Yilun Sun, PhD

Capital Medical University, BSc, Pharmaceutical Sciences, 2010

Georgetown University, MSc, Biotechnology, 2012

University of Illinois at Chicago, PhD, Biopharmaceutical Sciences, 2017

National Cancer Institute, NIH, Postdoctoral Fellow, Molecular Pharmacology, 2020

National Cancer Institute, NIH, Research Fellow, Molecular Pharmacology, 2024

Dr. Yilun Sun received his Ph.D. degree in Biopharmaceutical Sciences from University of Illinois College of Pharmacy in 2017. He joined National Cancer Institute (NCI), NIH in 2018 as a Postdoctoral Fellow and then Research Fellow in 2021, where he studied topoisomerases, poly(ADP-ribose) polymerases (PARP), DNA repair, and their cancer relevance.

Topoisomerase inhibitors (topotecan, irinotecan, etoposide, and doxorubicin) and PARP inhibitors (olaparib, rucaparib, and talazoparib) are widely used in cancer chemotherapy as DNA-damaging agents and are in clinical development for tumor-targeted delivery approaches (antibody-drug conjugates, nanoparticles, etc.). Dr. Sun and his lab investigate molecular mechanisms that repair DNA damage induced by topoisomerase inhibitors and PARP inhibitors in preclinical cancer models, lung cancer, colorectal cancer, and breast cancer in particular. He has developed immuno-biochemical assays and a single-molecule fluorescence method to interrogate mechanisms by which cancer cells resolve topoisomerase DNA-protein crosslinks (TOP-DPCs) and PARP-DNA complexes, whose induction by their respective inhibitors is the primary therapeutic mechanism of the drugs. He has delineated several post-translational modification-regulated pathways that resolve TOP-DPCs and PARP-DNA complexes, including those regulated by ubiquitylation, SUMOylation, neddylation, and ADP-ribosylation. He also interrogates proteases and nucleases that resolve non-specific DNA-protein crosslinks, such as those induced by reactive aldehydes. His research aims to identify and target novel DNA repair mechanisms to improve tumor response to topoisomerase inhibitors and PARP inhibitors. In addition, Dr. Sun and his lab investigate combinations of chemotherapies and immunotherapies in different cancer models. Dr. Sun also studies topoisomerase biology by conducting genome-wide CRISPR screening to identify and characterize genes/mechanisms that compensate for the loss of topoisomerases in human cells.

For more information: https://yilunsunlab.org/ 

Topoisomerases, PARP, chemotherapies, DNA repair, ubiquitin-like modifications

Yilun Sun*, Lisa M. Jenkins, Lara H. El Touny, Ukhyun Jo, Xi Yang, Liton Kumar Saha, Sourav Saha, Shunichi Takeda, Anthony K.L. Leung, Ken Cheng, Yves Pommier. Flap endonuclease 1 repairs DNA-protein cross-links via ADP-ribosylation-dependent mechanisms. Science Advances. 2025 Jan 10;11(2):eads2919. * Corresponding Author.

Huimin Zhang^#, Yun Xiong^#, Yilun Sun^#, Jeong-Min Park, Dan Su, Xu Feng, Mengfan Tang, Min Huang, Chao Wang, Mrinal Srivastava, Zhen Chen, Siting Li, Ling Yin, Yves Pommier, Junjie Chen. RAD54L2-mediated DNA damage avoidance pathway preserves genome integrity in response to topoisomerase 2 poisons. Science Advances. 2023 Dec 8;9(49):eadi6681. # Co-first author.

Yilun Sun*, Jiji Chen, Yves Pommier*. Real-time imaging of drug-induced trapping of cellular topoisomerases and poly(ADP-ribose) polymerases 1 at the single-molecule Nucleic Acids Research. 2023 Sep 6;gkad735. 

Yilun Sun. Quantitative Detection of DNA-Protein Crosslinks and Their Post-translational Modifications. Journal of Visualized Experiments. 2023 Apr 21;(194).

Yilun Sun*, Simone A. Baechler, Xiaohu Zhang, Suresh Kumar, Valentina Factor, Arakawa Yasuhiro, Kanako Okamoto, Anup Parikh, Yijun P. Su, Jiji Chen, Shar-yin N. Huang, Tabitha Ting, Shar-yin N Huang, Erin Beck, Zina Itkin, Crystal McKnight, Deepak Nijhawan, Changqing Xie, Nitin Roper, James Yang, Craig, J. Thomas, Yves Pommier*. Targeting neddylation sensitizes colorectal cancer to topoisomerase I Inhibitors by inactivating the DCAF13-CRL4 ubiquitin ligase complex. Nature Communications. 2023 Jun 23;14(1):3762.

Yilun Sun, John Nitiss, Yves Pommier. Editorial: The repair of DNA-protein crosslinks. Frontiers in Molecular Biosciences. 2023 Apr 28;10:1203479.

