Compared to occasional genomic mutations and horizontal gene transfer events, constant phenotypic variations and diversifications are intrinsic in bacteria. Such phenotypic diversity enables small portions of the bacterial population to survive, grow, and even expand amidst host immunity and antibiotic pressures, which could further drive the clinical evolution of this pathogen. Delving into the phenotypic heterogeneity of bacterial pathogens and its underlying molecular mechanisms provides insights into their behavioral patterns during infection and treatment, aiding in predicting their clinical evolutionary trajectories and uncovering overlooked drug targets. 

 

Our team employs high-throughput microscopy and single-bacterium sequencing techniques to systematically interrogate the phenotypic and gene expression landscape of key pathogens across varying conditions. We aim to track the cellular and populational dynamics of these pathogens upon transmission, infection establishment, antibiotic adaptation, and immune evasion. We also seek to identify bacterial subpopulations which are pivotal to disease development and treatment responses, as well as their molecular fingerprints. Such findings may offer valuable insights for refining clinical preventive, diagnostic, and therapeutic strategies.

B.S. 2007 Biology Peking University, School of Life Sciences
Ph.D. 2011 Cell Biology Peking University, School of Life Sciences

Postdoctoral Fellow Training
2017-2021 Dr. Eric J. Rubin’s lab Harvard T.H. Chan School of Public Health
Professional Appointments
2021-2023 Research Scientist Harvard T.H. Chan School of Public Health
2023-present Principal Investigator, Institute of Microbiology, Chinese Academy of Sciences (IMCAS)

1. Harim I. Won, Junhao Zhu^#*, Olga Kandror, Tatos Akopian, Ian D. Wolf, Michael C. Chao, Maya Waldor, Eric J. Rubin. Chemically induced targeted protein degradation in mycobacteria uncovers antibacterial effects and potentiates antibiotic efficacy. BioRxiv, 2023. 

2. Junhao Zhu, Yue J. Liu, Sarah M. Fortune. Spatiotemporal perspectives on tuberculosis chemotherapy. Current Opinion in Microbiology 2023, 72:102266. 

3. Qingyun Liu, Junhao Zhu^#, Charles L Dulberger, Sydney Stanley, Sean Wilson, Eun Seon Chung, Xin Wang, Peter Culviner, Yue J. Liu, Nathan D. Hicks, Gregory H. Babunovic, Samantha R. Giffen, Bree B. Aldridge, Ethan C. Garner, Eric J. Rubin, Michael C. Chao, Sarah M. Fortune. Tuberculosis treatment failure associated with evolution of antibiotic resilience. Science 2022, 378(6624):1111-1118. 

4. Junhao Zhu, Ian D. Wolf, Charles L. Dulberger, Harim I. Won, Jemila C. Kester, Julius A. Judd, Samantha E. Wirth, Ryan R. Clark, Yawei Li, Yuan Luo, Todd A Gray, Joseph T Wade, Keith M Derbyshire, *Sarah M Fortune, Eric J Rubin. Spatiotemporal localization of proteins in mycobacteria. Cell Reports 2021, 37(13):110154. 

5. Biwei Wang, Junhao Zhu^#, Babak Javid. Clinically relevant mutations in mycobacterial LepA cause rifampicin-specific phenotypic resistance. Scientific Reports 2020, 21;10(1):8402. 

6. Junhao Zhu^#, Biwei Wang, Miaomiao Pan, Yuna Zeng, Hesper Rego, Babak Javid. Rifampicin can induce antibiotic tolerance in mycobacteria via paradoxical changes in rpoB transcription. Nature Communications 2018, 9(1):4218. 

7. Hongwei Su, Junhao Zhu^#, Hao Li, Rongjun Cai, Christopher Ealand, Xun Wang, Yuxiang Chen, Masood Ur Rehman Kayani, Ting F. Zhu, Danesh Moradigaravand, Hairong Huang, Bavesh D Kana, Babak Javid. The essential mycobacterial amidotransferase GatCAB is a modulator of specific translational fidelity. Nature Microbiology 2016, 1(11):16147. 

8. Chidiebere Akusobi, Bouchra S Benghomari, Junhao Zhu, Ian D Wolf, Shreya Singhvi, Charles L Dulberger, Thomas R Ioerger, *Eric J Rubin. Transposon mutagenesis in Mycobacterium abscessus identifies an essential penicillin-binding protein involved in septal peptidoglycan synthesis and antibiotic sensitivity. Elife 2022, 11:e71947. 

9. Yiwei Zhang, Junhao Zhu, Zhengqi Wang, You Wu, Xianbin Meng, Xuhui Zheng, Babak Javid. HspX promotes the polar localization of mycobacterial protein aggregates. Scientific Reports 2019, 9(1):14571.