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Li Wu, PhD

Professor, Endowed Chair and Department Executive Officer

Introduction

Dr. Wu’s lab aims to uncover the mechanisms underlying viral replication and host immune responses, essential steps in developing targeted antiviral therapies. By studying HIV-1 and SARS-CoV-2 replication, virus-host interactions, and innate antiviral immunity, the lab seeks to elucidate the complex processes driving viral infections. One key area of focus is how N6-methyladenosine (m6A) RNA modifications regulate both viral and cellular gene expression, influencing the host’s response to infection. Additionally, the lab investigates the role of SAMHD1, a unique cellular enzyme that regulates dNTP levels and genomic stability, in restricting viral replication and modulating immune responses. Together, these insights form a critical foundation for the development of innovative antiviral strategies.

Current research projects in the lab include:

1. Targeting HIV-1 RNA modifications in latently infected CD4+ T cells for therapeutic development.

2. Exploring m6A RNA modification in HIV-associated cancers in aging populations.

3. HIV-1-induced upregulation of m6A modifications of cellular RNA in CD4+ T-cells.

4. SAMHD1-mediated regulation of HIV-1 innate immunity and viral gene expression.

5. SAMHD1-mediated regulation of innate immunity during SARS-CoV-2 infection.

Current Positions

  • Professor of Microbiology and Immunology
  • Chair and Department Executive Officer, Microbiology and Immunology
  • Microbiology Endowed Chair

Education

  • PhD in Molecular Virology, Shanghai Medical College (formerly Shanghai Medical University), Fudan University, Shanghai, China
  • Postdoctoral Research Fellow, HIV Dynamics and Replication Program, National Cancer Institute, National Institutes of Health, Frederick, Maryland

Graduate Program Affiliations

Center, Program and Institute Affiliations

Research Interests

  • Molecular biology of HIV, SARS-CoV-2, and virus-host interactions
  • Functions and mechanisms of RNA modifications in viral infection
  • Molecular mechanisms of antiviral innate immunity

Licenses & Certifications

  • Elected Fellow of the American Academy of Microbiology (AAM)
  • Elected Fellow of the American Association for the Advancement of Science (AAAS)

Selected Publications

  • Mishra, T., Phillips, S., Zhao, Y., Wilms, B., He, C. & Wu, L. (2024). Epitranscriptomic m6A modifications during reactivation of HIV-1 latency in CD4+ T cells. mBio 15(11):e0221424. doi: 10.1128/mbio.02214-24. PMID: 39373537.
  • Baek, A., Lee, G. E., Golconda, S., Rayhan, A., Manganaris, A. A., Chen, S., Tirumuru, N., Yu, H., Kim, S., Kimmel, C., Zablocki, O., Sullivan, M. B., Addepalli, B., Wu, L. & Kim, S. (2024). Single-molecule epitranscriptomic analysis of full-length HIV-1 RNAs reveals functional roles of site-specific m6As. Nat Microbiol 9(5):1340-1355. DOI: 10.1038/s41564-024-01638-5. PMID: 38605174.
  • Phillips, S., Mishra, T., Huang, S. & Wu, L. (2024). Functional impacts of epitranscriptomic m6A modification on HIV-1 infection. Viruses 16 (1):127. DOI: 10.3390/v16010127. PMID: 38257827.
  • Espada, C.E., Sari, L., Cahill, M.P., Yang, H,. Phillips, S., Martinez, N., Kenney, A.D., Yount, J.S., Xiong, Y., Lin, M.M. & Wu, L. (2023). SAMHD1 impairs type I interferon induction through the MAVS, IKKε, and IRF7 signaling axis during viral infection.  J Biol Chem 299(7):104925. DOI: 10.1016/j.jbc.2023.104925. PMID: 37328105.
  • Yang, H., Espada, C.E., Phillips, S., Martinez, N., Kenney, A.D., Yount, J.S., Xiong, Y. & Wu, L. (2023). The host anti-viral protein SAMHD1 suppresses NF-κB activation by interacting with the IKK complex during inflammatory responses and viral infection. J Biol Chem 299(6):104750. DOI: 10.1016/j.jbc.2023.104750. PMID: 37100289.
  • Chen, S., Kumar, S., Espada, C. E., Tirumuru, N., Cahill, M. P., Hu, L., He, C. & Wu, L. (2021). N6-methyladenosine modification of HIV-1 RNA suppresses type-I interferon induction in differentiated monocytic cells and primary macrophages. PLoS Pathog 17(3):e1009421. DOI: 10.1371/journal.ppat.1009421. PMID: 33690734.
  • Espada, C. E., St Gelais, C., Bonifati, S., Maksimova, V. V., Cahill, M. P., Kim, S. H. & Wu, L. (2021). TRAF6 and TAK1 contribute to SAMHD1-mediated negative regulation of NF-kB signaling. J Virol 95(3):e01970-20. DOI: 10.1128/JVI.01970-20. PMID: 33177202.
  • Tirumuru, N. & Wu, L. (2019). HIV-1 envelope proteins up-regulate N6-methyladenosine levels of cellular RNA independently of viral replication. J Biol Chem 294(9):3249-3260. DOI: 10.1074/jbc.RA118.005608. PMID: 30617182.
  • Lu, W., Tirumuru, N., St Gelais, C., Koneru, P. C., Liu, C., Kvaratskhelia, M., He, C. & Wu, L. (2018). N6-methyladenosine-binding proteins suppress HIV-1 infectivity and viral production. J Biol Chem 293(34):12992-13005. DOI: 10.1074/jbc.RA118.004215. PMID: 29976753.
  • Chen, S., Bonifati, S., Qin, Z., St Gelais, C., Kodigepalli, K. M., Barrett, B. S., Kim, S. H., Antonucci, J. M., Ladner, K. J., Buzovetsky, O., Knecht, K. M., Xiong, Y., Yount, J. S., Guttridge, D. C., Santiago, M. L. & Wu, L. (2018). SAMHD1 suppresses innate immune responses to viral infections and inflammatory stimuli by inhibiting the NF-kB and interferon pathways. Proc Natl Acad Sci U S A 115(16):E3798-E3807. DOI: 10.1073/pnas.1801213115. PMID: 29610295.