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.

Dongwen Lyu, PhD

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-3133A1, Augusta, GA

(706) 721-8268

dlyu@augusta.edu

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

Dong Zhu, PhD

Postdoctoral Fellow

Reduce the Burden

The Georgia Cancer Center at Augusta University is dedicated to reducing the burden of cancer in Georgia and across the globe through superior care, innovation, and education. Through unprecedented expansion, the Georgia Cancer Center is providing access to more first-in-the-nation clinical trials, world-renowned experts and life-saving options.