TAMEST Profile: Ralph DeBerardinis, M.D., Ph.D. (NAM), UT Southwestern Medical Center
TAMEST Member and Mary Beth Maddox Award and Lectureship Committee Chair Ralph DeBerardinis, M.D., Ph.D. (NAM) serves as Professor and Director of the Eugene McDermott Center for Human Growth and Development, and Professor in the Children’s Medical Center Research Institute at UT Southwestern Medical Center.
A world-renowned expert in metabolism, Dr. DeBerardinis’ lab studies the role of metabolic perturbations in human diseases, particularly pediatric inborn errors of metabolism and cancer. His research is tightly integrated with clinical activities in medical genetics, oncology and radiology, providing seamless opportunities to identify metabolic anomalies in patients and then study them in the laboratory.
Dr. DeBerardinis joined the faculty of UT Southwestern in 2008 and the Children’s Medical Center Research Institute at UT Southwestern in 2011. In 2019, he received the Edith and Peter O’Donnell Award in Medicine for studying how altered metabolism leads to diseases in humans. In 2020, he was elected to the National Academy of Medicine for his work in cancer metabolism, which has changed our understanding of how tumors reprogram metabolic pathways to maximize energy production and growth.
Dr. DeBerardinis serves as the Committee Chair of the Mary Beth Maddox Award and Lectureship at TAMEST, which recognizes women scientists in Texas bringing new ideas and innovations to the fight against cancer. TAMEST connected with Dr. DeBerardinis to learn more about his research in metabolism, leadership at TAMEST and the importance of recognizing cancer researchers in Texas.
You are a pioneer in the study of how altered metabolism leads to human disease. Please describe your research path.
My career in metabolism started slowly. I was not a very good biochemistry student in college or medical school. I had a hard time seeing the physiological relevance of the metabolic pathways we had to memorize. I was better in genetics, so I entered my research training with the intention of doing a Ph.D. in a genetics lab. I didn’t realize then how closely related metabolism is to genetics, but I would soon find out.
My Ph.D. advisor at the University of Pennsylvania was Haig Kazazian Jr., M.D., an excellent physician-scientist who had trained in pediatrics and medical genetics. Dr. Haig encouraged me to do the same. During my clinical training, I started seeing patients with inborn errors of metabolism, diseases caused by mutations in metabolic enzymes and related proteins. Suddenly it was impossible to miss the importance of these pathways because I could see all the problems that arose when even a single enzyme wasn’t functioning properly. I was shocked to find out that there are over 1,000 inborn errors of metabolism, making them the largest group of genetic disease in humans.
That experience hooked me on human metabolism, and I was determined to work on metabolism during my postdoctoral research training. I wanted to discover new ways to turn metabolic pathways on and off. But at that time, it was hard to find labs focusing on metabolic pathways per se. Fortunately for me, Craig Thompson offered me a spot in his lab. Craig was interested in the idea that tumors activate growth-promoting metabolic pathways in order to grow.
I worked with Craig from 2004-2008, studying how growth factors and oncogenes cause cells to take up nutrients and use them to produce energy and building blocks for growth. When I started my own lab in 2008, all my initial research was on cancer metabolism, which luckily for me had become popular and fundable. A few years later, when the lab gained momentum, we started studying inborn errors of metabolism, too. These days, half of my lab studies cancer and the other half studies inborn errors. But everyone works together – you can learn a lot about cancer metabolism by studying inborn errors, and vice versa.
You are also the Chief of the Division of Pediatric Genetics and Metabolism at UT Southwestern. What made you decide to focus on pediatrics specifically?
Most of my physician-scientist friends went into internal medicine, but I found childhood diseases more interesting. And I liked working with families, which is an important part of pediatrics.
I was also compelled by the idea that successful treatments in babies and children could have positive effects for many decades – literally changing the entire arc of a patient’s life. I was also inspired by the rapid expansion of newborn screening for inborn errors of metabolism, where early detection translated into life-saving treatments for diseases that had until then been associated with unavoidable morbidity and mortality. It was an exciting time to work in pediatrics and especially medical genetics.
In 2019, you were awarded the Edith and Peter O’Donnell Award in Medicine for your work in cancer metabolism and how it related our understanding of how tumors reprogram metabolic pathways to maximize energy production and growth. What did the recognition mean to you and your career?
By 2019, my lab had spent over 10 years working on cancer metabolism. During that period, the cancer metabolism field had become large and competitive. The Edith and Peter O’Donnell Award in Medicine meant so much to me because it substantiated the impact our work was having on the field. Having our work recognized publicly by TAMEST was a proud moment for me, my lab and my family.
