I direct a laboratory that focuses on the intracellular and extracellular signal network controlling the production, trafficking, function, and cell death of neutrophils during infection and inflammation. The ultimate goal is to develop more efficient and effective therapies for treating various infectious and inflammatory diseases as well as immune-related disorders. During the past fifteen years, my laboratory has contributed more than 40 publications, as articles in peer-reviewed journals, to the fields of neutrophil biology, inflammatory mechanisms and intervention, and AML therapy.
1. We identified PtdIns(3,4,5)P3/Akt pathway, reactive oxygen species (ROS), and protease 3 as key regulators of neutrophil spontaneous death.
2. We discovered that PtdIns(3,4,5)P3 signaling can be negatively regulated by InsP7 in neutrophils.
3. We discovered a novel and highly specific small-molecule TNFɑ inhibitor, which can be potentially used to treat TNFɑ-mediated inflammatory diseases.
4. We reported that inhibition of IP6K1 suppresses neutrophil-mediated pulmonary damage in bacterial pneumonia but efficiently and effectively enhances host bacterial killing. Therefore, IP6K1 is a promising therapeutic target for bacterial pneumonia.
5. We found that PRTN3 exerts an inhibitory effect on STAT3-dependent myeloid differentiation and could be a promising therapeutic target for the treatment of acute myeloid leukemia.
6. We discovered that activation of thermogenic adipose tissues (TATs) by cold exposure or β3-adrenergic receptor agonists markedly alleviated the development and progression of AML and ALL in mouse leukemia models.
MS, Pharmacology, Chinese Academy of Medical Sciences and Peking union Medical College, Beijing, China, 1996-2000
BS, Molecular Biology, Nankai University, Tianjin, China, 1988-1992
Principal Investigator, State Key Laboratory for Experimental Haematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 1992-
Visiting Scholar in Biology Dept, Hong Kong University of Science and Technology, 2006-2007
Visiting Scholar in Biology Dept, Hong Kong University of Science and Technology, 1998-1999
PRINCIPAL HONORS, AWARDS:
2013 The third grade prize of Natural Science Prize issued by Tianjin Municipal Government
2004 The First grade prize of Science and Technology Progress Prize issued by Tianjin Municipal Government
2001 The Second grade prize of Science and Technology Progress Prize issued by Tianjin Municipal Government
SELECTED PUBLICATIONS:
1. Chen, R#., Cheng, T#., Xie, S#., Sun, S., Chen, M., Zhao, S., Ruan, Q., Ni, S., Rao, M.,Quan, X., Chen, K., Zhang, S.,Cheng, T., Xu, Y*., Chen, Y.*, Yang, Y*.,and Cao,Y*. Effective treatment of acute leukemias in mice by activation of thermogenic adipose tissues. Advanced Science. 2024 Jul 25:e2402332. doi: 10.1002/advs.202402332.
2. Liu, H#., Sun, L#., Zhao, H., Zhao, Z., Zhang, S., Jiang, S., Cheng, T., Wang, X., Wang, T., Shao, Y., Zhu, H., Han, H., Cao, Y., Jiang, E., Cao, Y*., & Xu, Y.*. (2024). Proteinase 3 depletion attenuates leukemia by promoting myeloid differentiation. Cell death and differentiation. 2024;31(6):697-710. DOI:10.1038/s41418-024-01288-4.
3. Qingming Hou#, Fei Liu#, Anutosh Chakraborty. Yonghui Jia, Amit Prasad, Hongbo Yu, Li Zhao; Keqiang Ye, Solomon H, Solomon H. Snyder, Yuanfu Xu*, Hongbo R. Luo *. Inhibition of IP6K1 suppresses neutrophil-mediated pulmonary damage in bacterial pneumonia. Sci Transl Med, 2018 ,4;10(435):eaal4045.doi: 10.1126/scitranslmed.aal4045.
4. Fabien Loison, Haiyan Zhu, Kutay Karatepe, Anongnard Kasorn, Peng Liu, Keqiang Ye, Jiaxi Zhou, Shannan Cao, Haiyan Gong, Dieter E. Jenne, Eileen Remold-O’Donnell, Yuanfu Xu *, and Hongbo R. Luo *. Proteinase 3-dependant caspase-3 cleavage mediates neutrophil death and inflammation. J Clin Invest. 2014;124(10):4445-58.
5. Li Ma, Haiyan Gong, Haiyan Zhu, Qing Ji, Peng Liu, Shannan Cao, Jianfeng Yao, Pei Shu, Mingzhe Han, Xiaotong Ma, Dongsheng xiong, Hongbo R. Luo,Fei Wang, Jiaxi Zhou* &Yuanfu Xu*. A Novel Small-molecule TNFα Inhibitor Attenuates Inflammation in a Hepatitis Mouse Model. J Bio Chem, 2014;289:12457-12466.
6. Xu Y, Li H, Bajrami B, Kwak H, Cao S, Liu P, Zhou J, Zhou Y, Zhu H, Ye K, Luo HR*. Cigarette smoke(CS) and nicotine delay neutrophil spontaneous death via suppressing production of diphosphoinositol pentakisphosphate. PNAS. 2013;110(19):7726-31.
7. Yuanfu Xu#, Fabien Loison#, and Hongbo R. Luo* . Neutrophil spontaneous death is mediated by downregulation of autocrine signaling through GPCR, PI3Kγ, ROS, and actin. PNAS. 2010;107: 2950–2955.