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
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.
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.
Chao Chen, PhD; Assistant Scientist
Peng Zhao, PhD; Assistant Scientist
Narin Park, Undergraduate Student
Wen-Mei Yu, Lab Manager
Yan Y., L. Dong, J. Zhang, K. D. Bunting, E. Stieglitz, M. L. Loh, and C. K. Qu. JMML tumor cells suppress normal hematopoiesis by disrupting hematopoietic stem cell homeostasis through overproduction of IL-1β. Blood Advances. 2021. 6:200-206
Su H., M. Jiang, C. Senevirathne, S. Alri, T. Zhang, J. X. Ferrucio, N. T. Tran, S. M. Liu, G. Han, S. Jin, Y. Zhu, Q. Zhao, Y. Chen, S. Winski, Y. Shen, J. Liu, C. K. Qu, C. Klug, R. Bhatia, Y. Chen, S. Nimer, Y. G. Zheng, J. Jin, H. Deng, D. S. Krause, J. Xiang, A. Verma, M. Luo, X. Zhao. Arginine Methylation of Dual Specificity Phosphatase 4 Controls Cell Differentiation. Cell Reports. 2021; Jul 27;36(4):109421
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.
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.
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.
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.
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.
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.
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)