Sihan Wu, Ph.D., assistant professor a promising young scientist with an extensive background in cancer genetics and genomics, was recruited to the Children's Research Institute at The University of Texas Southwestern Medical Center in 2021 with the support of a CPRIT Recruitment of First-Time, Tenure-Track Faculty Members award. Dr. Wu obtained his Ph.D. from the Zhongshan School of Medicine at Sun Yat-sen University, where he majored in biotechnology. His doctoral research focused on how genetic alterations contribute to brain tumor development and led to the discovery that dysregulation of non-coding microRNAs contributes to the development of glioblastoma. After receiving his Ph.D., he started as a postdoctoral fellow at the Ludwig Institute for Cancer Research at the University of California in the lab of Dr. Paul Mischel. There, Dr. Wu studied the structure and function of ecDNA in cancer, uncovering its circular shape and the functional impact of its unique physical conformation.
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Sihan Wu, Ph.D., assistant professor a promising young scientist with an extensive background in cancer genetics and genomics, was recruited to the Children's Research Institute at The University of Texas Southwestern Medical Center in 2021 with the support of a CPRIT Recruitment of First-Time, Tenure-Track Faculty Members award. Dr. Wu obtained his Ph.D. from the Zhongshan School of Medicine at Sun Yat-sen University, where he majored in biotechnology. His doctoral research focused on how genetic alterations contribute to brain tumor development and led to the discovery that dysregulation of non-coding microRNAs contributes to the development of glioblastoma. After receiving his Ph.D., he started as a postdoctoral fellow at the Ludwig Institute for Cancer Research at the University of California in the lab of Dr. Paul Mischel. There, Dr. Wu studied the structure and function of ecDNA in cancer, uncovering its circular shape and the functional impact of its unique physical conformation.
One of the most common genetic alterations causing cancer is oncogene amplification. Recent studies into the ecDNA landscape of clinical tumor samples have revealed a surprisingly high prevalence of ecDNA in some human cancers, especially in aggressive cancers like those of the brain, lung, and breast. Accumulating evidence suggests that ecDNA is driving malignant behaviors in cancer cells, such as drug resistance, but our understanding of ecDNA is limited. Dr. Wu, a promising young scientist with an extensive background in cancer genetics and genomics, hopes to change this. With the generous support from a CPRIT, he conducts high-risk, high-reward research focused on understanding the maintenance mechanisms of ecDNA in cancer, such as ecDNA replication and repair, and its interaction with the innate immunity.
By integrating whole-genome sequencing, long-range optical mapping, and super-resolution imaging, Dr. Wu's research has demonstrated that ecDNA is circular. By using pan-cancer genomic and transcriptomic analyses, he also revealed that oncogenes encoded on ecDNA are among the most highly expressed genes in the transcriptome, linking elevated DNA copy with high transcription levels. He found that while ecDNA is organized into a 3D structure similar to a chromosome, it lacked higher-order compaction (i.e., heterochromatin), and displays significantly enhanced chromatin accessibility. Additionally, Dr. Wu's research has shown that ecDNA significantly enhanced ultra-long-range active chromatin contacts, providing new insight into how circular ecDNA structure impacts oncogene function, thereby bridging ecDNA biology with modern cancer genetics and epigenetics. Together, this information could allow researchers to therapeutically target the ability of ecDNAs to replicate, slowing down the expression of amplified oncogenes, including those that can't be targeted through traditional pharmacological approaches.
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