Sihan Wu, Ph.D.

Dr. Sihan Wu has an extensive background in cancer genetics and genomics. After graduating from Sun-Yat-sen University (SYSU), where he majored in biotechnology in the Life Science School, he obtained his Ph.D. at the Zhongshan School of Medicine at SYSU. His doctoral research focused on how genetic alterations contribute to brain tumor development. His work led to the discovery that dysregulation of non-coding microRNAs contributes to the development of glioblastoma. After receiving his Ph.D., he initiated postdoctoral research at the Ludwig Institute for Cancer Research at the University of California, San Diego, under Dr. Paul Mischel’s mentorship. There he studied the structure and function of extrachromosomal DNA (ecDNA) in cancer, uncovering its circular shape and the functional impact of its unique physical conformation.

In 2021, Dr. Wu joined Children’s Medical Center Research Institute at UT Southwestern as an Assistant Professor and became a Cancer Prevention and Research Institute of Texas (CPRIT) Scholar. He holds a secondary appointment in the Department of Pediatrics.

The Wu laboratory is working to understand the functions of ecDNA and how ecDNA is maintained in cancer. They are integrating several approaches (modern sequencing technologies, cytogenetic profiling with high-resolution imaging, and bioinformatics) to tackle these questions. Understanding these mechanisms will help them develop specific therapeutic strategies to eliminate ecDNA and target oncogenes that are currently undruggable to treat a variety of cancers.

Graduate School

Sun Yat-Sen University (2014), Pharmacology

• Cancer epigenetics
• Cancer genomics
• Extrachromosomal DNA in human cancer

Featured Publications

Acquired Cross-resistance in Small Cell Lung Cancer due to Extrachromosomal DNA Amplification of MYC paralogs.

Pal Choudhuri S, Girard L, Lim JYS, Wise JF, Freitas B, Yang D, Wong E, Hamilton S, Chien VD, Kim YJ, Gilbreath C, Zhong J, Phat S, Myers DT, Christensen CL, Mazloom-Farsibaf H, Stanzione M, Wong KK, Hung YP, Farago AF, Meador CB, Dyson NJ, Lawrence MS, Wu S, Drapkin BJ, Cancer Discov 2024 Feb

Extrachromosomal DNA in the cancerous transformation of Barrett's oesophagus.

Luebeck J, Ng AWT, Galipeau PC, Li X, Sanchez CA, Katz-Summercorn AC, Kim H, Jammula S, He Y, Lippman SM, Verhaak RGW, Maley CC, Alexandrov LB, Reid BJ, Fitzgerald RC, Paulson TG, Chang HY, Wu S, Bafna V, Mischel PS, Nature 2023 Apr 616 7958 798-805

Extrachromosomal DNA: An Emerging Hallmark in Human Cancer.

Wu S, Bafna V, Chang HY, Mischel PS, Annu Rev Pathol 2021 Nov

Extrachromosomal DNA is associated with oncogene amplification and poor outcome across multiple cancers.

Kim H, Nguyen NP, Turner K, Wu S, Gujar AD, Luebeck J, Liu J, Deshpande V, Rajkumar U, Namburi S, Amin SB, Yi E, Menghi F, Schulte JH, Henssen AG, Chang HY, Beck CR, Mischel PS, Bafna V, Verhaak RGW, Nat Genet 2020 09 52 9 891-897

Circular ecDNA promotes accessible chromatin and high oncogene expression.

Wu S, Turner KM, Nguyen N, Raviram R, Erb M, Santini J, Luebeck J, Rajkumar U, Diao Y, Li B, Zhang W, Jameson N, Corces MR, Granja JM, Chen X, Coruh C, Abnousi A, Houston J, Ye Z, Hu R, Yu M, Kim H, Law JA, Verhaak RGW, Hu M, Furnari FB, Chang HY, Ren B, Bafna V, Mischel PS, Nature 2019 Nov 575 7784 699-703

Transcriptional immune suppression and up-regulation of double-stranded DNA damage and repair repertoires in ecDNA-containing tumors.

Lin MS, Jo SY, Luebeck J, Chang HY, Wu S, Mischel PS, Bafna V, Elife 2024 Jun 12

Systematic discovery and functional dissection of enhancers needed for cancer cell fitness and proliferation.

Chen PB, Fiaux PC, Zhang K, Li B, Kubo N, Jiang S, Hu R, Rooholfada E, Wu S, Wang M, Wang W, McVicker G, Mischel PS, Ren B, Cell Rep 2022 Nov 41 6 111630

The evolutionary dynamics of extrachromosomal DNA in human cancers.

Lange JT, Rose JC, Chen CY, Pichugin Y, Xie L, Tang J, Hung KL, Yost KE, Shi Q, Erb ML, Rajkumar U, Wu S, Taschner-Mandl S, Bernkopf M, Swanton C, Liu Z, Huang W, Chang HY, Bafna V, Henssen AG, Werner B, Mischel PS, Nat Genet 2022 Sep

Targeting glioblastoma signaling and metabolism with a re-purposed brain-penetrant drug.

Bi J, Khan A, Tang J, Armando AM, Wu S, Zhang W, Gimple RC, Reed A, Jing H, Koga T, Wong IT, Gu Y, Miki S, Yang H, Prager B, Curtis EJ, Wainwright DA, Furnari FB, Rich JN, Cloughesy TF, Kornblum HI, Quehenberger O, Rzhetsky A, Cravatt BF, Mischel PS, Cell Rep 2021 Nov 37 5 109957

ecDNA hubs drive cooperative intermolecular oncogene expression.

Hung KL, Yost KE, Xie L, Shi Q, Helmsauer K, Luebeck J, Schöpflin R, Lange JT, Chamorro González R, Weiser NE, Chen C, Valieva ME, Wong IT, Wu S, Dehkordi SR, Duffy CV, Kraft K, Tang J, Belk JA, Rose JC, Corces MR, Granja JM, Li R, Rajkumar U, Friedlein J, Bagchi A, Satpathy AT, Tjian R, Mundlos S, Bafna V, Henssen AG, Mischel PS, Liu Z, Chang HY, Nature 2021 Nov

 Featured Books

Evolvement of MicroRNAs as Therapeutic Targets for Malignant Gliomas. In Evolution of the Molecular Biology of Brain Tumors and the Therapeutic Implications

Sihan Wu, Wenbo Zhu, Guangmei Yan (2013). UK, INTECH Open Access Publisher

• Gilead Research Scholar, Gilead Sciences
  (2023)
• CPRIT Scholar
  (2021)
• Forbeck Scholar, William Guy Forbeck Research Foundation
  (2021)
• Award of Excellence, poster session, UC San Diego Moore Cancer Center
  (2019)
• Ludwig Institute Kerr Award
  (2019)
• National Award for Academic Star of Doctoral Candidate, Ministry of Education of China
  (2012)
• National Scholarship for Graduated Student, Ministry of Education of China
  (2012)