5 Minutes With… Evan P. Nadler, MD

| October 20, 2010

Dr. Nadler is Co-Director, Children’s National Obesity Institute, Children’s National Medical Center, Washington, DC; Principal Investigator, Systems Biology Initiative, Sheikh Zayed Institute for Pediatric Surgical Innovation, Washington, DC; Associate Professor of Surgery, Pediatrics, and Integrative Systems Biology, The George Washington University School of Medicine & Health Sciences

Bariatric Times. 2010;7(10):22

Introduction
Evan P. Nadler, MD, is a pediatric surgeon and researcher at Children’s National Medical Center in Washington, DC. He is the co-director of Children’s National Obesity Institute, and is a principal investigator with the Systems Biology Initiative within the Sheikh Zayed Institute for Pediatric Surgical Innovation, both based at Children’s National. Additionally, he is associate professor of Surgery, Pediatrics and Integrative Systems Biology at The George Washington University School of Medicine & Health Sciences. He performs bariatric surgery on adolescents and works closely with the multidisciplinary team of pediatric specialists in the Obesity Institute. Dr. Nadler’s basic science research focuses on liver fibrosis associated with biliary atresia. His clinical and translational science investigates the systems biology of obesity and the safety and effectiveness of various weight loss procedures in adolescents. The staff of Bariatric Times interviewed Dr. Nadler about his work with adolescents and the goals of his research.

Describe the Sheikh Zayed Institute for Pediatric Research.
The Sheikh Zayed Institute for Pediatric Surgical Innovation is a new institute at Children’s National Medical Center that brings top surgeons and researchers together to improve children’s lives before, during, and after surgery. The goal is to make surgery more precise, less invasive, and pain free. What sets the institute apart from other research centers is a unique model that gives clinicians and researchers unparalleled resources, opportunities, and dedicated time to collaborate in innovative ways that can expedite scientific discovery.

Why is bariatric surgery in adolescents a focus of the Sheikh Zayed Institute?
Obesity is killing America, both literally and figuratively. Not only does obesity play a role in all the major diseases that lead to death, but the financial burden of the healthcare costs of obesity has overwhelmed our economy. Unfortunately, surgery is the only tool we have right now for significant and sustained weight loss. We need to learn more about how it works so that we can apply that knowledge to preventing weight gain in the first place. Furthermore, we need to know why some people are more successful than others following surgery. Surgery is a model through which we can explore the mechanisms at play in both weight gain and weight loss. Our bariatric surgery work is part of the Institute’s Systems Biology Initiative, a multidisciplinary effort to understand how distinct cells, tissues, and organs work together in disease and surgical interventions.

Why are adolescents a good model for studying treatments for extreme obesity?
An overall driving hypothesis in our research is that the ability to identify genetic determinants of risk is greatly enhanced by using younger populations. To say it simply, adolescents are a good model for studying obesity because they generally have fewer or less severe diseases associated with their obesity since there has been less time to be affected by poor lifestyle habits. Thus, if you are studying the genetics in an adult group of patients you may really be studying the genetics of type 2 diabetes or hypertension since most adults with obesity have these illnesses as well. In adolescents, you will find comparable patients with obesity with only insulin resistance and thus the root genetic effects driving cardiometabolic disease will be easier to detect. Similarly, the pathways at play in extreme weight loss in adolescents will not be affected by diabetes or hypertension and will be more representative of potential pathways in extreme weight gain.

How is the Institute advancing research on bariatric surgery in adolescents? What are your goals?
Working with genomics expert Monica Hubal, PhD, we have two studies underway through the Institute. The first looks at the genetics of weight loss surgery. We want to identify specific genetic variations in an individual that can predict success or failure for certain interventions. The overall goal is to develop personalized medicine approaches to selecting an obesity treatment based on a patient’s genetic profile. In the second study, we are examining muscle, liver, and fat tissue samples in patients before and after weight loss surgery to identify the molecular pathways important for successful extreme weight loss. The hypothesis is that the same pathways will be important for weight gain, and once they’re identified, you can target them with prevention strategies and therapies to hopefully make surgery obsolete.

Most people believe that social and environmental factors determine weight loss success or failure. What is your opinion?
If weight gain is hereditary, why not weight loss? Social influences are typically the same before and after surgery and are generally the same for all patients who undergo surgery. Thus, there is likely a better explanation for why some patients are successful at losing weight after surgery and some are not. Beyond that, extreme lifestyle changes work for very few people and they are impractical for most. Most people do not have the time or money to exercise six hours a day or eat a highly specific, restricted diet. That is why it is important to identify the underlying genetic factors and pathways that influence weight gain and loss, so that we can devise better ways to prevent weight gain and improve weight loss.

What are the unique advantages the Institute provides for your work?
At a time when research grant funding is shrinking, the Institute, thanks to a $150 million gift from the government of Abu Dhabi, provides unparalleled opportunities and resources to pursue innovative ideas and accelerate discovery. We have the capacity to turn what normally would be a 7 to 10 year project into a two-year project. We have infrastructure you will not find many other places. For example, we’ll soon be the first children’s hospital with a Single Molecule Real Time next-generation sequencing machine to enhance epigenetic research. With current studies of obesity, we understand about 10 percent of the genetics involved. The use of next generation sequencing provides an opportunity to understand a great deal more.

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