The Lyu Laboratory
Dongwen Lyu (Lv), PhD
Assistant Professor
Cellular Biology & Anatomy
Assistant Professor, Georgia Cancer Center (GCC)
Jump to: Research SummaryImpact on Georgia patientsResearch Focus Research InterestsPublicationsTeam
Contact Us
The Dongwen Lyu Lab
Health Sciences Campus
GCC - M. Bert Storey Research Building
1410 Laney-Walker Blvd., CN-3133A1
(706) 721-8268
Research Summary
The Lyu Lab focuses on investigating and modulating protein function, with particular interest in intrinsically disordered proteins, membrane proteins, protein folding, arginylation, and protein–protein interactions. We aim to develop small-molecule therapeutics, including covalent and non-covalent inhibitors, proteolysis-targeting chimeras (PROTACs), molecular glue degraders (MGDs), and other novel degraders and modulators, to target disease-associated proteins for the treatment of cancers and other diseases.
Impact on Patients in Georgia
Dr. Lyu is pioneering a transformative approach to cancer treatment: instead of trying to block disease-causing proteins with drugs, he is engineering molecular tools that physically destroy them—a strategy called targeted protein degradation.
By systematically expanding the range of proteins that can be eliminated this way, his lab is opening treatment possibilities for cancers that have long been considered 'undruggable,' including leukemias, breast, lung, and prostate cancers.
His platform technologies, already producing publications in top journals, represent a new generation of precision cancer medicine with broad applicability across Georgia's most prevalent cancers.
Research Projects
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Hijacking Arginylation for Targeted Protein Degradation
Protein arginylation, catalyzed by ATE1, is an important post-translational modification that regulates protein stability and is implicated in cancer progression. We aim to identify arginylated proteins and their modification sites in cancer cells and to harness ATE1 for targeted protein degradation through a novel strategy called Arginylation Targeting Chimera (ArgTAC). This work may establish a new therapeutic platform for targeting cancer-driving proteins.
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Drugging the Undruggable Proteome
Approximately 85% of the human proteome remains undruggable by conventional small-molecule approaches. Our lab develops innovative chemical biology platforms and targeted protein modulation strategies to expand the druggable proteome. We created polyHisTAC, a versatile tool to rapidly assess the degradability of challenging proteins and validate their suitability for PROTAC-based targeting. Using these platforms, we develop PROTACs, molecular glue degraders, and other targeted protein modulators to drug previously inaccessible disease-relevant proteins.
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Caspase Cleavage Targeting Chimeras (CACTACs)
Caspases are proteases that cleave proteins to regulate cell death and other cellular processes. We are developing Caspase Cleavage Targeting Chimeras (CACTACs), a new modality that induces targeted protein cleavage by recruiting caspases to disease-relevant proteins. This approach provides a distinct way to rapidly disable protein function and may lead to new cancer therapies.
- Chemical Biology of Protein Arginylation
The biological functions of protein arginylation remain poorly understood. We develop and apply chemical biology, proteomics, and functional genomics approaches to identify arginylation sites and substrates, uncover their roles in cardiovascular biology and disease, and discover enzymes involved in de-arginylation. These studies will advance our understanding of arginylation and enable new strategies for therapeutic intervention.
Recent Publications
- Chen, H.*, Zhu, D.*, Billitti, M., Sun, A., Jin, L., Moser, E., Mivechi, N.F., Zheng, G.**, Lv, D.** (2026) Development of polyHis-targeting PROTAC degraders. Angew. Chem. Int. Ed. 65(11):e22845 https://doi.org/10.1002/anie.202522845
- Wang, Z.*, Pan, B.S.*, Manne, R.K.*, Chen, J.*, Lv, D., Wang, M., Tran, P., Weldemichael, T.G., Yan, W., Shao, J., Hsu, C.C., Hromas, R., Zhou, D., Qin, Z.**, Lin, H.K.**, Li, H.Y.** (2025) CD36-mediated endocytosis of proteolysis-targeting chimeras. Cell 188, 1–19. https://doi.org/10.1016/j.cell.2025.03.036
- Xiao, Y., Yuan, Y., Liu, Y., Lin, Z., Zheng, G., Zhou, D., Lv, D.* (2024) Targeted protein degradation: current and emerging approaches to identify new E3 ligases. Journal of Medicinal Chemistry 67(14):11580–11596 https://doi.org/10.1021/acs.jmedchem.4c00723
- Nayak, D.*, Lv, D.*, Yuan, Y., Zhang, P., Hu, W., Ruben, E.A., Lv, Z., Sung, P., Hromas, R., Zheng, G.**, Zhou, D.** and Olsen, S.K.** (2024) Structure-guided development of a more potent second-generation dual degrader of BCL-2 and BCL-xL. Nature Communications 15:2743 https://doi.org/10.1038/s41467-024-46922-4
- Lin, Z., Garcia, B. Lv, D.* (2023) Bifunctional Peptide Nanofibrils for Targeted Protein Degradation. Angew. Chem. Int. Ed. https://doi.org/10.1002/anie.202316581
- Pei, J.*, Xiao, Y.*, Liu, X.*, Hu, W., Sobh A., Yuan, Y., Zhou S., Hua, N., Yang Y., Mackintosh, S.G., Zhang, X., Basso K.B., Kamat M., Yang, Q., Licht, J.D., Zheng, G.**, Zhou, D.**, Lv, D.** (2023) Piperlongumine conjugates induce targeted protein degradation. Cell Chemical Biology 30 (2), 203–213. https://doi.org/10.1016/j.chembiol.2023.01.004
- Lv, D.*, Pal, P.*, Liu, X., Jia, Y., Thummuri, D., Zhang, P., Hu, W., Pei, J., Zhang, Q., Zhou, S., Khan, S., Zhang, X., Hua, N., Yang, Q., Arango, S., Zhang, W., Nayak, D., Olsen, S.K., Weintraub, S.T., Hromas, R. Konopleva, M., Yuan, Y., Zheng, G., Zhou, D. (2021) A BCL-xL and BCL-2 dual degrader with improved anti-leukemic activity. Nature Communications 12, 6896. https://doi.org/10.1038/s41467-021-27210-x
- Khan, S.*, Zhang, X.*, Lv, D.*, Zhang, Q., He, Y., Zhang, P., Liu, X., Thummuri, D., Yuan, Y., Wiegand, J.S., Pei, J., Zhang, W., Sharma, A., McCurdy, C.R., Kuruvilla, V.M., Baran, N., Ferrando, A.A., Kim, Y., Rogojina, A., Houghton, P.J., Huang, G., Hromas, R.A., Konopleva, M.Y., Zheng G., Zhou, D. (2019) A selective BCL-XL PROTAC degrader achieves safe and potent antitumor activity. Nature Medicine 25, 1938–1947. https://doi.org/10.1038/s41591-019-0668-z
- Lv, D.-W., Zhang, K., Li, R. (2018) Interferon regulatory factor 8 regulates caspase-1 expression to facilitate Epstein-Barr virus reactivation in response to B cell receptor stimulation and chemical induction. PLOS Pathogens 14(1): e1006868. https://doi.org/10.1371/journal.ppat.1006868
Research Team