Yilun Sun*, Eroica Soans, Margarita Mishina, Elena Petricci, Karin C. Nitiss and John L. Nitiss*. Requirements for MRE11 endonuclease processing of topoisomerase II-mediated DNA damage in mammalian cell. Frontiers in Molecular Biosciences. 2022. 9:1007064.

Yilun Sun*, John L. Nitiss, Yves Pommier. SUMO: A Swiss Army Knife for Eukaryotic Topoisomerases. Frontiers in Molecular Biosciences. 2022 Apr. 9:871161.

Yilun Sun^#, Yang Zhang^#, Christopher W. Schultz, Yves Pommier, and Anish Thomas. CDK7 inhibition synergizes with topoisomerase I inhibition in small cell lung cancer by inducing ubiquitin-mediated proteasomal degradation of RNA polymerase II. Molecular Cancer Therapeutics. 2022 Jul 13;mct.21.0891.

Dragomir B. Krastev^#, Shudong Li^#, Yilun Sun^#, Andrew Wicks, Daniel Weekes, Luned M. Badder, Eleanor G. Knight, Rebecca Marlow, Mercedes Pardo Calvo, Yu Lu, Tanaji T. Talele, Jiri Bartek, Jyoti Choudhary, Yves Pommier, Stephen J. Pettitt, Andrew Tutt, Kristijan Ramadan, Christopher J. Lord. The ubiquitin-dependent ATPase p97 removes cytotoxic trapped PARP1 from chromatin. Nature Cell Biology. Jan;24(1):62-73.

Yicong Wu, Xiaofei Han, Yijun Su, Melissa Glidewell, Jon Daniels, Jiamin Liu, Titas Sengupta, Ivan Rey- Suarez, Robert Fischer, Akshay Patel, Christian Combs, Junhui Sun, Xufeng Wu, Ryan Christensen, Corey Smith, Lingyu Bao, Yilun Sun, Yves Pommier, Yun-Bo Shi, Elizabeth Murphy, Qionghai Dai, Clare Waterman, Sougata Roy, Arpita Upadhyaya, Daniel Colón-Ramos, Patrick La Riviere, Hari Shroff. Multiview super-resolution microscopy. Nature. 2021 Dec;600(7888):279-284.

Yilun Sun*, Jiji Chen, Shar-yin N. Huang, Yijun P. Su, Wenjie Wang, Keli Agama, Sourav Saha, Lisa Miller Jenkins, John M. Pascal, Yves Pommier*. PARylation controls the repair of topoisomerase I DNA- protein crosslinks by preventing their proteasomal degradation and inducing their deubiquitylation. Nature Communications. 2021 Aug 18;12(1):5010. 

Anish Thomas, Nobuyuki Takahashi, Vinodh Rajapakse, Xiaohu Zhang, Yilun Sun, Michele Ceribelli, Kelli Wilson, Yang Zhang, Erin Beck, Linda Sciuto, Samantha Nichols, Brian Elenbaas, Janusz Puc, Heike Dahmen, Astrid Zimmermann, Jillian Varonin, Christopher Schultz, Sehyun Kim, Carleen Klumpp-Thomas, Lu Chen, Jameson Travers, Crystal McKnight, Sam Michael, Zina Itkin, Sunmin Lee, Akira Yuno, Min- Jung Lee, Chris Redon, Jessica Kindrick, Cody Peer, Jun Wei, Mirit Aladjem, William Figg, Seth Steinberg, Jane Trepel, Frank Zenke, Yves Pommier, Javed Khan, Craig Thomas. Therapeutic targeting of ATR yields durable regressions in high replication stress tumors. Cancer Cell. 2021 Apr 12;39(4):566-579.e7.

Yilun Sun*, Lisa MM Jenkins, Yijun Su, Karin C. Nitiss, John L. Nitiss*, Yves Pommier*. A conserved SUMO pathway repairs topoisomerase DNA-protein cross-links by engaging ubiquitin-mediated proteasomal degradation. Science Advances. 2020 Nov 13;6(46):eaba6290. 

Yilun Sun, Liton Kumar Saha, Sourav Saha, Ukhyun Jo, Yves Pommier. Debulking of topoisomerase DNA-protein crosslinks (TOP-DPC) by the proteasome, non-proteasomal and non-proteolytic pathways. DNA Repair (Amst). 2020 Oct;94:102926.

Yilun Sun^#, Sourav Saha^#, Wenjie Wang, Liton Kumar Saha, Shar-Yin Naomi Huang, Yves Excision repair of topoisomerase DNA-protein crosslinks (TOP-DPC). DNA Repair (Amst). 2020 Mar 7;89:102837.

Yves Pommier, Yilun Sun, Shar-yin Huang and John L. Nitiss. Roles of eukaryotic topoisomerases in transcription, replication and genomic stability. Nature Reviews Molecular Cell Biology. 2016 Nov;17(11):703-721.