Wang. Dong - University of California, San Diego - Skaggs School of Pharmacy and Pharmaceutical Sciences

个人简介

Dr. Dong Wang obtained his B.S. at Peking University and Ph.D. with Dr. Stephen Lippard at MIT. His role in Lippard group was to investigate the effect of nucleosome structure and epigenetic status change on DNA repair of platinum DNA damage. Dr. Wang then joined Dr. Roger Kornberg’s group at Stanford University as a postdoc fellow. His postdoc research focused on understanding the molecular mechanism of Pol II transcription elongation and fidelity.

研究领域

MOLECULAR MECHANISMS OF DNA DAMAGE PROCESSING PATHWAYS Our DNA blueprint is under continuous attack by both normal metabolic activities and environmental agents, resulting in as many as tens of thousands of individual DNA lesions per cell per day. These lesions can block replication and transcription processes and trigger a variety of DNA damage processing pathways, including DNA repair and checkpoints that result in cell cycle arrest and apoptosis. Defects in these DNA damage processing pathways lead to genome instability and many human diseases, such as cancer and neurodegenerative disorders. Dr. Wang's research focuses on understanding the mechanisms of cellular responses to DNA damage, particularly the functional interplay between transcription and epigenetic DNA modifications and lesions. His group takes a multidisciplinary approach, combining structural biology, chemical biology, computational biology, biochemical, and genetic methods, to study key protein complexes involved in these processing pathways. The results will have implications for DNA damage recognition and DNA repair. Moreover, understanding how cell process these DNA lesions will help us to decipher the mechanisms of drug action and resistance and pave the way for rational improvement of novel anticancer drugs.

