Yilun Sun, PhD

Capital Medical University, BSc, Pharmaceutical Sciences

Georgetown University, MSc, Biotechnology

University of Illinois at Chicago, PhD, Molecular Pharmacology

National Cancer Institute, NIH, Postdoctoral Fellow

National Cancer Institute, NIH, Research Fellow

Dr. Yilun Sun received his Ph.D. in Molecular Pharmacology from the University of Illinois College of Pharmacy in 2017. He joined the National Cancer Institute, NIH, in 2018 as a Postdoctoral Fellow and was promoted to Research Fellow in 2021, where he studied topoisomerases, poly(ADP-ribose) polymerases, DNA repair, and their relevance to cancer therapy.

Dr. Sun’s laboratory investigates the molecular mechanisms that repair DNA damage induced by topoisomerase inhibitors and PARP inhibitors, with a particular focus on preclinical models of lung, colorectal, and other cancers. These agents—including topotecan, irinotecan, etoposide, doxorubicin, olaparib, rucaparib, and talazoparib—are widely used in cancer chemotherapy and are increasingly being incorporated into tumor-targeted delivery platforms such as antibody-drug conjugates and nanoparticles.

A major focus of Dr. Sun’s research is the repair of topoisomerase DNA-protein crosslinks and PARP-DNA complexes, which are central cytotoxic lesions induced by topoisomerase and PARP inhibitors, respectively. His laboratory has developed immuno-biochemical assays and single-molecule fluorescence approaches to interrogate how cancer cells repair these lesions. His work has defined several repair pathways regulated by post-translational modifications, including ubiquitylation, SUMOylation, neddylation, and ADP-ribosylation. The lab also investigates proteases and nucleases that resolve non-specific DNA-protein crosslinks, including those induced by reactive aldehydes.

The long-term goal of Dr. Sun’s research is to identify and target novel DNA repair mechanisms that can improve tumor responses to topoisomerase inhibitors and PARP inhibitors. In parallel, his laboratory studies chemo-immunotherapy strategies in preclinical cancer models and uses genome-wide CRISPR screening to identify genes and pathways that compensate for the loss of topoisomerases in human cells. Dr. Sun’s laboratory is also pursuing the discovery of first-in-class inhibitors of other human topoisomerases. Through integrated in vitro cytotoxicity and in silico screening, his team is identifying and characterizing small-molecule candidates that target topoisomerases and define new opportunities for therapeutic intervention.

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

Topoisomerases, PARP, chemotherapy, 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. 

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 level. 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, John L. Nitiss*. Requirements for MRE11 endonuclease processing of topoisomerase II-mediated DNA damage in mammalian cells. 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, John L. Nitiss. Roles of eukaryotic topoisomerases in transcription, replication and genomic stability. Nature Reviews Molecular Cell Biology. 2016 Nov;17(11):703-721.

Liton Kumar Saha, Yilun Sun, Sourav Saha, Xi Yang, Yves Pommier. PARP1-driven Repair of Topoisomerase IIIα DNA-Protein Crosslinks (TOP3A-DPCs) by Cell Reports. 2024 Jul 18;43(8):114522.

Sourav Saha, Shar-Yin Naomi Huang, Xi Yang, Liton Kumar Saha, Yilun Sun, Shuaikun Su, Lisa Jenkins, Weidong Wang, Yves Pommier. The TDRD3-USP9X complex and MIB1 regulate TOP3B homeostasis and prevent deleterious TOP3B cleavage complexes. Nature Communications. 2023 Nov 18;14(1):7524.

Liton Kumar Saha, Sourav Saha, Xi Yan, Shar-yin Naomi Huang, Yilun Sun, Ukhyun Jo and Yves Pommier. Replication-associated formation and repair of human topoisomerase IIIa cleavage. Nature Communications. 2023 Apr 6;14(1):1925.

Sourav Saha, Xi Yang, Shar-Yin Naomi Huang, Keli Agama, Simone Andrea Baechler, Yilun Sun, Hongliang Zhang, Liton Kumar Saha, Shuaikun Su, Lisa Jenkins, Weidong Wang, Yves Pommier. Resolution of R-loops by topoisomerase III-β (TOP3B) in coordination with the DEAD-box helicase DDX5. Cell Reports. 2022 Jul 12;40(2):111067. 

Ukhyun Jo, Yasuhisa Murai, Keli Agama, Yilun Sun, Liton Kumar Saha, Xi Yang, Sophia Gayle, Vishwas Paralkar, Ranjini Sundaram, Jinny van Doorn, Juan C. Vasquez, Ranjit Bindra, Woo Suk Choi, and Yves Pommier. TOP1-DNA trapping by exatecan and combination therapy with ATR inhibitor. Molecular Cancer Therapeutics. 2022 Jul 5;21(7):1090-1102.

John Nitiss, Kostantin Kiianitsa, Yilun Sun, Karin C. Nitiss, and Nancy Maizels. Topoisomerase Assays. Current Protocols in Pharmacology. 2021 Oct;1(10):e250.

