Kaelin and colleagues identified aspects of the molecular machinery in Von Hippel-Landau disease that regulates the activity of genes in response to varying levels of oxygen.

In 2019 Kaelin shared the Nobel Prize in Physiology or Medicine with Sir Peter J. Ratcliffe and Gregg L. Semenza "for their discoveries of how cells sense and adapt to oxygen availability."

See also: Jaakkola, P., Mole, D., Tian, Y., Wilson, M., Gielbert, J., Gaskell, S., Kriegsheim, A., Hebestreit, H., Mukherji, M., Schofield, C., Maxwell, P., Pugh, C. & Ratcliffe, P. 2001. Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Science, 292, 468–72.

Ratcliffe and colleagues made essentially the same discovery simultaneously with Kaelin and colleagues.