The award also had a positive effect on our science. Our approaches to studying cancer metabolism are quite different from most other scientists working in this space. Because we study tumor metabolism directly in patients rather than in mice and cultured cell lines, it takes a lot of patience and funding to carry out the experiments. There were many days when I would wonder whether what we were learning was worth all the effort. I felt that the O’Donnell Award in Medicine indicated a vote of confidence that we were on the right track, and it encouraged us to keep asking tough questions in the most rigorous and relevant way.
In 2020, you were elected to the National Academy of Medicine and became a member of TAMEST. Especially as a former TAMEST award recipient, what did becoming a member of the NAM and TAMEST mean to you?
My mentors and scientific heroes are members of the National Academies and TAMEST. Joining their ranks was an incredible honor. I also see it as a responsibility to meet the highest standards of scientific integrity and rigor, to mentor the next generation of leaders, and to do whatever I can to communicate the importance of science and evidence-based medicine to the public.
What makes you most passionate about your work?
Nothing beats seeing new data and realizing that you’ve made a discovery. There’s just nothing like it. I started my research career as a college junior working in a microbiology lab and I will never forget the first time an experiment produced a result that answered a question and moved the project forward.
I realized on that day how incredible it would be to have a career in research, and I’ve been dedicated to it ever since. I’m also inspired by the opportunity to mentor trainees in my lab, to see them experience the jolt of discovery and help them move forward in their own careers. And I value working with patients as partners in research. Much of our work involves direct interactions with patients, and it’s an inspiration to meet people who want to participate in research projects.
You serve as Committee Chair of the Mary Beth Maddox Award and Lectureship, which honors innovative women cancer researchers in Texas. Why did you agree to volunteer your time to help lead this award committee?
Texas has so many talented scientists studying cancer, particularly at the junior faculty level. For almost 15 years, state-based funding through CPRIT has helped us recruit the best cancer researchers in the world to Texas.
The greatest impact has been in recruiting young, first-time faculty, and this has had such a positive impact on the kinds of outstanding cancer science we now see across the state. I like the fact that the Mary Beth Maddox Award and Lectureship seeks to identify and honor the achievements of younger scientists. There’s so much talent to choose from, including the many women working in cancer research who are eligible for this award.
Why is honoring up-and-coming women in cancer research important to do?
We need as many voices and interests in cancer research as possible. Many factors contribute to the challenges women face in academic science, and these factors begin to exert themselves early in life.
That makes it so important to highlight and celebrate the success of outstanding women researchers. I’m proud that TAMEST is doing this through the Mary Beth Maddox Award and Lectureship. The lectureship component, in which the awardee speaks at several Texas institutions, is valuable because it supports scientific networking across the state, and hopefully amplifies the message that TAMEST prioritizes honoring the contributions of up-and-coming women in cancer research.
You’ve received many awards and honors in your career. Please talk about the importance of mentorship for early-to-mid-level faculty and researchers.
Part of what makes leading a research lab challenging is that it requires skills in so many different areas. By the time we launch our independent labs, we’ve begun to master some of these: scientific rigor, experimental design, determination, resilience, etc.
But this only scratches the surface of what is needed to excel as a scientist. You also have to learn how to recruit people to your group, inspire them to be great, manage a budget, communicate your ideas to funding agencies and become a mentor yourself. Most of us do not intuitively know how to do all of these things – I know I didn’t.
I received a great deal of help and advice in all these areas from senior faculty mentors in my first few years at UT Southwestern. This was such a positive factor in my scientific development, and the generosity of the senior faculty is one of the things that makes UT Southwestern great. I currently mentor about a dozen early- and mid-career faculty in research and clinical medicine, and this is among the most rewarding things I do.
Why do you live and work in the state of Texas?
I came to UT Southwestern in 2008 because of its long history of discovery in genetics and metabolism, my two primary areas of interest. I’ve stayed ever since because of the incredible scientific community at my institution and because of the blue-sky attitude about innovation here and around Texas.
This is a state with the resources and appetite to do big things. I arrived two years before CPRIT was launched, so I’ve seen first-hand the transformative effect of that program on the quality and breadth of cancer research around Texas.
The emphasis on high-risk, high-impact research in Texas is hard to find elsewhere. I also live in a fantastic and affordable neighborhood in South Dallas, and my daughter is a 7th grader in an incredible middle school from the Dallas public school system. It’s an easy place to live.
