Sihan Wu

My lab focuses on understanding the molecular function and dependency of extrachromosomal DNA (ecDNA) in human cancer and leveraging this knowledge to develop effective therapeutic strategies to treat ecDNA-driven cancer. In cancer, oncogene-containing DNA segments frequently jump off the chromosome and form circular ecDNA particles, especially in the most aggressive cancer types, including brain, lung, and breast cancers. Given the prevalence of ecDNA in cancer, my lab seeks to interrogate the molecular function of ecDNA and the molecular mechanism that maintains the ecDNA population in the cancer genome. By integrating high-resolution imaging and modern sequencing technologies, we have begun to understand how the structure of ecDNA impacts oncogene function, including how its circular shape and hyper-accessible chromatin promote massive oncogene expression. Further, by revealing its unequal segregation behavior during mitosis, we show that ecDNA enables rapid oncogene copy number gain and facilitates genetic heterogeneity, therefore driving tumor evolution and therapeutic resistance. My lab is also interested in revealing the mechanism supporting ecDNA function, including how it replicates, transcribes, and repairs. This information may allow us to therapeutically target ecDNA, undermining the expression of amplified oncogenes, including the ones that still cannot be targeted through traditional pharmacological approaches.