Investigation (ASCI) has selected Peter Tontonoz to receive 2022’s Stanley J. Korsmeyer Award, recognizing his foundational discoveries in lipid metabolism and his dedication to excellence in mentorship (Figure 1). Dr. Tontonoz is the Frances and Albert Piansky Endowed Chair and Distinguished Professor of Pathology and Laboratory Medicine and of Biological Chemistry at the University of California Los Angeles (UCLA), Co-Director of the UCSD/UCLA Diabetes Research Center, and Vice Chair for Research in UCLA’s Department of Pathology and Laboratory Medicine. His research has revealed that the lipid-activated nuclear receptors LXR (liver X receptor) and PPAR (peroxisome proliferator–activated receptor) coordinate lipid metabolism and modulate immunity and inflammation, demonstrating important roles for LXR and PPAR signaling pathways in atherosclerosis, insulin resistance, and immune tolerance. Recently, Dr. Tontonoz spoke with the JCI about his extraordinary scientific career. JCI: What first sparked your interest in science, and how did you eventually decide to pursue an MD/PhD? Tontonoz: I remember taking a high school science course where I had to design experiments to show that paramecia would chemotax. I enjoyed that sort of practical experimentation, and that was my first insight into what actually doing science is like. When I got to college, I worked on yeast protein kinases for an assistant professor who had just been hired at Wesleyan. From that first moment setting foot in a molecular biology laboratory, I knew that that’s what I wanted to do. I just thought being in the lab was the greatest thing, and I was there all the time. I stayed at school over the summers so I could continue to work in the lab, and basically, I haven’t left the lab since. Even when I went to medical school, I was still always in the lab. I found the subject matter intellectually interesting, but practically, I really liked being in the laboratory and doing experiments. I’d never heard of such a thing as an MD/PhD when I went to college. I found out about that only during college, learning more about what the options were. It seemed like a good option for someone like me who really was very interested in science and academically interested in medicine. But I always knew I would do science as some component of my life from the moment I stepped in a lab. JCI: Your PhD mentor, Bruce Spiegelman, has described your PhD research as a turning point for his lab (1). Would you tell us the story of those findings? Tontonoz: The work was interesting to me because it really was a big open question. Back then, it was the stage in which people were identifying tissue-specific transcription factors and showing that those transcription factors did important things in different tissues. A few years earlier, MyoD, the transcription factor that makes muscle, had been discovered and characterized (2). I remember reading that paper thinking,“Wow, I would love to discover this for fat,” and Bruce was thinking the same thing.

So we set out to try to identify the master transcription factor for fat using a twopronged approach: we picked a fat cell–specific gene, aP2, and tried to figure out the transcription factors regulating that gene, a very laborious process. We cut up fragments of the gene one by one and ran reporter assays with the fragments of DNA hooked up to a reporter. We found this little region in the promoter that, if hooked up to any gene, would confer fat-specific expression in cultured cells. We then took a more molecular biology–based approach: the sequence looked like a nuclear hormone receptor binding site, so we went looking for members of the nuclear hormone receptor family …