Deborah Muoio, PhD is the George Barth Geller Distinguished Professor of Cardiovascular Disease, professor of Medicine, and professor in Pharmacology and Cancer Biology at the Duke School of Medicine. She serves as the Associate Director of the Duke Molecular Physiology Institute (DMPI), as a member of Sarah W. Stedman Nutrition and Metabolism Center, as well as a member of the Duke Cancer Institute. Dr. Muoio is an internationally recognized leader in the fields of diabetes, obesity, exercise physiology, and mitochondrial energy metabolism, having published more than 120 papers in top scientific journals such as Cell, Cell Metabolism, Circulation, Circulation Research, Diabetes, and JCI Insight.
How have you decided to become a scientist focused on what you do now?
Deborah Muoio, PhD: It took a while before I knew exactly what I wanted to do. When I was in high school, I always liked science and math, and I had an excellent biology teacher who nudged me in that direction, but I did not have a clear career vision or obvious passion.
I was very active in a variety of sports, which sparked my interest in understanding human performance, exercise physiology, and sports nutrition. When I was an undergraduate, I focused on physiology, food science, and nutrition as a curriculum. After my undergraduate studies, I went to work for the food industry, for one of those companies that produces unhealthy foods. This gave me a valuable perspective. When I was about 22 years old, I was trying to convince this food company to improve the nutritional quality of their products, but they were clearly uninterested in that mission. I decided then to go back to graduate school for a master's degree in exercise physiology and nutritional biochemistry. I had intended, with my master's degree, to work as a nutrition counselor for college athletes, which I did for a short period. But I was not very good at that job, because I didn't want to simply advise athletes and recommend diets to enhance their physical performance. Rather, I enjoyed teaching them about the physiology – exactly how exercise training reprograms energy metabolism and how the various organ systems work together to achieve peak muscle performance – topics that the athletes were not so interested in. I finally realized that I had a passionate for physiology and metabolic research and understood that it was the time to pursue a PhD.
“The boys would tell me “no, girls don't play these sports!” and I would respond “Just watch me!””
Did you have to fight the perception that women have soft skills and cannot be good scientists?
Deborah Muoio, PhD: I was extraordinarily fortunate to have many wonderful mentors, most of whom were men because (at that time) there were so many more men in science. Although all of my mentors were super supportive, there were certainly others in the broader community who were not as encouraging. I got somewhat acquainted with certain attitudes about women when I was a young female athlete. For example, I would often invite myself to play football and baseball with the boys, who would tell me “no, girls don't play these sports” and I would respond “just watch me.” My father made it clear that sex doesn't matter, and always encouraged me to pursue whatever interests I had. I think these kinds of experiences, which I had when I was young, stayed with me and motivated me to compete in a male-dominated profession.
My earliest exposure to metabolic research was as a master’s student at SUNY Buffalo, where I studied exercise physiology under the mentorship of Dr. David Pendergast. “Dr. P” gave me the opportunity to present our work at several scientific meetings. After that experience, I was hooked, and moved to UNC for further training as a PhD candidate. At UNC, my graduate advisor, Rosalind Coleman, was a strong, brilliant, amazing woman who served as an inspiring role model. When I was a postdoctoral fellow, I was co-mentored by Bill Kraus at Duke and Lynis Dohm at East Carolina University. Both were highly encouraging and gave me the freedom to pursue my research interests with great independence and autonomy. One of the most influential people for my career development and advancement was Chris Newgard, the director of the Duke Molecular and Physiology Institute. From the day he hired me as Assistant Professor at Duke and throughout the past twenty some years, he has been an unrelenting advocate and champion for me. In aggregate, I was very fortunate. I benefited from a variety of generous and fabulously supportive mentors.
Yes, you were fortunate. But I also think that this speaks to how you chose your mentors. So, I wanted to ask you whether you have advice for trainees about how to choose a mentor to avoid bad mentorship.
