375-020-0763-7.

 

Ni F., W. M. Yu, X. Wang, M. E. Fay, K. Young, Y. Qiu, W. A. Lam, T. A. Sulchek, T. Cheng, D. T. Scadden, and C. K. Qu. Ptpn21 controls hematopoietic stem cell homeostasis and biomechanics. Cell Stem Cell. 2019; 24:1-13. 

Featured in: Emory News Release, MedicalXpress, Business Standard , Science Daily

 

Ni F., W. M. Yu, Z. Li, D. K. Graham, L. Jin, S. Kang, M. R. Rossi, S. Li, H. E. Broxmeyer, and C. K. Qu. Critical role of ASCT2-mediated amino acid metabolism in promoting leukemia development and progression. Nature Metabolism. 2019; 1:390-403. 

Featured in News & Views in Nature Metabolism (2019; 1:308–309), Emory News Release, Science Daily, MedicalXpress, EurekAlert

 

Hayashi Y., Y. Zhang, A. Yokota, X. Yan, J. Liu, K. Choi, B. Li, G. Sashida, Y. Peng, Z. Xu, R. Huang, L. Zhang, G. M. Freudiger, J. Wang, Y. Dong, Y. Zhou, J. Wang, L. Wu, J. Bu, A. Chen, X. Zhao, X. Sun, K. Chetal, A. Olsson, M. Watanabe, L. E. Romick-Rosendale, H. Harada, L. Y. Shih, W. Tse, J. P. Bridges, M. A. Caligiuri, T. Huang, Y. Zheng, D. P. Witte, Q. F. Wang, C. K. Qu, N. Salomonis, H. L. Grimes, S. D. Nimer, Z. Xiao, and G. Huang. Pathobiologic Pseudohypoxia as a Putative Mechanism Underlying Myelodysplastic Syndromes. Cancer Discovery. 2018; 8:1438-1457

 

Jin L., J. Chun, C. Pan, A. Kumar, G. Zhang, Y. Ha, D. Li, G. N. Alesi, Y. Kang, L. Zhou, W. M. Yu, K. R. Magliocca, F. R. Khuri, C. K. Qu, C. Metallo, T. K. Owonikoko, and S. Kang. The PLAG1-GDH1 axis promotes anoikis resistance and tumor metastasis through CamKK2-AMPK signaling in LKB1-deficient lung cancer. Molecular Cell. 2018; 69:87-99

 

Zheng H., W. M. Yu, J. Shen, S. Kang, D. Hambardzumyan, J. Y. Li, Y. Shen, A. M. Kenney, J. Chen, and C. K. Qu. Mitochondrial oxidation of the carbohydrate fuel is required for neural precursor/stem cell function and postnatal cerebellar development. Science Advances. 2018; 4: eaat2681. 

Featured in: Emory News Release, Science Daily, EurekAlert, Biocompare News

 

Stavrou E. X., C. Fang, K. L. Bane, E. Kucukal, L. V. Nayak, A. Merkulova, S. Izadmehr, M. M. Mumaw, C. C. Reynolds, O. Alhalabi, W. M. Yu, C. K. Qu, U. A. Gurkan, H. J. Meyerson, M. T. Nieman, A. H. Schmaier. Factor XII - uPAR Upregulate Neutrophil Functions to Influence Wound Healing. The Journal of Clinical Investigation. 2018; 128:944-959

 

Jin L., J. Chun, C. Pan, D. Li, R. Lin, G. N. Alesi, X. Wang, H. B. Kang, L. Song, D. Wang, G. Zhang, J. Fan, T. J. Boggon, L. Zhou, J. Kowalski, C. K. Qu, C. E. Steuer, G. Z. Chen, N. F. Saba, L. H. Boise, T. K. Owonikoko, F. R. Khuri, K. R. Magliocca, D. M. Shin, S. Lonial, and S. Kang. MAST1 drives cisplatin resistance in human cancers by rewiring cRaf independent MEK activation. Cancer Cell. 2018; 34(2):315-330

 

Zheng H., W. M. Yu, R. R. Waclaw, M. I. Kontaridis, B. G. Neel, and C. K. Qu. Gain-of-function mutations in protein tyrosine phosphatase Ptpn11 (Shp2) induce hydrocephalus in a catalytically-dependent manner. Science Signaling. 2018; 11 (522), eaao1591. 

