Browsing by Author "Mo, Qianxing"

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    Chronic Infection Depletes Hematopoietic Stem Cells through Stress-Induced Terminal Differentiation
    (Cell Press, 2016) Matatall, Katie A.; Jeong, Mira; Chen, Siyi; Sun, Deqiang; Chen, Fengju; Mo, Qianxing; Kimmel, Marek; King, Katherine Y.
    Chronic infections affect a third of the world’s population and can cause bone marrow suppression, a severe condition that increases mortality from infection. To uncover the basis for infection-associated bone marrow suppression, we conducted repeated infection of WT mice with Mycobacterium avium. After 4–6 months, mice became pancytopenic. Their hematopoietic stem and progenitor cells (HSPCs) were severely depleted and displayed interferon gamma (IFN-γ) signaling-dependent defects in self-renewal. There was no evidence of increased HSPC mobilization or apoptosis. However, consistent with known effects of IFN-γ, transcriptome analysis pointed toward increased myeloid differentiation of HSPCs and revealed the transcription factor Batf2 as a potential mediator of IFN-γ-induced HSPC differentiation. Gain- and loss-of-function studies uncovered a role for Batf2 in myeloid differentiation in both murine and human systems. We thus demonstrate that chronic infection can deplete HSPCs and identify BATF2 as a mediator of infection-induced HSPC terminal differentiation.
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    Collagen-rich airway smooth muscle cells are a metastatic niche for tumor colonization in the lung
    (Springer Nature, 2019) Lee, Yu-Cheng; Kurtova, Antonina V.; Xiao, Jing; Nikolos, Fotis; Hayashi, Kazukuni; Tramel, Zoe; Jain, Antrix; Chen, Fengju; Chokshi, Mithil; Lee, Ciaran; Bao, Gang; Zhang, Xiang; Shen, Jianjun; Mo, Qianxing; Jung, Sung Yun; Rowley, David; Chan, Keith Syson; Bioengineering
    Metastases account for the majority of cancer deaths. While certain steps of the metastatic cascade are well characterized, identification of targets to block this process remains a challenge. Host factors determining metastatic colonization to secondary organs are particularly important for exploration, as those might be shared among different cancer types. Here, we showed that bladder tumor cells expressing the collagen receptor, CD167a, responded to collagen I stimulation at the primary tumor to promote local invasion and utilized the same receptor to preferentially colonize at airway smooth muscle cells (ASMCs)—a rich source of collagen III in lung. Morphologically, COL3-CD167a-driven metastatic foci are uniquely distinct from typical lung alveolar metastatic lesions and exhibited activation of the CD167a-HSP90-Stat3 axis. Importantly, metastatic lung colonization could be abrogated using an investigational drug that attenuates Stat3 activity, implicating this seed-and-soil interaction as a therapeutic target for eliminating lung metastasis.
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    Collagen-rich airway smooth muscle cells are a metastatic niche for tumor colonization in the lung
    (Springer Nature, 2019) Lee, Yu-Cheng; Kurtova, Antonina V.; Xiao, Jing; Nikolos, Fotis; Hayashi, Kazukuni; Tramel, Zoe; Jain, Antrix; Chen, Fengju; Chokshi, Mithil; Lee, Ciaran; Bao, Gang; Zhang, Xiang; Shen, Jianjun; Mo, Qianxing; Jung, Sung Yun; Rowley, David; Chan, Keith Syson; Bioengineering
    Metastases account for the majority of cancer deaths. While certain steps of the metastatic cascade are well characterized, identification of targets to block this process remains a challenge. Host factors determining metastatic colonization to secondary organs are particularly important for exploration, as those might be shared among different cancer types. Here, we showed that bladder tumor cells expressing the collagen receptor, CD167a, responded to collagen I stimulation at the primary tumor to promote local invasion and utilized the same receptor to preferentially colonize at airway smooth muscle cells (ASMCs)—a rich source of collagen III in lung. Morphologically, COL3-CD167a-driven metastatic foci are uniquely distinct from typical lung alveolar metastatic lesions and exhibited activation of the CD167a-HSP90-Stat3 axis. Importantly, metastatic lung colonization could be abrogated using an investigational drug that attenuates Stat3 activity, implicating this seed-and-soil interaction as a therapeutic target for eliminating lung metastasis.