The Lyu Lab
Dongwen Lyu (Lv), PhD
Assistant Professor, Cellular Biology & Anatomy
Assistant Professor, Georgia Cancer Center (GCC)
Primary Area of Interest
We focus on developing small-molecule degraders and modulators to target disease-associated proteins for the treatment of cancer and other diseases.
Jump to: Research Summary Research Interests Selected Publications Research Team
Contact Us
The Dongwen Lyu Lab
Health Sciences Campus
GCC - M. Bert Storey Research Building
1410 Laney-Walker Blvd., CN-3133A3
(706) 721-8268
Research Summary
The Lyu Lab focuses on two broad research areas. The first centers on investigating and modulating protein function, with emphasis on protein folding and dynamics, protein arginylation, protein–protein interactions, membrane proteins, and intrinsically disordered proteins. 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. The second research area focuses on elucidating the cellular and molecular mechanisms of aging and age-related diseases, particularly alternative splicing, protein isoforms, and protein quality control. Our goal is to discover and develop senolytic drugs that selectively eliminate senescent cells, offering new therapeutic strategies for aging-associated diseases.
Research Interests/Current Projects
- Cancer Diseases of Interest
Leukemia, Lung cancer, & Prostate cancer - Other Diseases of Interest
Vascular diseases, Autoimmune disorders, & Neurodegenerative diseases
- Research Methodologies
Pooled & arrayed CRISPR knockout/activation screen, CRISPR-based gene editing, high-throughput drug screening, PROTAC, Molecular Glue, Proteomics, Long-reads RNA-sequencing, Proximity labeling assays, & HiBiT/nanoBRET assay.
Project 1:
Title: Development of Caspase Cleavage Targeting Chimeras (CACTACs) for Targeted Protein Cleavage
Major Goals: We propose a novel approach called caspase cleavage targeting chimera (CACTAC) for targeted protein cleavage by recruiting caspases. Protein function can be abruptly stopped by the one-step, CACTAC-induced protein cleavage. CACTACs that target oncoproteins could be developed as potential cancer therapies.
Project Number: R21CA286307
Source of Support: NIH/NCI
Project 2:
Title: Hijacking Post-translational Arginylation for Targeted Protein Degradation
Major Goals: Unbiased identification of arginylation sites is critical for understanding their functions in cancers. Success in the proposed studies would represent a breakthrough in both protein arginylation and targeted protein degradation fields. ArgTACs that potentially target any oncoproteins could be developed into novel cancer therapies.
Project Number: R21CA292191
Source of Support: NIH/NCI
Project 3:
Title: Development and Application of Chemical Biology Approaches for Understanding Protein Arginylation
Major Goals: To understand the relationship between arginylation functions and cardiovascular disease by revealing arginylation prevalence in cardiac proteomes, arginylation involvement in epigenetics, cardiac development, and protein degradation.
Project Number: R01HL177113
Source of Support: NIH/NHLBI
Selected Publications
- 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
- 2. 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 l Journal of Medicinal Chemistry 67(14):11580–11596 https://doi.org/10.1021/acs.jmedchem.4c00723
- 3. 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
- 5. Pei, J.*, Xiao,*, 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
- 6. 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
- 7. 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– https://doi.org/10.1038/s41591-019-0668-z
- 8. 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
Xiaoguo Zhang
Dong Zhu, PhD
- Postdoctoral Fellow