At 10am (BST), on Thursday 24th April, David Pellman will deliver the 2025 César Milstein Lecture. David Pellman is the Margaret M. Dyson Professor of Pediatric Oncology at the Dana-Farber Cancer Institute, Professor of Cell Biology at Harvard Medical School, a Howard Hughes Medical Institute Investigator and Associate Director for Basic Science at the Dana-Farber/Harvard Cancer Centre. His lecture – “Mechanisms driving the rapid evolution of genomes” – will be held in the LMB’s Max Perutz Lecture Theatre and streamed over Zoom. Anyone interested is warmly invited to join.
David’s research goals are to better understand the mechanisms behind cell division and chromosome segregation, both in their usual context and within cancer cells. His research group uses a variety of methods, and notably developed Look-Seq which combines long-term, live-cell imaging with single cell isolation and single cell genomics. This enables them to directly relate morphological phenotype to a cell’s genotype, meaning they can recreate and examine the dramatic mutational processes that drive rapid genome evolution in cancers.
Their work has already resulted in several significant breakthroughs, including helping to discover formin-dependent actin assembly and a mechanism for positioning mitotic spindles within asymmetrically dividing cells. David’s research has also illustrated how whole genome duplication can alter cell physiology, drive evolutionary adaption and encourage tumour development. Furthermore, he discovered a mechanism which explains chromothripsis, a complex chromosomal rearrangement where chromosomes are broken and reassembled which is found in cancers and congenital diseases.
David’s work has been recognised with several awards, including the AACR-G.H.A. Clowes Award for Outstanding Basic Cancer Research, the Stohlman Scholar Award from the Leukemia and Lymphoma Society of America and the E. Mead Johnson Award for Research in Pediatrics. He is a member of the National Academy of Medicine, the Association of American Physicians, the American Association for the Advancement of Science and the American Academy of Arts and Sciences.
Lecture abstract
Genome evolution has long been viewed as a gradual process, with small-scale genetic alterations accruing over many generations. However, it is now appreciated that saltatory mutational events, driving rapid evolution, can be layered onto gradual Darwinian evolution. These episodic events are particularly common in cancer, where they generate highly rearranged genomes. At least some of these processes cause human congenital disease, can be passed through the germline, and may contribute to organismal evolution. My group has contributed to this paradigm by identifying mechanisms and consequences of these catastrophic mutational events, linking them to common errors in cell division. My talk will focus on the mechanism of chromothripsis, a catastrophic mutational process that originates from aberrations in the architecture of the nucleus. I will focus on the processes that fragment chromosomes during chromothripsis.
Background information
The César Milstein Lecture is named in honour of César Milstein, an LMB Nobel Laureate. This named lecture is one of a series of named lectures organised by the LMB and given by eminent scientists from around the world. These talks are supported financially by AstraZeneca and the Max Perutz Fund.
César was born in Argentina in 1927. After completing PhDs in both Buenos Aires and Cambridge, he embarked on a brief spell of research in Argentina before he joined the LMB in 1963. César then spent the rest of his career and his life here.
César developed an early interest in immunology, with his research concentrated on antibody structure and diversity. In the early 1970s, he and his postdoc, Georges Köhler, developed the technique used to produce monoclonal antibodies. This work led to them being jointly awarded the 1984 Nobel Prize in Physiology or Medicine. The technique developed by César and Georges has since been developed further by LMB colleagues for therapeutic applications, leading to the creation of several MRC spin-out companies. César continued his research on how somatic mutation arises in immunoglobulin genes. He died in Cambridge on 24th March 2002.