Deborah Muoio, PhD: This is an excellent point. I did think and plan carefully at each step and took responsibility for all the decisions I made throughout my career. I interviewed my mentors to learn about their expectations and I explained to them what I hoped to gain from my training experiences. It also helped me that I took a break from school after my undergraduate studies. I then returned to graduate school with more maturity, experience and confidence when approaching my mentors. I absolutely agree with you that the process of selecting good mentors and avoiding bad mentorship should be an active one. Trainees should take an active role in evaluating prospective mentors, not only by talking and meeting with them, but also by speaking with their current and former trainees. Another path for trainees to improve mentorship is to seek out multiple mentors early in their career, including some that are outside of their immediate lab and/or department, because there could be times when advice is needed from someone who is not their immediate supervisor.
“I ask trainees to avoid expressing deep disappointment with negative results.”
What is your mentoring style?
Deborah Muoio, PhD: I am engaged and deeply committed to helping trainees advance their skills and meet their goals. I like to be involved in every stage of the research, ranging from conceptualization, experimental planning, data interpretation and visualization, and writing. I try not to micro-manage: In general, I let people come to me when they're ready and when they have data or other topics they would like to review and discuss. However, if the line goes silent for too long, I will initiate some chatter. Our lab uses Slack as a communication tool, which I have found to be quite effective–much more so than email. We also use electronic notebooks and I ask all lab members to post monthly activity reports so I can keep tabs on our progress and assess potential barriers. I also like to take a team-based approach to science. There's a wealth of experience, expertise, and talent in my lab and the DMPI. We routinely come together as a team to plan experiments, discuss puzzling findings, and troubleshoot technical problems. I encourage people to disagree respectfully if they have conflicting opinions on experimental design or different interpretations of the data. I try to create a culture in which people are comfortable challenging one another. This is how we get better. It is very important to create a culture and an environment where people feel like their opinions are valued and where they can disagree with the PI. I also ask trainees to avoid expressing deep disappointment with negative data. When the results are at odds with our hypothesis, it means that we are learning. When early-stage researchers feel like they're pushed into a corner to produce a highly desired result, it is not only bad for their career development, but also damaging to science in general.
What is the most common issue that you see in your role, as the head of the Duke Authorship Dispute Board?
Deborah Muoio, PhD: We have reviewed more disagreements about authorship order than who is included as an author on a paper. This is not surprising because publications are a primary metric of performance in academia. Naturally, people want to be recognized appropriately when they believe they've taken a leadership role in a project and the corresponding paper. The best way to avoid misunderstandings is to discuss the topic of authorship early and often. It really comes down to open communication from a very early stage. Also, communicating often is key, because the manuscript rarely looks the same at the end of the process as it does in the beginning.
“Transparency is key. It is important to acknowledge all the people who played a role in shaping the manuscript, even if they do not qualify for authorship.”
A question that we received in our roundtable is how to discuss authorship roles early when you are the only one who cares and there is a lot of power imbalance? Do you have any advice on handling this kind of situations?
Deborah Muoio, PhD: In my experience, faculty are very busy, research moves fast, and having a conversation about authorship might not be at the forefront of the PI’s mind at the earlier stages of a project. But, when the junior researcher asks, “can we talk about what the expectations are to be included as an author?” the PI should be receptive. I think in most cases they will be. If the lab director seems to be avoiding conversations about authorship, that's a problem. One next step could be to seek counsel from a senior person at the departmental level. As another option, a junior researcher could ask the chair of the department to organize a workshop or seminar covering authorship issues, which would provide opportunities to open discussions on some general topics that might be difficult or uncomfortable to raise in a one-on-one setting.
Another question we received in our roundtables is related to staff members being overlooked more often than faculty from authorship.
Deborah Muoio, PhD: I am not sure I agree with the term overlooked. Earning and granting authorship is largely about intellectual and scholarly contributions. So, executing the mechanics of any given job in the laboratory does not necessarily qualify someone for authorship. For example, a staff member who does a lot of mouse work: breeds the animals, generate cohorts for different studies, does genotyping, but does not have a direct role in advancing a specific project and preparing the paper–while this person is certainly valuable to the team, he/she has not contributed in a scholarly manner. In other cases, there are staff members who are quite intellectually engaged in guiding the science, and therefore should be included in the author list. If research staff members are interested in earning authorship, they should communicate their goals to the PI and ask if there might be opportunities to contribute to a project at a higher intellectual level.
