Margaret A. Goodell

From the 2026 National Summit on Hematologic Cancers

Eukaryotic cells adjust biochemical pathways in response to environmental stressors, stalling energetically costly processes such as protein synthesis and ribosome biogenesis. Ribosome biogenesis occurs within the multiphase nucleolus that contains three layers roughly corresponding to ribosomal RNA (rRNA) transcription, processing, and assembly. While nucleolar perturbations induced by drug treatments and optogenetic nucleolar gelation alter nucleolar stability and hinder ribosome biogenesis, it remains unclear whether nucleolar properties are actively tuned in response to metabolic and growth cues. Here, we show that nucleolar phase separation is adjusted to physiological needs. Live-cell imaging of endogenously tagged NPM1 reveals a tight relationship between NPM1 partitioning and nutrient availability. In nutrient-deprived conditions, NPM1 levels in the nucleolus increase, indicative of stabilized phase separation and a more gel-like state. Indeed, we show that rRNA diffusion decreases and the nucleolar meshwork contracts. Furthermore, this change corresponds to decreased rRNA processing, suggesting that reduced transport properties prevent the release of immature ribosome subunits from the nucleolus. Mechanistically, we show that these changes are driven by ATP levels, which broadly affect the energetically expensive process of ribosome biogenesis. Upon restoration of ATP levels by nutrient reintroduction, nucleolar composition returns to normal within minutes, suggesting active regulation. Taken together, our findings reveal that the biophysical properties of the nucleolus are not fixed, but are actively remodeled by cellular energy levels, linking phase separation dynamics to metabolic control of ribosome biogenesis.

Margaret (Peggy) Goodell has significantly advanced our understanding of haematopoietic stem cells – the stem cells that develop into different types of specialised blood cells. She is Professor and Chair of the Department of Molecular and Cellular Biology at Baylor College of Medicine in Houston, TX, USA. Peggy completed her PhD at the University of Cambridge, UK, before returning to the USA to carry out postdoctoral work at the Whitehead Institute for Biomedical Research, in Cambridge, MA, where she pioneered a novel technique for isolating haematopoietic stem cells, known as the ‘side population’ method. She then joined Baylor College of Medicine in 1997 to start her own lab and has stayed there since. Peggy's research focuses on regulatory mechanisms in haematopoietic stem cells and how these go awry during ageing and disease. The significance of her research has been recognised by multiple prestigious awards, including the Tobias Award from the International Society for Stem Cell Research and the Dameshek Prize from the American Society of Hematology. In this ‘A Model for Life’ interview, we discuss Peggy's impressive career path, the parallels between ageing and cancer in the blood, and the lessons we can learn from stem cell biology to understand and mitigate disease.