Orchestrating the appropriate transcriptional output in response to changing environments is crucial for bacterial survival. However, achieving a detailed characterization of the regulatory mechanisms of gene expression in bacteria remains challenging. In previous work, we developed SEnd-seq (simultaneous 5' and 3' end sequencing), a method for full-length RNA profiling in bacteria, which enables transcriptome mapping with unprecedented resolution. This approach has provided new insights into transcriptional mechanisms and different paradigms of gene expression regulation across various bacterial species, including the widespread transcriptional pausing observed in Mycobacterium tuberculosis (Mtb).

Building on our previous findings, our lab focuses on investigating gene expression regulation, as well as its role in drug tolerance and resistance in Mtb, with the following research directions:

I. Deciphering the regulatory mechanisms, physiological roles, and potential drug targets associated with Mtb-specific gene expression features, such as pervasive transcriptional pausing and strict transcription-translation coupling.

II. Exploring the molecular mechanisms and transcriptomic changes underlying Mtb's antibiotic tolerance and resistance, while developing novel transcriptome-based assays for drug sensitivity testing.

III. Profiling the transcriptomes of various pathogenic bacteria using SEnd-seq, focusing on comparing the transcriptional profiles of infected versus non-infected states.

Selected publications

First-author publications ( ^§equal contribution):

1. Ju X, Li S, Froom R, Wang L, Lilic M, Campbell E, Rock J, Liu S. Incomplete transcripts dominate the Mycobacterium tuberculosis transcriptome. Nature. 627, 424–430 (2024).

2. Ju X, Li D, Liu S. Full-length RNA profiling reveals pervasive bidirectional transcription terminators in bacteria. Nat Microbiol. 2019 Nov;4(11):1907-1918.

3. Li S^§, Ju X^§, Liu Q, Yan Y, Zhang C, Qin Y, Deng X, Li C, Tian M, Jin N, Jinag C. Ambient atmospheric PM worsens mouse lung injury induced by influenza A virus through lysosomal dysfunction. Respir Res. 2023 Dec 6;24(1):306.

4. Ju X^§, Yan Y^§, Liu Q, Li N, Sheng M, Zhang L, Li X, Liang Z, Huang F, Liu K, Zhao Y, Zhang Y, Zou Z, Du J, Zhong Y, Zhou H, Yang P, Lu H, Tian M, Li D, Zhang J, Jin N, Jiang C. Neuraminidaseof influenza A virus binds LAMPs directly and induces lysosome rupture. J Virol. 2015 Oct; 89(20):10347-58.

5. Xu C^§, Ju X^§, Song D^§, Huang F^§, Tang D, Zou Z, Zhang C, Joshi T, Jia L, Xu W, Xu K-F, Wang Q, Xiong Y, Guo Z, Chen X, Huang F, Xu J, Zhong Y, Zhu Y, Peng Y, Wang L, Zhang X, Jiang R, Li D, Jiang T, Xu D, Jiang C. An association analysis between psychophysical characteristics and genome-wide gene expression changes in human adaptation to the extreme climate at the Antarctic Dome Argus. Mol Psychiatry. 2015 Apr; 20(4):536-44.

Other publications:

1. Wang L, Watters JW, Ju X, Lu G, Liu S. Head-on and co-directional RNA polymerase collisions orchestrate bidirectional transcription termination. Mol Cell. 2023 Apr 6;83(7):1153-1164.e4.

2. Zhao Y, Huang F, Zou Z, Bi Y, Yang Y, Zhang C, Liu Q, Shang D, Yan Y, Ju X, Mei S, Xie P, Li X, Tian M, Tan S, Lu H, Han Z, Liu K, Zhang Y, Liang J, Liang Z, Zhang Q, Chang J, Liu WJ, Feng C, Li T, Zhang MQ, Wang X, Gao GF, Liu Y, Jin N, Jiang C. Avian influenza viruses suppress innate immunity by inducing trans-transcriptional readthrough via SSU72. Cell Mol Immunol. 2022 Jun;19(6):702-714.

3. Dong P, Ju X, Yan Y, Zhang S, Cai M, Wang H, Chen H, Hu Y, Cui L, Zhang J, He W. γδ T Cells Provide Protective Function in Highly Pathogenic Avian H5N1 Influenza A Virus Infection. Front Immunol. 2018 Dec 4;9:2812.

4. Zhang J, Qin X, Wang B, Xu G, Qin Z, Wang J, Wu L, Ju X, Bose DD, Qiu F, Zhou H, Zou Z. Zinc oxide nanoparticles harness autophagy to induce cell death in lung epithelial cells. Cell Death Dis. 2017 Jul 27;8(7):e2954.

5. Sheng M, Zhong Y, Chen Y, Du J, Ju X, Zhao C, Zhang G, Zhang L, Liu K, Yang N, Xie P, Li D, Zhang MQ, Jiang C. Hsa-miR-1246, hsa-miR-320a and hsa-miR-196b-5p inhibitors can reduce the cytotoxicity of Ebola virus glycoprotein in vitro. Sci China Life Sci. 2014 Oct;57(10):959-72.

6. Zou Z, Yan Y, Shu Y, Gao R, Sun Y, Li X, Ju X, Liang Z, Liu Q, Zhao Y, Guo F, Bai T, Han Z, Zhu J, Zhou H, Huang F, Li C, Lu H, Li N, Li D, Jin N, Penninger JM, Jiang C. Angiotensin-converting enzyme 2 protects from lethal avian influenza A H5N1 infections. Nat Commun. 2014 May 6;5:3594.

7. Yang N, Ma P, Lang J, Zhang Y, Deng J, Ju X, Zhang G, Jiang C. Phosphatidylinositol 4-kinase IIIβ is required for severe acute respiratory syndrome coronavirus spike-mediated cell entry. J Biol Chem. 2012 Mar 9;287(11):8457-67.

8. Li C, Yang P, Sun Y, Li T, Wang C, Wang Z, Zou Z, Yan Y, Wang W, Wang C, Chen Z, Xing L, Tang C, Ju X, Guo F, Deng J, Zhao Y, Yang P, Tang J, Wang H, Zhao Z, Yin Z, Cao B, Wang X, Jiang C. IL-17 response mediates acute lung injury induced by the 2009 pandemic influenza A (H1N1) virus. Cell Res. 2012 Mar;22(3):528-38.

9. Sun Y, Li C, Shu Y, Ju X, Zou Z, Wang H, Rao S, Guo F, Liu H, Nan W, Zhao Y, Yan Y, Tang J, Zhao C, Yang P, Liu K, Wang S, Lu H, Li X, Tan L, Gao R, Song J, Gao X, Tian X, Qin Y, Xu KF, Li D, Jin N, Jiang C. Inhibition of autophagy ameliorates acute lung injury caused by avian influenza A H5N1 infection. Sci Signal. 2012 Feb 21;5(212):ra16.