Hosted by the School of Medicine at Cardiff University

David Pellman, M.D. is the Margaret M. Dyson Professor of Pediatric Oncology at the Dana-Farber Cancer Institute, a Professor of Cell Biology at Harvard Medical School, an Investigator of the Howard Hughes Medical Institute, and the Associate Director for Basic Science at the Dana-Farber/Harvard Cancer Center.

His group is working on problems at the interface between the cell biology of the nucleus and the stability of the genome. One of the processes we study is chromothripsis, massive chromosome rearrangement restricted to one or a few chromosomes. The Lab previously used a combination of live-cell imaging and single cell whole genome sequencing to show that chromothripsis occurs when chromosomes are partitioned into aberrant structures of the nucleus called micronuclei or chromosome bridges. In the first cell division cycle, the affected chromosome is shattered and, because of random distribution of fragments to daughter cells, the copy-number outcome is oscillations between two copy number levels with segments either retained or lost. However, during long term clonal expansion, the picture changes and the copy-number pattern becomes dominated by segmental gain – a pattern commonly found in diseases such as cancer. Prof. Pellman will present support for a new model for chromothripsis that they call the Breakage-Replication/Fusion cycle that explains copy number gains associated with chromothripsis. 

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