Dr. Bill Kaelin Studies Tumor Suppressors to Improve the Understanding of Cancer Biology

Dr. Bill Kaelin is a physician scientist at Dana-Farber Cancer Institute and Harvard Medical School who investigates the mechanisms of tumor suppressor proteins. 

When he was a medical oncology clinical fellow, Dr. Kaelin studied the tumor suppressor gene RB1, which was shown to regulate cellular replication. Even though he never intended to be a lab researcher, this experience helped foster an interest in cancer genetics. According to him, “By identifying common gene mutations across different cancer types, one could let the cancer tell you which genes it cared about.”  

Upon establishing an independent lab, Dr. Kaelin focused his research on the von Hippel-Lindau (VHL) tumor suppressor protein. He discovered VHL’s role as a regulator of oxygen sensing and angiogenesis (the formation of new blood vessels and a process that enables tumor growth in cancer). Based on this work, he was awarded the Nobel Prize in Physiology or Medicine in 2019 with Sir Peter J. Ratcliffe and Gregg L. Semenza. 

Dr. Kaelin describes himself as a disease-oriented basic researcher and said, “With every great piece of translational work, you can draw a clear line backwards through time and see how it built upon basic and fundamental discoveries before a light bulb moment, where enough was known to do something useful. I think that’s the way real translation happens.” 

Over time, Dr. Kaelin has seen approaches, technologies, and model systems come in-and-out of vogue. “What doesn’t go out of style, is learning how to think clearly and logically,” stated Dr. Kaelin when asked about his approach to advising students. For example, he teaches them how to deconstruct complex biological questions and to devise experiments with positive and negative controls. With regards to the latter, he implores trainees to consider the least, rather than most, interesting interpretations of their data as a motivation for including ever more powerful controls and corroborating lines of evidence before drawing conclusions.  

Dr. Kaelin argues that training in a lab that focuses on biological questions and instilling scientific discipline is more important than choosing a lab to learn a specific technology. He explained, “There is a danger of getting too wedded to a particular technology or approach, where you become a hammer that’s always looking for nails.”