We learned in our roundtables that technical writers are used widely in some disciplines. Some people have trouble walking the line between listing them as authors and not mentioning them at all.
Deborah Muoio, PhD: It is important to distinguish between professional writers who have no role in the science, but are hired to write some portions of the manuscript, and those who are connected to the research, such as an industry partner, and who might influence the narrative and benefit from research but are not listed as an author. Transparency is key. It is important to acknowledge all the people who played a role in shaping the manuscript, even if they do not qualify for authorship. These types of contributions should be disclosed in the acknowledgments section of the paper.
Could you tell us what your current research project is about?
Deborah Muoio, PhD: The overarching theme of our research centers on understanding the interplay between lifestyle, health outcomes and risk of metabolic diseases, such as obesity, type 2 diabetes, heart failure, and cardiovascular disease. We want to understand why some lifestyles – a nutritious diet, habitual physical activity - seem to promote overall health and lower risk of diseases, while other lifestyles accelerate the aging process and increase the risk of metabolic diseases. The mechanistic aspects of our work focus largely on mitochondria, which are commonly known as the “powerhouse of the cell”. These tiny organelles act as biological engines that convert energy harnessed in foods we eat to a form of energy that our cells use to perform a wide variety of tasks. This means that mitochondria help the heart to beat, and the muscles to contract, and the neurons to fire. There is pretty solid evidence that as we age, the machinery inside those mitochondria lose power. And, if the mitochondria aren’t functioning properly, there is a very good chance that the cells they are supporting won't function properly either. For this reason, many scientists have proposed that mitochondrial failure contributes to the progression of chronic diseases. Our research aims to understand why mitochondrial performance tends to decline as we age and in response to poor lifestyle habits. We also hope to identify strategies that can slow the rate of this decay – for example, regular exercise and intermittent fasting. Ultimately, we aim to tailor specific lifestyle interventions to improve mitochondrial health, and to help others develop drugs that can target these same pathways.
You are also studying the impact of intermittent fasting on health outcomes…
Deborah Muoio, PhD: Yes, in recent studies we have been investigating how the body responds to a dietary regimen that involves extended periods of fasting. This is commonly known as intermittent fasting, alternate day fasting or time-restricted eating. Mounting evidence suggests these regimens can confer many health benefits. While most of this evidence comes from work in animal models, a growing number of human studies are producing some promising results.
We studied time-restricted feeding in mice and found that a regimen that permits only 6 hours of food access per day for 4 days each week improved blood sugar control, reduced body fat, enhanced mitochondrial efficiency, and increased muscle mass. In sum, we observed a lot of really exciting improvements in the overall health of the mice. This was consistent with other reports in the literature. One unique aspect of our project is that we identified a crucial role for a specific type of fuel, called ketones, in mediating these health benefits. Ketones are generated and released into the blood by the liver during a fasting period. When we are not eating, these liver-derived ketones help to fuel mitochondrial energy production in organs such as the brain, heart, and skeletal muscles. Ketones are a very cool example of how different organ systems work in concert to allow the human body to cope with physiological stresses, like prolonged fasting and endurance exercise.
Why intermittent fasting does help us to lose weight?
Deborah Muoio, PhD: When we are not eating sugar and other forms of carbohydrate, our body uses lipids (fats or fatty acids) as a primary source of energy. Most of that lipid is warehoused in the adipose tissue, which releases stored fatty acids into the blood during periods of food restriction. This process, called lipolysis, promotes weight loss. However, not all tissues can burn fatty acids efficiently. To overcome this problem the liver converts fatty acids to ketones, thereby providing an alternative fuel that is then delivered to the brain and other extrahepatic tissues. Some scientists working in this field have speculated that ketones serve as “super fuels” that have unique bioenergetic properties. Our team is interested in testing that concept. Is there something special about ketones that is required to get the benefits of intermittent fasting?
