Sihan Wu - Children's Medical Center Research Institute (CRI)

Sihan Wu Lab

Research Focus

Chromosomes carry the genetic blueprint of human life that tells our cells how to function. One of the most common genetic alterations in cancer is oncogene amplification. Oncogenes are genes known to promote cancer formation and growth. Instead of two copies, a cancer cell might have 10, 20, 30, or even more copies of an oncogene, which promotes unrestrained proliferation. However, many amplified oncogenes are not physically located where the genomic maps indicate. Instead, they frequently jump off the chromosome and amplify as circular extrachromosomal DNA (ecDNA) particles, especially in the most aggressive cancer types, including brain, lung, and breast cancers. Accumulating evidence suggests that ecDNA drive malignant behaviors in cancer cells, such as drug resistance, but our understanding of ecDNA is limited.

The long-term goal of our lab is to understand the functions of ecDNA and how ecDNA is maintained in cancer. We are integrating several approaches (sequencing, cytogenetic profiling with high-resolution imaging, and bioinformatics) to tackle these questions. If we can understand these mechanisms, we can develop specific therapeutic strategies to eliminate ecDNA and target oncogenes that are currently undruggable.

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…

Research Projects

Molecular functions of ecDNA in cancer

Molecular co-dependency of ecDNA in cancer

Molecular functions of ecDNA in cancer

Molecular co-dependency of ecDNA in cancer

Lab News

May 1, 2024

Small cell lung cancer acquires cross-resistance due to extrachromosomal DNA amplification of MYC paralogs

Summary: Small cell lung cancer (SCLC) presents as a highly chemosensitive malignancy but acquires cross-resistance after …

Cancer Biology

April 12, 2023

The presence of extrachromosomal DNA can accelerate cancer formation

Oncogene amplification on extrachromosomal DNA (ecDNA) drives the evolution of tumours and their resistance…

June 16, 2022

UTSW researchers part of winning global team in Cancer Grand Challenges

UT Southwestern researchers Zhijian “James” Chen, Ph.D., and Sihan Wu, Ph.D., are part of a team that…

Select Publications

Lin, M.S., Jo, S.Y., Luebeck, J., Chang, H.Y., Wu, S., Mischel, P.S., Bafna, V. (2024). Transcriptional immune suppression and up-regulation of double-stranded DNA damage and repair repertoires in ecDNA-containing tumors. Elife 12 :RP88895. (PubMed)

Pal Choudhuri, S., Girard, L., Lim, J.Y.S., Wise, J.F., Freitas, B., Yang, D., Wong, E., Hamilton, S., Chien, V.D., Kim, Y.J., Gilbreath, C., Zhong, J., Phat, S., Myers, D.T., Christensen, C.L., Mazloom-Farsibaf, H., Stanzione, M., Wong, K.K., Hung, Y.P., Farago, A.F., Meador, C.B., Dyson, N.J., Lawrence, M.S.,# Wu S.,# and B.J. Drapkin.# (2024) Acquired Cross-resistance in Small Cell Lung Cancer due to Extrachromosomal DNA Amplification of MYC paralogs. Cancer Discovery 14, 804-827. (PubMed)

Luebeck, J., Ng, A.W.T., Galipeau, P.C., Li, X., Sanchez, C.A., Katz-Summercorn, A., Kim, H., Jammula, S., He, Y., Lippman, S.M., Verhaak, R.G.W., Maley, C.C., Alexandrov, L.B., Reid, B.J., Fitzgerald, R.C., # Paulson, T.G.,# Chang, H.Y.,# Wu, S.,# Bafna, V.,# and P.S. Mischel.# (2023). Extrachromosomal DNA in the cancerous transformation of Barrett’s esophagus. Nature 616, 798-805. (PubMed)

Chen, P.B., Fiaux, P.C., Zhang, K., Li, B., Kubo, N., Jiang, S., Hu, R., Rooholfada, E., Wu, S., Wang, M., Wang, W., McVicker, G., Mischel, P.S., and B. Ren. (2022). Systematic discovery and functional dissection of enhancers needed for cancer cell fitness and proliferation. Cell Reports 41, 111630. (PubMed)

