Following his post-doctorate, Kaelin set up a laboratory at Dana-Farber in 1993 to continue his research on tumor suppression. He had become interested in
Von Hippel–Lindau disease (VHL). VHL tumors, caused by gene mutation, were known to be
angiogenic, creating blood vessels that secreted
erythropoietin (EPO), a hormone known to be part of the body's mechanic to react to
hypoxia, or low oxygen levels in the blood. Kaelin hypothesized that there may be a connection between the formation of VHL tumors and the deficiency of the body to detect oxygen. Kaelin's research found that in VHL subjects, there are genes that express the formation of a protein critical in the EPO process, but which the mutation suppressed. Kaelin's work aligned with that of
Peter J. Ratcliffe and
Gregg Semenza who separately had identified a two-part protein,
hypoxia-inducible factors (HIF) that was essential to EPO production and which was triggered by oxygen levels in the blood. Kaelin's work found that the VHL protein would help regulate the HIF, and in subjects where the VHL proteins were not present, the HIF would overproduce EPO and lead to cancer. The combined work of Kaelin, Ratcliffe, and Semenza identified the pathway of how cells detect and react to oxygen levels in the blood, and have led to the development of drugs to help patients with
anaemia and
kidney failure. ==Personal life==