近期论文

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Aiyer, S., Baldwin, P. R., Tan, S. M., Shan, Z., Oh, J., Mehrani, A., Bowman, M. E., Louie, G., Passos, D. O., Đorđević-Marquardt, S., Mietzsch, M., Hull, J. A., Hoshika, S., Barad, B. A., Grotjahn, D. A., McKenna, R., Agbandje-McKenna, M., Benner, S. A., Noel, J. A. P., Wang, D., Tan, Y. Z., Lyumkis, D. (2024) Overcoming resolution attenuation during tilted cryo-EM data collection. Nat. Commun. 15, 389. Saram, R. D., Xu, J., Lahiri, I., Gong, W., Li, Q., Oh, J., Zhou, Z., Hou, P., Chong, J., Hao, N., Li, S.*, Wang, D.*, Leschziner, A. E*. (2024) Elf1 promotes Rad26's interaction with lesion-arrested Pol II for transcription-coupled repair. Proc . Natl. Acad. Sci. USA. 121 (3), e2314245121. Oh, J., Shan, Z., Hoshika, S., Xu, J., Chong, J., Benner, S. A.*, Lyumkis, D.*, Wang, D.* (2023) A Unified Watson-Crick Geometry Drives Transcription of Six-Letter Expanded DNA Alphabets by E. coli RNA Polymerase. Nat. Commun. 14:8219. Oh, J., Kimoto, M., Xu, H., Chong, J, Hirao, I*, Wang, D.* (2023) Structural basis of transcription recognition of a hydrophobic unnatural base pair by T7 RNA polymerase. Nat. Commun. 14:195. Unarta, I. C., Goonetilleke, E. C., Wang, D., Huang, X. H. (2023) Nucleotide Addition and Cleavage by RNA Polymerase II: Coordination of Two Catalytic Reactions using a Single Active Site. J. Biol. Chem. DOI: https://doi.org/10.1016/j.jbc.2022.102844 Yan, W., Cao, M., Ruan, X., Jiang, L., Lee, S., Lemanek, A., Ghassemian, M., Pizzo, D.P., Wan, Y., Qiao, Y., Chin, A.R., Duggan, E., Wang, D., Nolan, J.P., Esko, J.D., Schenk, S.* & Wang, S.E.* (2022) Cancer-cell-secreted miR-122 suppresses O-GlcNAcylation to promote skeletal muscle proteolysis. Nat. Cell Biol. 24, 793-804. Fei, J., Xu, J., Li, Z., Xu, K., Wang, D., Kassavetis, G.A. & Kadonaga, J.T. (2022) NDF is a transcription factor that stimulates elongation by RNA polymerase II. Genes Dev. 36, 294-299. Oh, J., Jia, T., Xu, J., Chong, J., Dervan, P.B.* & Wang, D.* (2022) RNA polymerase II trapped on a molecular treadmill: structural basis of persistent transcriptional arrest by a minor groove DNA binder. Proc. Natl. Acad. Sci. USA. 119 (3), e2114065119. Yan, C., Dodd, T., Yu, J., Leung, B., Xu, J., Oh, J., Wang, D.* & Ivanov, I. * (2021) Mechanism of Rad26-assisted rescue of stalled RNA polymerase II in transcription-coupled repair. Nat. Commun. 12:7001. Xu, J., Oh, J., Chong, J., Xu, L., & Wang, D.* (2021) Molecular Basis for Transcriptional Fidelity Control by RNA polymerase II. In R. Landick, J.D. Wang, & T. Strick (Eds) RNA Polymerases as Molecular Motors. 2nd Ed. Royal Society of Chemistry Press. Xu, J., Chong, J. & Wang, D.* (2021) Strand-specific effect of Rad26 and TFIIS in rescuing transcriptional arrest by CAG trinucleotide repeat slip-outs. Nucleic Acids Res. doi: 10.1093/nar/gkab573. Oh, J., Shin, J., Unarta, I.C., Wang, W., Feldman, A.W., Karadeema, R.J., Xu, L., Xu, J., Chong, J., Krishnamurthy, R., Huang, X., Romesberg, F.E. & Wang, D.* (2021) Transcriptional processing of an unnatural base pair by eukaryotic RNA polymerase II. Nat. Chem. Biol. doi: 10.1038/s41589-021-00817-3. Konovalov, K.A., Wang, W., Wang, G., Gao, X., Wang, D. & Huang, X.* (2021) A comprehensive mechanism for 5-carboxylcytosine-induced transcriptional pausing revealed by Markov state models. J. Biol. Chem. doi: 10.1016/j.jbc.2021.100735. Xu, J., Chong, J. & Wang, D.* (2021) Opposite roles of transcription elongation factors Spt4/5 and Elf1 on RNA polymerase II transcription through B-form versus non-B DNA structures. Nucleic Acids Res. doi: 10.1093/nar/gkab240. Yuan, S., Yin, X., Meng, X., Chan, J.F.-W., Ye, Z.-W., Riva, L., Pache, L., Chan, C.C.-Y., Lai, P.M., Chan, C..C.-S., Poon, V.K.-M., Lee, A.C.-Y., Matsunaga, N., Pu, Y., Yuen, C.-K., Cao, J., Liang, R., Tang, K., Sheng, L., Du, Y., Xu, W., Lau, C.-Y., Sit, K.-Y., Au, W.-K., Wang, R., Zhang, Y.-Y., Tang, Y.-D., Clausen, T.M., Pihl, J., Oh, J., Sze, K.-H., Zhang, A.J., Chu, H., Kok, K.-H., Wang, D., Cai, X.-H., Esko, J.D., Hung, I.F.-N., Li, R.A., Chen, H., Sun, H., Jin, D.-Y., Sun, R.*, Chanda, S.K.* & Yuen, K.Y.* (2021) Clofazimine broadly inhibits coronaviruses including SARS-CoV-2. Nature. doi: 10.1038/s41586-021-03431-4. Milanovic, M., Shao, Z., Estes, V.M., Wang, X.S., Menolfi, D., Lin, X., Lee, B.J., Xu, J., Cupo, O.M., Wang, D. & Zha, S. (2021) FATC Domain Deletion Compromises ATM Protein Stability, Lymphocyte Development, and Promotes Lymphomagenesis. J. Immun. 206(6):1228-1239. Oh, J., Xu, J.,, Chong, J. & Wang, D.* (2021) Molecular Basis of Transcriptional Pausing, Stalling, and Transcription-coupled Repair Initiation. Biochim. Biophys. Acta. Gene Regul. Mech. 1864(1):194659. Milanovic, M., Sprinzen, L., Lee, J.H., Yamamoto, K., Li, Y., Lee, B.J., Xu, J., Estes, V.E., Wang, D., Mckinnon, P.J., Paull, T. & Zha, S. (2021) The Cancer-Associated ATM R3008H Mutation Reveals the Link between ATM activation and Its Exchange. Cancer Res. 81(2): 426-437. Wang, D.* (2020) Using Genetics to Reveal Protein Structure. Science. 370(6522): 1269-1270. Xu, J., Wang, W., Xu, L., Chen, J.Y., Chong, J., Oh, J., Leschziner, A.E., Fu, X.D. & Wang, D.* (2020) Cockayne Syndrome B Protein Acts as an ATP-Dependent Processivity Factor that Helps RNA Polymerase II Overcome Nucleosome Barriers. Proc. Natl. Acad. Sci. USA. doi: 10.1073/pnas.2013379117. Wang, D.* (2020) A Panorama of Transcription-Coupled Repair in Yeast Chromatin. Proc. Natl. Acad. Sci. USA. doi:10.1073/pnas.2014392117. Oh., J., Fleming, A.M., Xu, J., Chong, J., Burrows, C.J. & Wang, D.* (2020) RNA Polymerase II Stalls on Oxidative DNA Damage via a "Torsion-Latch" Mechanism Involving Lone Pair-Pi and CH-Pi Interactions. Proc. Natl. Acad. Sci. USA. 117(17): 9338-9348. PMCID: PMC7196775. Di, L., Fu, Y., Sun, Y., Li, J., Liu, L., Yao, J., Wang, G., Wu, Y., Lao, K., Lee, R.W., Zheng, G., Xu, J., Oh, J., Wang, D., Xie, X.S., Huang, Y. & Wang J. (2020) RNA Sequencing by Direct Tagmentation of RNA/DNA Hybrids. Proc. Natl. Acad. Sci. USA. 117(6):2886-2893. PMCID: PMC7022195.