Featured in: Emory News Release, MedicalXpress, Science and Technology Research News

 

Dong L., H. Zheng, and C. K. Qu. CCL3 is a key mediator for the leukemogenic effect of Ptpn11 activating mutations in the stem cell microenvironment. Blood. 2017; 130:1471-1474

 

Liu W., W. M. Yu, J. Zhang, R. J. Chan, M. L. Loh, Z. Zhang, K.D. Bunting, and C. K. Qu. Inhibition of the Gab2/PI3K/mTOR signaling ameliorates the myeloid malignancy caused by Ptpn11 (Shp2) gain-of-function mutations. Leukemia. 2017; 31:1415-1422

 

Dong, L., W.M. Yu, H. Zheng, M. L. Loh, S. T. Bunting, M. Pauly, G. Huang, M. Zhou, H. E. Broxmeyer, D. T. Scadden, and C. K. Qu. Leukemogenic effects of Ptpn11 (Shp2) activating mutations in the stem cell microenvironment. Nature. 2016; 539:304-308. 

Featured in: News and Views in Nature [2016;539(7628):173-175], Research Watch in Cancer Discovery (2016; 6:1302-1302), Emory News Release, CHOA News Release, Science Daily, Stem Cell Portal

 

Gu L., H. Zhang, T. Liu, S. Zhou, Y. Du, J. Xiong, S. Yi, C. K. Qu, H. Fu, and M. Zhou. Discovery of dual inhibitors of MDM2 and XIAP for cancer treatment. Cancer Cell. 2016; 30: 623-636

 

Liu, X., H. Zheng, X. Li, S. Y. Wang, H. J. Meyerson, W. Yang, B. G. Neel, and C. K. Qu. Gain-of-function mutations of Ptpn11 (Shp2) cause aberrant mitosis and increase susceptibility to DNA damage-induced malignancies. Proceedings of the National Academy of Sciences of the United States of America. 2016; 113:984-989

 

Liu, X., H. Zheng, T. M. W. M., Yu, Cooper, K. D. Bunting, and C. K. Qu. Maintenance of hematopoietic stem cells ex vivo by reprograming cellular metabolism. Blood. 2015; 125:1562-1565

Recommended as being of special significance in its field by Faculty of 1000

 

Yu, W. M., X. Liu, J. Shen, J. Jovanovic, E. E. Pohl, S. L. Gerson, T. Finkel, H. E. Broxmeyer, and C. K. Qu. Metabolic regulation by the mitochondrial phosphatase PTPMT1 is required for hematopoietic stem cell differentiation. Cell Stem Cell. 2013; 12:62-74. 

Featured in: Research Highlight in Nature Reviews Molecular and Cell Biology (2013; 14:64) and Editorial in Cell Stem Cell (2013; 12:1-3)

 

Liu, X., H. Zheng, and C. K. Qu. Protein tyrosine phosphatase Shp2 (Ptpn11) plays an important role in maintenance of chromosome stability. Cancer Research. 2012; 72:5296-5306

 

Xu, D., X. Liu, W. M. Yu, H. Meyerson, C. Guo, S. L. Gerson, and C. K. Qu. Non-lineage/stage restricted effects of a gain-of-function mutation in tyrosine phosphatase Ptpn11 (Shp2) on leukemia stem cell development. The Journal of Experimental Medicine. 2011; 208:1977-1988

 

Xu, D., S. Wang, W. M. Yu, Chan, T. Araki, K. D. Bunting, B. G. Neel, and C. K. Qu. A germline gain-of-function mutation in Ptpn11 (Shp2) phosphatase induces myeloproliferative disease by aberrant activation of hematopoietic stem cells. Blood. 2010; 116:3611-3621

 

Shen, J., W. M. Yu, M. Brotto, J. A. Scherman, C. Guo, C. Stoddard, T. M. Nosek, H. H. Valdivia, and C. K. Qu. Deficiency of phosphatidylinositol phosphate phosphatase MIP/MTMR14 induces a muscle disorder by disrupting Ca2+ homeostasis. Nature Cell Biology. 2009; 11:769-776. 

Featured in: Press Release for Nature and Nature research journals, May 24, 2009 (http://www.nature.com/ncb/press_release/ncb0509.html)