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…
Full Bio

Research Projects

July 20, 2021
Dr. Sihan Wu recently became the institute’s tenth faculty member and principal investigator. He…

Select Publications

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 [Epub ahead of print] (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 authorMar

Lab Members

Wenyue Liu, Ph.D.

Postdoctoral Fellow, William Prinz Lab, UT Southwestern Medical Center
Postdoctoral Fellow (2021-2023)

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