November 15, 2016 | Patti Wieser
Adriana Tremoulet, MD
Her intentions for a career in medicine were shaped early, as a child. She always knew her focus would be pediatrics. While completing her master’s in clinical research, one of her mentors introduced her to Kawasaki disease. Today, Adriana Tremoulet, MD, is the associate director of the Kawasaki Disease Research Center at UC San Diego. In this role, she cares for nearly 1,500 children with Kawasaki disease in San Diego County and an additional 90 children a year hospitalized at Rady Children's Hospital-San Diego. Kawasaki disease (KD), an acute, self-limited vasculitis in childhood, is the leading cause of acquired heart disease in children in the United States and Japan.
In 2013, Tremoulet, a pediatrician and pediatrics researcher, received support from the Clinical and Translational Research Institute (CTRI) for a pilot project to study why some children with KD do not respond to standard treatment. Generally, KD children receive an antibody infusion called intravenous immunoglobulin (IVIG), an expensive therapy that must be administered in a hospital setting and is not available or affordable in many areas of the world. Tremoulet’s research led to new understanding – and new hope for children with KD and their parents. Results from the pilot were published in a 2013 Public Library of Science (PLOS One) article she co-authored titled, “Treatment Response in Kawasaki Disease Is Associated with Sialylation Levels of Endogenous but Not Therapeutic Intravenous Immunoglobulin G.”
“My CTRI project focused on immunoglobulin G sialylation in patients with treatment-resistant Kawasaki disease. We looked at a particular component of IVIG and found it actually had less to do with the IVIG we give the children and more to do with their endogenous sialylation of their own immunoglobulin in responding to therapy,” said Tremoulet said. Immunoglobulin is a type of antibody and sialylation is an immunity regulatory process.
Her pilot project goals were to evaluate alternative treatment and gain a better understanding of the anti-inflammatory mechanism of the disease. “My passion lies in improving our knowledge about the drugs we use to treat pediatric conditions and expanding our ability to use different drugs,” said Tremoulet, who has a background in infectious diseases and pharmacology. The pilot and subsequent research have led to new possibilities for a much more affordable, safe product that can be used worldwide, as well as a very directed therapy for KD based on identifying important parts and function of IVIG.
For the past decade, Tremoulet has concentrated on pediatric clinical trials after earlier stints doing the gamut of chemistry and biology labs. She performs much of her research in a collaborative setting. She works with UC San Diego researcher Jane Burns, MD, and has forged a successful collaboration with Alessandra Franco, MD, PhD to tackle KD and other inflammatory and autoimmune diseases. Tremoulet and Franco have offices next door to one another in the Basic Science Building and have jointly published eight papers in professional journals.
The Tremoulet-Franco collaboration merges Tremoulet’s background in clinical trials and pharmacology with Franco’s basic science expertise and knowledge of the clinical component.
“Our collaboration has really mapped out the immune response in KD. We have a clinical back and forth that makes the work fluid and very exciting, with results that are truly translational,” Tremoulet said. “We literally go from the bench to the bedside and from the bedside to the bench. We draw blood from a child in the bedside, bring that blood to Dr. Franco’s lab, and she spins and isolates the cells and characterizes the immune regulation that is occurring in that child, and then monitors how the immune panel looks based on the treatments.”
While key for KD, the research is applicable to a broad range of inflammatory and autoimmune diseases. “What we’re studying is not specific to just KD. We are trying to develop models that are applicable across the board and provide readouts for clinical trials with very relevant data about the usefulness of a drug,” Tremoulet said.
Tremoulet, associate professor of clinical research in pediatrics at UC San Diego and associate director of clinical research at Rady Children’s Hospital and the author or co-author of more than 60 publications in professional journals, acknowledged how CTRI enabled her research.
“The CTRI support was critical to the success of our pilot project to understand why children with Kawasaki disease are resistant to initial treatment. Through this support we have discovered a genetic predisposition for this, which could ultimately lead to better therapeutic approaches to children with KD,” said Tremoulet.