Fascinating [Circadian] Rhythm: Q&A with Joseph Bass, MD, PhD

Joseph-T.-Bass_Headshot_GreepAward

As one of the world’s leading experts in circadian biology and endocrinology, Joseph Bass, MD, PhD, was an obvious choice for the Endocrine Society’s 2023 Roy O. Greep Outstanding Research Laureate Award. He talks to Endocrine News about the award, his mentors along the way, and how he became so enamored with the science behind sleep.

For many wanting to lose weight, a common recommendation involves restricting those late-night raids of the refrigerator. Joseph Bass, MD, PhD, is a researcher working to unlock the specific reasons why these restrictions work.

In January, Bass was selected as one of the Endocrine Society’s 13 leaders in the endocrinology field as winners of its prestigious 2023 Laureate Awards. He was presented with the Roy O. Greep Award for Outstanding Research that recognizes meritorious contributions to research in endocrinology.

Bass is the Charles F. Kettering Professor of Medicine and chief of Endocrinology, Metabolism and Molecular Medicine in the Department of Medicine at Northwestern University Feinberg School of Medicine, Chicago, Ill. He earned both his MD and PhD at the Medical College of Pennsylvania and completed fellowships in endocrinology as well as Molecular Biology. Since joining the faculty at Northwestern at the start of 2000, Bass has become one of the world’s leaders in circadian biology and endocrinology. In his most recently published research in last October’s issue of Science, Bass and fellow researchers uncovered the mechanism behind why eating late at night is linked to weight gain and diabetes.

Endocrine News spoke with Bass to learn more about his life’s work as well as how he likes to unwind outside the lab. Spoiler alert: You may catch him and his trumpet on the Chicago’s nighttime jazz scene.

Endocrine News: Can you share your thoughts of when you first heard the news about being named for the Outstanding Research award?

My original interest was in understanding, in a very broad sense, the molecular basis of molecular physiology from the tradition of studying and cloning insulin, etcetera. From my vantage point, when I was in medical school, endocrinology seemed to be one of the areas in which there was an integration of molecular concepts early on.

Bass: I guess a mixture of surprise and gratitude.Surprise in that it was unexpected and that there are many qualified people, and gratitude in the sense that the award provides recognition to a field more than a person, in my view. It’s a way of indicating that the field has advanced what we understand about endocrine systems and endocrine disease.

EN: Your work in discovering how disruptions to circadian rhythms and body clocks affect our metabolism is well known. Can you talk about the implications of your findings?

Bass: Our work really was early in recognizing that the molecular machinery controlling internal clocks, biologic timing, also plays an essential role in brain and peripheral tissue systems that regulate body weight and metabolism, and many other endocrine processes.

I would add that an unexpected implication of our work has been to understand the cause of metabolic disorders that occur under conditions in which the internal clock cycles are misaligned with the external light/dark environment, meaning the normal time when the sun rises and when it is natural for us to wake up. When the coincidence between the environmental light cycle and internal endocrine cycles is disrupted, or when cycles in different tissues are disrupted, then a variety of endocrine disorders ensue. By virtue of molecular advances in understanding rhythms within different cell types, we have come to understand how clocks program tissues to function in different ways at different times of the day and night. We can now view the coordination amongst systemic clocks as a key to health, not only regarding the brain and its response to light, but also more broadly throughout the body.

This work began serendipitously when we started to systematically study the very first animals in which the core genes for the clock had been disrupted. While the core molecular clock was discovered because of its role in controlling 24 hours of behavior in flies, availability of circadian mutants in mice enabled showed that clocks are vital, central regulators of our metabolic and neuroendocrine systems.

EN: How did you find yourself delving into this type of research?

Bass: Well, my original interest was in understanding, in a very broad sense, the molecular basis of molecular physiology from the tradition of studying and cloning insulin, etcetera. From my vantage point, when I was in medical school, endocrinology seemed to be one of the areas in which there was an integration of molecular concepts early on.

During that period when I was training, I was aware of the application of genetics, which I found fascinating, to understanding physiology, and with the discovery of energy regulators with the cloning of leptin, and then also with forward mutagenesis leading to the discovery of the clock genes, these were very intriguing developments to me.

And by coincidence, my first job was at Northwestern, and I was having conversations with Joe Takahashi, who had discovered by positional cloning the first genes for the clock in mammals, and it really was this coincidence and the background I had in understanding how molecular approaches can advance our understanding of endocrine systems. And the confluence of that background and this new problem, that these circadian mutant animals that were studied because of their sleep/wake behavior, might also exhibit metabolic disorders. These were early days, because it was around the late ‘90s when the first circadian experimental models became available to study physiology.

EN: Who have been your biggest mentors or collaborators who’ve helped towards your goals?

Bass: I mentioned Joe Takahashi earlier and also Fred Turek and Ravi Allada, colleagues at Northwestern who welcomed me to circadian research.More recently, Nav Chandel, Milan Mrksich, Talia Lerner, Lisa Beutler, and Grant Barish have each been close collaborators. Grant and I have a team. He came here from Ron Evan’s group with strong training in nuclear receptor transcription and genomics. Northwestern has fostered a supportive environment and enabled our work to grow as our questions have expanded.I have thrived at Northwestern due in large part to the many stimulating colleagues and trainees.

Our work really was early in recognizing that the molecular machinery controlling internal clocks, biologic timing, also plays an essential role in brain and peripheral tissue systems that regulate body weight and metabolism, and many other endocrine processes.

EN:  When you’re not working in the lab, what’s your favorite place to go to find your work/life balance?

Bass: My major thing outside of research is really music, and it has been ever since I was a kid. I went to music school before I went to college, and I played throughout medical school. There was a long hiatus during training, but more recently, I’ve been playing again and that’s extremely rewarding to me. It’s something I grew up with, and it is an endeavor, I wouldn’t call  a hobby … it’s more than that.

EN: It definitely sounds like more than a hobby!

Bass: Yeah, I play the trumpet and I play in a few groups here. I just started picking up jazz at DePaul and there’s a place called the Music Institute of Chicago near me. I’m playing there to learn and extend my repertoire in jazz.

Fauntleroy Shaw is a freelance writer based in Carmel, Ind. She is a regular contributor to Endocrine News.

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