Work Left to Do: Q&A with Mitchell A. Lazar, MD, PhD

Despite being inducted into what he calls the “Endocrine Hall of Fame” upon receiving this year’s Fred Conrad Koch Lifetime Achievement Award, Mitchell A. Lazar, MD, PhD, reflects on his achievements and his legacy. However, he wants to make sure that despite such lofty recognition, he assures us that he still has “a couple of achievements” left in his lifetime!

With culture wars and pandemic fears at their peak in 2020, Mitchell A. Lazar, MD, PhD, wanted the world to know his laboratory was a place of tolerance and acceptance. Adding an inclusive message on his lab website may seem like a simple gesture to many, but for Lazar and his team, it ranked high among his great deeds. Just one of many that helped earn him the Endocrine Society’s highest honor — The 2023 Fred Conrad Koch Lifetime Achievement Laureate Award.

Lazar is the Willard and Rhoda Ware Professor in Diabetes and Metabolic Diseases at the Perelman School of Medicine at the University of Pennsylvania, where he joined the faculty in 1989. He is also the founding director of the university’s Institute for Diabetes, Obesity, and Metabolism. Known for his groundbreaking work related to the basic mechanisms of nuclear receptor action and their role in obesity and diabetes, Lazar also most notably discovered the hormone resistin.

Endocrine News spoke with Lazar recently to learn more about his life reflections and what has mattered most so far.

Fred Conrad Koch was a renowned endocrinologist and the Endocrine Society’s 19th president. What does it mean to be included among past Society Lifetime Achievement honorees?

The Endocrine Society and the endocrine science it fosters represent the oldest and most successful applications of the scientific method to biomedical questions. The great accomplishments of Dr. Koch epitomize the honor of this award. I’ve been going to the Endocrine Society meetings for about 40 years. Every year someone has gotten that award, and it’s always someone that I admire. I’m a baseball fan, and in my acceptance remarks for the Koch award I said that it was like being inducted into the Endocrine Hall of Fame. Many people have been instrumental in my success, so I did my best to make sure that everyone knew how important they were to me, even if I couldn’t mention them by name.

Being honored with a Lifetime Achievement award makes people reflect on their proudest career moments. What stands out most in your career?

That is a fantastic question. I think there are so many but I’m going to compartmentalize it into the science. We made discoveries of new hormones and understanding how hormones work in a way that has relevance to endocrine diseases, including diabetes and obesity. So, for me in that context, it was the discovery of the hormone resistin, discovery of nuclear receptor PPAR-gamma, which is important for insulin resistance in diabetes, and the discovery of the nuclear receptor REV-ERB and its role as a link between circadian rhythms and metabolism.

In the course of my research, one of the things that I studied was how neurotransmitters feed back and inhibit their own production. In my clinical training I realized that’s what endocrinology was all about. It was about feedback and the concept called homeostasis, which is keeping the internal milieu constant.

But I’m equally proud of leading the University of Pennsylvania Division of Endocrinology, Diabetes, and Metabolism on a path to new heights, and that it’s continuing to thrive even after I stepped down from that position a couple of years ago. I also was founding director of a new Institute for Diabetes, Obesity, and Metabolism that I still am excited to run and see how well it’s doing, as well as the faculty I recruited to both to the IDOM and the EDM division, who are doing amazing things. Also, a huge importance are the many former trainees in my lab who are now leading in their own independent positions. These are my legacies. Finally, even though I’m thrilled to be the Endocrine Society’s Lifetime Achievement Award winner, I still think I have a couple of achievements left in my lifetime.

Can you recall the moment when you knew endocrinology would be your specialty?

I think the lesson I learned is to do science that you’re excited about. In my own case, I was a chemistry major in college and thought I would be a chemist. But because of a history of mental illness in my family, which I was sure was due to a chemical imbalance in the brain, I decided to go to medical school and get training in the biochemical basis of behavior. I did that at Stanford and was well-trained as a scientist. I really liked my project, but I also got the feeling that in my productive years as a biomedical scientist, we weren’t going to solve this problem. It was too complicated. This was 40 years ago.

But in the course of my research, one of the things that I studied was how neurotransmitters feed back and inhibit their own production. In my clinical training I realized that’s what endocrinology was all about. It was about feedback and the concept called homeostasis, which is keeping the internal milieu constant. I like to think it was a lightbulb moment but probably it was over some time that I realized this was the ideal field for me because I really enjoyed mechanistic thinking and thought I could make a difference in advancing knowledge of how hormone action is regulated and how hormones regulate metabolism.

It was over some time that I realized this was the ideal field for me because I really enjoyed mechanistic thinking and thought I could make a difference in advancing knowledge of how hormone action is regulated and how hormones regulate metabolism.

What is your lab team currently working on at the University of Pennsylvania?

In one sentence, I would say we’re working on understanding the mechanisms by which hormones, through nuclear receptors, regulate gene expression in a way that affects metabolism and circadian rhythms.

The Lazar Lab website (med.upenn.edu/lazarlab) has a banner that includes the message: “We believe science is real, love is love, Black lives matter, Immigrants are welcome, Stop Asian Hate…” A version of this has been popular on yard signs but I’ve never seen it on a lab website. What motivated you to include the message on yours?

Well, I’m not ashamed to tell you that it was during the pandemic and some of the societal unrest of the last few years that I really wanted to make a statement and my lab members wanted to make a statement. My lab members are younger than me. They’re quite a diverse group, and we thought it was important to say something.

Actually, the original version of that had everything but the stop Asian hate, and yet so many scientists in my lab and elsewhere are either Asian-Americans or from Asia. During the COVID-19 crisis, my Chinese trainees were really singled out in society by…it was related to some of the political things that were going on, and people were blaming them in the street for COVID-19. So, we added that. Again, not unique in any way. We didn’t invent that. I just felt it was really important to make that statement. Now that some of the acute issues may be over, the whole issue is not over. It reminds us, and hopefully other people perusing our website, that we still have work to do.

—Shaw is a freelance journalist based in Carmel, Ind. She is a regular contributor to Endocrine News and writes the monthly Laboratory Notes column.