Lange, J.T., Rose, J.C., Chen, C.Y., Pichugin, Y., Xie, L., Tang, J., Hung, K.L., Yost, K.E., Shi, Q., Erb, M.L., Rajkumar, U., Wu, S., Taschner-Mandl, S., Bernkopf, M., Swanton, C., Liu, Z., Huang, W., Chang, H.Y., Bafna, V., Henssen, A.G., Werner, B., and P.S. Mischel. (2022). The evolutionary dynamics of extrachromosomal DNA in human cancers. Nature Genetics 54, 1527-1533. (PubMed)

Hung, K.L., Yost, K.E., Xie, L., Shi, Q., Helmsauer, K., Luebeck, J., Schöpflin, R., Lange, J.T., Chamorro González, R., Weiser, N.E., Chen, C., Valieva, M.E., Wong, I.T., Wu, S., Dehkordi, S.R., Duffy, C.V., Kraft, K., Tang, J., Belk, J.A., Rose, J.C., Corces, M.R., Granja, J.M., Li, R., Rajkumar, U., Friedlein, J., Bagchi, A., Satpathy, A.T., Tjian, R., Mundlos, S., Bafna, V., Henssen, A.G., Mischel, P.S., Liu, Z., and H.Y. Chang. (2022). ecDNA hubs drive cooperative intermolecular oncogene expression. Nature 600, 731-736. (PubMed)

Wu, S., Bafna, V., Chang, H. Y., and P.S. Mischel. (2022). Extrachromosomal DNA: An Emerging Hallmark in Human Cancer. Annual Review of Pathology: Mechanisms of Disease 17, 367-386. (PubMed)

Wu, S., Bafna, V., and P.S. Mischel. (2021). Extrachromosomal DNA (EcDNA) in Cancer Pathogenesis. Current Opinion in Genetics & Development 66, 78–82. (PubMed)

Kim, H., Nguyen, N.-P., Turner, K., Wu, S., Gujar, A. D., Luebeck, J., Liu, J., Deshpande, V., Rajkumar, U., Namburi, S., Amin, S. B., Yi, E., Menghi, F., Schulte, J. H., Henssen, A. G., Chang, H. Y., Beck, C. R., Mischel, P. S., Bafna, V., and R.G.W. Verhaak. (2020). Extrachromosomal DNA Is Associated with Oncogene Amplification and Poor Outcome across Multiple Cancers. Nature Genetics 52, 891–897. (PubMed)

Cai, J., Liu, W., Wong, C. W., Zhu, W., Lin, Y., Hu, J., Xu, W., Zhang, J., Sander, M., Wang, Z., Dan, J., Zhang, J., Liu, Y., Guo, L., Qin, Z., Liu, X., Liu, Y., Yan, G., Wu, S., and J. Liang. (2020). Zinc-Finger Antiviral Protein Acts as a Tumor Suppressor in Colorectal Cancer. Oncogene 39, 5995–6008. (PubMed)

Bi, J., Chowdhry, S., Wu, S., Zhang, W., Masui, K., and P.S. Mischel. (2020). Altered Cellular Metabolism in Gliomas — an Emerging Landscape of Actionable Co-Dependency Targets. Nature Reviews Cancer 20, 57–70. (PubMed)

Wu, S., Turner, K. M., Nguyen, N., Raviram, R., Erb, M., Santini, J., Luebeck, J., Rajkumar, U., Diao, Y., Li, B., Zhang, W., Jameson, N., Corces, M. R., Granja, J. M., Chen, X., Coruh, C., Abnousi, A., Houston, J., Ye, Z., Hu, R., Yu, M., Kim, H., Law, J. A., Verhaak, R. G. W., Hu, M., Furnari, F. B., Chang, H. Y., Ren, B., Bafna, V., and P.S. Mischel. (2019). Circular EcDNA Promotes Accessible Chromatin and High Oncogene Expression. Nature 575, 699–703. (PubMed)

#Co-corresponding author