Browsing by Author "Liu, Wei"

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    Emerging tick-borne infections in mainland China: an increasing public health threat
    (Elsevier, 2015-12) Fang, Li-Qun; Liu, Kun; Li, Xin-Lou; Liang, Song; Yang, Yang; Yao, Hong-Wu; Sun, Ruo-Xi; Sun, Ye; Chen, Wan-Jun; Zuo, Shu-Qing; Ma, Mai-Juan; Li, Hao; Jiang, Jia-Fu; Liu, Wei; Yang, X. Frank; Gray, Gregory C.; Krause, Peter J.; Cao, Wu-Chun; Department of Microbiology & Immunology, IU School of Medicine
    Since the beginning of the 1980s, 33 emerging tick-borne agents have been identified in mainland China, including eight species of spotted fever group rickettsiae, seven species in the family Anaplasmataceae, six genospecies in the complex Borrelia burgdorferi sensu lato, 11 species of Babesia, and the virus causing severe fever with thrombocytopenia syndrome. In this Review we have mapped the geographical distributions of human cases of infection. 15 of the 33 emerging tick-borne agents have been reported to cause human disease, and their clinical characteristics have been described. The non-specific clinical manifestations caused by tick-borne pathogens present a major diagnostic challenge and most physicians are unfamiliar with the many tick-borne diseases that present with non-specific symptoms in the early stages of the illness. Advances in and application of modern molecular techniques should help with identification of emerging tick-borne pathogens and improve laboratory diagnosis of human infections. We expect that more novel tick-borne infections in ticks and animals will be identified and additional emerging tick-borne diseases in human beings will be discovered.
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    Inhibition of the Gab2/PI3K/mTOR signaling ameliorates myeloid malignancy caused by Ptpn11 (Shp2) gain-of-function mutations
    (Springer Nature, 2017-06) Liu, Wei; Yu, Wen-Mei; Zhang, Jing; Chan, Rebecca J.; Loh, Mignon L.; Zhang, Zheng; Bunting, Kevin D.; Qu, Cheng-Kui; Pediatrics, School of Medicine
    Activating mutations, such as E76K and D61Y, in PTPN11 (SHP2), a protein tyrosine phosphatase implicated in multiple cell signaling processes, are associated with 35% of patients with juvenile myelomonocytic leukemia (JMML), an aggressive childhood myeloproliferative neoplasm (MPN). Here we show that the interaction between leukemia-associated mutant Shp2 and Gab2, a scaffolding protein important for cytokine-induced PI3K/Akt signaling, was enhanced, and that the mTOR pathway was elevated in Ptpn11E76K/+ leukemic cells. Importantly, MPN induced by the Ptpn11E76K/+ mutation was markedly attenuated in Ptpn11E76K/+/Gab2-/- double mutant mice-overproduction of myeloid cells was alleviated, splenomegaly was diminished and myeloid cell infiltration in nonhematopoietic organs was decreased in these double mutants. Excessive myeloid differentiation of stem cells was also normalized by depletion of Gab2. Acute leukemia progression of MPN was reduced in the double mutant mice and, as such, their survival was much prolonged. Furthermore, treatment of Ptpn11E76K/+ mice with Rapamycin, a specific and potent mTOR inhibitor, mitigated MPN phenotypes. Collectively, this study reveals an important role of the Gab2/PI3K/mTOR pathway in mediating the pathogenic signaling of the PTPN11 gain-of-function mutations and a therapeutic potential of Rapamycin for PTPN11 mutation-associated JMML.