Defining tumor-specific vulnerabilities by mapping oncogenic structural variation in osteosarcoma

What this episode covers

Andrew Clugston, PhD, a postdoctoral fellow in the Sweet-Cordero Lab at UCSF joins us on OsteoBites to discuss his OutSmarting Osteosarcoma funded work, in partnership with the RISE Foundation, on defining tumor-specific vulnerabilities by mapping oncogenic structural variation in osteosarcoma.The genomes of osteosarcoma (OS) cancer cells are among the most complex cancer genomes ever observed. Initially formed by hundreds to thousands of incorrectly repaired DNA breaks (structural variants; SVs), OS genomes contain DNA structures that are unique to that patient and tumor cell, combining genes and regulatory features from across the genome in ways that effectively re-wire that cell’s gene expression mechanisms. OS cells are also susceptible to further SVs over time and in response to treatment, potentially allowing OS tumors to evolve rapidly. But these complex and tumor-specific genomic structures may also harbor tumor-specific vulnerabilities. By mapping the many unique DNA structures among patient-derived OS tumor cells, Dr. Clugston has attempted to demonstrate that it is possible both to describe the essential structures within these cells and to search them for novel target genes vulnerable to existing drugs and treatment protocols. Using chromatin conformation capture sequencing (HiC) to observe the shape of the genome and optical genome mapping (OGM) to identify tumor-specific DNA structures, Dr. Clugston has produced tumor-specific maps for multiple patient-derived OS tumor cell lines and has begun development of a search process based on long-read mapping techniques that he hopes will inform future patient-specific treatment protocols.Andrew Clugston grew up in the small town of Lake Luzerne, New York. He received a BS in Biochemistry and an MS in Chemistry at the Rochester Institute of Technology, and he received his PhD in Integrative Systems Biology at the University of Pittsburgh. During his PhD he learned to use and develop bioinformatics tools and techniques to study the role of the genome in kidney as well as eye development, and in the process became fascinated with the importance of 3-dimensional organization in regulating cell behavior. Andrew has since joined the Sweet-Cordero laboratory in the Pediatric Oncology Division at the University of California San Francisco as a Postdoctoral Fellow. There, he applies his knowledge and skillset to study how disruptions in these organizational principles allow osteosarcoma cells to develop and proliferate, and how these changes reveal tumor-specific vulnerabilities that can be exploited for fast and effective treatment options that improve the lives of patients.

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