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 knowledge gained from these studies to develope novel therapeutics or to improve current treatment for related blood disorders.
- 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
Hong Zheng, PhD; Postdoctoral Fellow
Fang Ni, PhD; Postdoctoral Fellow
Zhiguo Li, Ph.D.; Postdoctoral Fellow
Chao Chen, Ph.D.; Postdoctoral Fellow
Qianjin Li, Ph.D.; Postdoctoral Fellow
Xinyi Wang; M.S. Student
Wen-Mei Yu; Lab Manager
Ashruth Reddy; Undergraduate Student
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 the Press Release for Nature and Nature research journals, May 24, 2009 (http://www.nature.com/ncb/press_release/ncb0509.html).
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
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
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
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 a Research Highlight in Nature Reviews Molecular and Cell Biology (2013; 14:64) (http://www.nature.com/nrm/journal/v14/n2/full/nrm3515.html) and in an Editorial in Cell Stem Cell (2013; 12:1-3) (http://www.sciencedirect.com/science/article/pii/S1934590912007102).
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
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
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
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; doi:10.1038/nature19479) (http://www.nature.com/nature/journal/vaop/ncurrent/full/nature19479.html) and in Research Watch in Cancer Discovery (2016; 6:1302-1302) (http://cancerdiscovery.aacrjournals.org/content/6/12/1302.2), and Emory News Release (http://news.emory.edu/stories/2016/10/bad_neighbors_nature_qu_ptpn11/).
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., 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
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 Releases. (http://news.emory.edu/stories/2018/03/qu_shp2_noonan/index.html).
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
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
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 (https://news.emory.edu/stories/2018/10/cerebellum_ckqu_sciadvances/index.html).
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
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 (http://news.emory.edu/stories/2019/03/qu_aminoacids_leukemia/index.html), Science Daily (https://www.sciencedaily.com/releases/2019/03/190312123803.htm), and Medicalxpress (https://medicalxpress.com/news/2019-03-starving-leukemia-cells-amino-acids.html).
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
POST-DOCTORAL POSITION AVAILABLE
A post-doctoral position is available 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 (Science Signaling. 2018; 11 (522), eaao1591. Nature. 2016; 539:304-308; PNAS. 2016, 113:984-989; Blood, 2015, 125:1562-5; Cell Stem Cell. 2013, 12:62-74; J. Exp. Med. 2011, 208:1977-1988). 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. Candidates should have a Ph.D. degree with a strong background in molecular biology and cell biology. Previous experience in cell signaling and experimental hematology is preferable. Interested individuals should send their curriculum vitae and the names and addresses of three references to:
C. K. Qu, M.D., Ph.D.
Department of Pediatrics, Division of Hematology/Oncology
Aflac Cancer and Blood Disorders Center
Children’s Healthcare of Atlanta
Emory University School of Medicine
1760 Haygood Drive NE, HSRB E302
Atlanta, GA 30322