The textbooks teach us that ketones are critical for the brain because neurons are not good at using fat as a fuel. We wanted to know if tissues that can burn fatty acids, like heart and skeletal muscle, also benefit from ketones. To address this question, we generated a mouse model in which the ketone-burning pathway was disrupted specifically in cardiac and skeletal muscles; The answer was – yes, we showed for the first time that ketone use by these tissues was indeed required to gain the full benefits of the time-restricted feeding regimen. The next critically important question is “Will these results translate to humans?” As a rule, we try to be cautious about over-interpreting data from animal research. This is one study and one mouse model, but the findings are very exciting. We are now looking towards opportunities to partner with clinical investigators at DMPI to perform human studies.
How the fasting regimen works as our body does adapts to it? Do we lose less weight then?
Deborah Muoio, PhD: One fascinating outcome of our study was that within just a couple of weeks, we saw unambiguous evidence that the mice were quickly adapting to the new feeding regimen. When access to food is removed from naïve animals, their blood glucose falls dramatically, ketones spike and the mice lose lean body mass, which together indicate that prolonged fasting is stressful when animals are not accustomed to the routine. After repeated exposures to overnight fasting, the entire system adapts, and the adapted mice were more metabolically resilient. They were better able to maintain blood glucose levels and they preserved lean body mass at the expense of losing more adipose (fat) tissue. Over time, the system does appear to become more energy efficient and therefore the rate of weight loss tapers. Still, even without substantial weight loss, there is a very good chance that interventions involving time-restricted eating and/or regular exercise are working to enhance metabolic health behind the scenes. In other words, there are many health metrics (beyond the number on the scale) that are likely to improve, including blood sugar control. Unfortunately, these outcomes are not routinely monitored and therefore the average person gets discouraged when weight loss hits a plateau.
Can intermittent fasting lead to disordered eating?
Deborah Muoio, PhD: This is a good question that the field needs to address. It is not my area of expertise, but I know that there are some individuals that could have vulnerabilities.
Is the intermittent fasting diet better than the no added sugar diet?
Deborah Muoio, PhD: Both the animal data and human studies say that genetic architecture matters; meaning that the optimal dietary plan depends on genetic background. So, personalized medicine, including customized diet and exercise prescriptions, appears to be the answer. There's still a lot of work to be done to understand how we can develop the best individualized approaches. Nonetheless, most Americans would benefit from eating less sugar. Unfortunately, our food supply is filled with heavily processed, calorically dense foods that are high in sugar. Many food manufactures stick with this formula because our brains like sugar and the main goal of industry is to sell more product. Not too many people will have a bite or two of a snickers bar and say, “I'm perfectly satisfied.” Instead, our neurons light up and we crave more sweets. Efforts to reduce sugar consumption are not easy. In my opinion, the best strategy is to exercise discipline at the supermarket by not buying unhealthy foods, that way they will not be easily accessible and irresistibly tempting at home.
What advice do you have for college students and adults who try to have a healthy diet?
Deborah Muoio, PhD: Stay away from sugary, highly processed foods and instead eat natural foods. Eating fresh foods, fruits, nuts, vegetables, and greens affords many benefits for weight control, glucose control, blood lipid profiles, the microbiome, and brain health. The challenge for many people is that eating healthy can be more expensive and more time consuming. Food companies make it very affordable and convenient to eat their highly processed, nutrient-poor products. Nutrition counselors, as well as many good books and podcasts on the topic, can provide guidance on how to transition to a healthy diet in an affordable and less laborious way.
Do you think that scientists could in the future persuade the food industry to reduce producing processed, sugary foods?
Deborah Muoio, PhD: Persuading the food industry to do things differently will most likely require public pressure. Scientists should be advocates for a healthier lifestyle and they should continue to provide evidence-based guidelines; but, in my view, the food industry is unlikely to change course unless their profits start suffering. Therefore, experts in this field should help educate the public and work to promote policies that make nutritious foods and healthier lifestyles more accessible to more people.