Franciele Faccio Busatto, Sofiane Yacine Mersaoui, Yilun Sun, Yves Pommier, Jean-Yves Masson, Jenifer Saffi. Functions of the CSB protein at Topoisomerase 2 inhibitors-induced DNA lesions. Frontier in Cell and Developmental Biology. 2021 Oct 22:9:727836.

Liliya Tyutyunyk-Massey, Yilun Sun, Nga Dao, Hannah Ngo, Mallika Dammalapati, Ashish Vaidyanathan, Manjulata Singh, Syed Haqqani, Joshua Haueis, Ryan Finnegan, Deng Xiaoyan, Steve Kirberger, Paula Bos, William Pomerantz, Yves Pommier, David Gewirtz, and Joseph Landry. Autophagy Dependent Sensitization of Triple Negative Breast Cancer Models to Topoisomerase II Poisons by Inhibition of The Nucleosome Remodeling Factor. Molecular Cancer Research. 2021 Aug;19(8):1338-1349.

Xiaofei Han, Yijun Su, Hamilton White, Kate O’Neill, Nicole Y. Morgan, Ryan Christensen, Deepika Potarazu, Harshad D. Vishwasrao, Stephen Xu, Yilun Sun, Shar-yin Huang, Mark W. Moyle, Qionghai Dai, Yves Pommier, Edward Giniger, Dirk R. Albrecht, Roland Probst, Hari Shroff. A polymer gel index-matched to water enables diverse applications in fluorescence microscopy. Lab on a Chip. 2021 Apr 20;21(8):1549-1562.

Sourav Saha, Yilun Sun, Shar-Yin Huang, Ukhyun Jo, Hongliang Zhang, Yuk-Ching Tse-Dinh, Y Pommier. DNA and RNA Cleavage Complexes and Repair Pathway for TOP3B RNA- and DNA-Protein Crosslinks. Cell Reports. 2020 Dec 29;33(13):108569.

Nicole Stantial, Anna Rogojina, Matthew Gilbertson, Yilun Sun, Hannah Miles, Samantha Shaltz, James Berger, Karin C Nitiss, Sue Jinks-Robertson, John L. Nitiss. Trapped topoisomerase II initiates formation of de novo duplications via the nonhomologous end-joining pathway in yeast. Proceedings of the National Academy of Sciences of the United States of America. 2020 Oct 27;117(43):26876-26884.

Laetitia Marzi, Yilun Sun, Shar-Yin Huang, Amy James, Simone Difilippantonio, and Yves Pommier. The indenoisoquinoline LMP517: a novel antitumor agent targeting both TOP1 and TOP2. Molecular Cancer Therapeutics. 2020 Aug;19(8):1589-1597.

Nicholas Sciascia, Wei Wu, Dali Zong, Yilun Sun, Nancy Wong, Sam John, Darawalee Wangsa, Thomas Ried, Samuel F Bunting, Yves Pommier, André Suppressing proteasome-mediated processing of topoisomerase II DNA-protein complexes preserves genome integrity. eLife. 2020 Feb 14;9. pii: e53447.

Jay Anand, Yilun Sun, Yang Zhao, Karin Nitiss, and John L. Nitiss. Detection of topoisomerase covalent complexes in eukaryotic cells. Methods in Molecular Biology, 2018;1703:283-299.

The Sun lab studies molecular mechanisms that repair DNA damage induced by topoisomerase inhibitors, poly(ADP-ribose) polymerase inhibitors, and crosslinking agents such as reactive aldehydes, with a particular focus on preclinical models of lung, colorectal, and breast cancers. The lab aims to target these DNA repair mechanisms to improve tumor responses to topoisomerase inhibitors and PARP inhibitors. In parallel, the Sun lab investigates topoisomerase biology using genome-wide CRISPR screening to identify and characterize genes and pathways that compensate for the loss of topoisomerases in human cells, while also pursuing first-in-class human topoisomerase 3A inhibitors through integrated in vitro cytotoxicity and biochemical assays and in silico modeling. The lab also studies chemo-immunotherapy strategies in preclinical cancer models.

Associate Editor, Cell Division, 2024 -present

Early Career Reviewer Board, Journal of Biological Chemistry, 2023- present

American Cancer Society Institutional Research Grant

NCI K99/R00 Pathway to Independence Award

NCI Federal Technology Transfer Award 

NCI Center for Cancer Research Excellence in Postdoctoral Research Transition Award 

NIH Fellows Award for Research Excellence (FARE)

NIH FARE Proteomics Scientific Interest Group Award

American Association for Cancer Research (AACR) Scholar-in-Training Award

Keystone Symposia Scholarship

National Science Foundation (NSF) Travel Award

W. E. Van Doren Scholarship, University of Illinois College of Pharmacy

4R00CA273171-02 (PI: Sun)

NIH/NCI

IRG-24-1290479-19-IRG (PI: Sun)

American Cancer Society