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June 28, 2021
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Valuing mentorship: A conversation with Bruce M. Spiegelman, PhD

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Bruce M. Spiegelman, PhD, has been part of several scientific discoveries during his career, but he considers his accomplishments in mentorship to be just as important.

Spiegelman, the Stanley J. Korsmeyer Professor of Cell Biology and Medicine at Harvard Medical School, said the mentors he had while pursuing his doctoral degree had a lasting impact on him. He has since tried to be a strong mentor himself with the many students and colleagues he has worked with in his nearly 40 years at Harvard.

Spiegelman is the Stanley J. Korsmeyer Professor of Cell Biology and Medicine at Harvard Medical School.

“I received good mentorship, and I really do attempt to provide good mentorship for my people,” Spiegelman told Healio. “People who trained with me, I’m proud of them and what they’ve done. But it’s something I’ve always taken very seriously.”

Spiegelman’s mentorship efforts were recognized when he was named the recipient of the 2021 Albert Renold Award at the American Diabetes Association Scientific Sessions. The award is given to people who have distinguished themselves in the training and mentorship of diabetes research scientists and in the development of communities of scientists to enhance diabetes research.

Spiegelman spoke with Healio about some of his proudest accomplishments, why he believes mentorship is so important, and the future of research in cardiometabolic diseases.

Healio: What was the defining moment that led you to your field?

Spiegelman: In my postdoctoral work, I worked in Howard Green’s lab, and he developed the first culture system for adipose cells. I was interested in a basic cell biology problem of how cells differentiate. It was working with fat cells that I began to understand their role in the whole metabolic system, the role of insulin and glucose uptake. It was kind of step by step because I initially was not specifically interested in the metabolic aspect. I developed it over the years working on fat cell differentiation.

Healio: What is the best career advice you have received?

Spiegelman: The best career advice is to find a problem that interests you, focus on it, pay attention to what other people are doing, but watch with only one eye. Find your own niche, which is not a niche identical to other people’s, if possible.

Building out adipose differentiation, the physiology of adipose tissue, the molecular aspects of it, wasn’t a very popular area when I began working on it, but I liked it. I liked the fact that not everybody was doing the same experiments that I was doing. I got more enjoyment and more inspiration out of that. We had to do a lot of basic work that otherwise wouldn’t have been done if it was a well-trodden path. But it was also more fun doing stuff that wasn’t a well-trodden path.

Healio: Have you ever been fortunate enough to witness or to have been part of medical history in the making?

Spiegelman: My PhD mentor, Mark Kirschner, and another student, Don Cleveland, discovered the protein tau, which plays an important role in Alzheimer’s. It wasn’t my work, it was the group I was in, though.

We ourselves have made some good discoveries with the role of PPAR-gamma in fat differentiation. PPAR-gamma is kind of the master regulator in fat formation. My lab did that in 1994. We discovered PGC-1 alpha, which is probably the most important regulator of mitochondrial biogenesis, in 1998. You can debate whether those are huge historic moments, but they were significant. So I’ve been lucky enough to have been involved in some pretty good things.

Healio: Are you currently working on any interesting research, and if so, what is it?

Spiegelman: In terms of our metabolic work, we are very interested in what is called adaptive thermogenesis, how the body adapts to different temperatures and different diets by changing metabolic rates. It has a lot to do with obesity and type 2 diabetes. We would like to discover the basic pathways that control energy expenditure, that side of the energy balance equation, and of course, we’re especially interested if any of those steps can be manipulated pharmacologically to allow changing metabolic rates and therefore improve diabetes and obesity.

The reason you have the body mass you have is food intake and energy expenditure, and energy expenditure includes both physical activity and metabolic rates. Your metabolic rates are altered by a variety of things, including temperature, your body’s genetic disposition and your food intake. What causes the current epidemic of obesity is a combination of highly palatable, highly dense foods and people not expending as much energy because they sit around more, and most of us are not as physically active as our ancestors. But that isn’t to say that there aren’t metabolic pathways that could potentially be manipulated to help in the treatment of diabetes.

Healio: What was your reaction when you found out you were the recipient of the 2021 Albert Renold Award from the ADA?

Spiegelman: I was happy and honored because I do value mentorship. I view it as part of my job, not just to get the science done, but to teach the next generation about how to be scientists, how to be effective scientists, how to be ethical scientists, how to be good mentors themselves, and to propagate a culture that includes everybody that has the interest, to be inclusive. Also, to treat people with respect and to share the love and joy for science, and to prepare them for the next stage of their career, to prepare them for scientific independence.

Healio: What do you think will have the greatest influence on your field in the next 10 years?

Spiegelman: I think it is understanding the basic components of energy balance in humans. There’s no question that type 2 diabetes is a disease that, at its root, has an imbalance in energy metabolism — the balance between energy intake and energy output is out of whack. I would like to think the science we’ve done over the last 30 years will lead to medications that get to some of underlying causes. Appetite control, metabolic rate control, diet and exercise, and education are all a very important part of that, without any doubt, but it would actually be wonderful to have some ways to manipulate those pathways and those systems pharmacologically when that is required.

Type 2 diabetes is a worldwide epidemic. Lay people probably don’t realize the human and economic cost of type 2 diabetes. It’s huge. It’s important for our health care systems and for the health of individuals for us to get a grip on that. That’s what I dedicated a large fraction of my career to, and a lot of my colleagues as well. In the next 10 years, finding components of the energy balance system that are amenable to manipulation pharmacologically would be fantastic.