William Kaelin

William Kaelin at Dana-Farber shared the 2019 Nobel Prize in Physiology or Medicine for discovering how cells sense and adapt to oxygen levels through the VHL-HIF pathway, foundational work for understanding hypoxia-driven cancer metabolism. His subsequent contributions to IDH mutation biology and the role of 2-hydroxyglutarate (2-HG) as an oncometabolite have been seminal. He demonstrated that IDH mutant-produced 2-HG inhibits alpha-ketoglutarate-dependent enzymes to remodel the epigenome, providing the mechanistic basis for IDH inhibitor development. His comprehensive work on hypoxia, IDH mutations, and metabolic reprogramming in cancer has defined key aspects of cancer metabolic biology.