LC Seminar 12/2- Dr. Guiping Wang

Guiping Wang, PhD, Postdoctoral, Fellow, School of Medicine, Stanford University

Time: 2:00 PM

Enhancing transcription-replication conflict to target cancers driven by extrachromosomal DNA

Genetic alterations in cancer can occur not only on chromosomes but also extrachromosomally within the nucleus. Extrachromosomal DNA (ecDNA) has a large circular DNA structure (~100kb – 5Mb) that is uniquely found cancer cells. ecDNA has been identified in many human cancer types and to carry not only oncogenes but also regulatory elements. A cancer cell can contain hundreds of copies of ecDNA, which lacks centromere and segregate stochastically during mitosis. Clinically, presence of ecDNA increased after targeted and cytotoxic therapies, and was associated with metastasis and poorer patient outcomes. Despite the clinical importance, actionable vulnerabilities of ecDNA remain to be identified. In this talk, I will share our recent discovery of a key vulnerability of ecDNA-driven tumors: increased transcription replication conflicts and heightened replication stress on ecDNA. My research program will integrate and develop image- and sequencing-based quantitative genomics methods to study gene regulation across scales, from molecular interactions to cellular and tissue-scale behaviors.

Location: Laufer Center Lecture Hall 101