Dr. Kendra Francis-Stream, has been awarded a Pilot and Feasibility Award through the UW Nutrition Obesity Research Center for her project entitled: “Mechanisms of exclusive enteral nutritional therapy in Crohn’s disease.”
Dr. Francis-Stream received a BA at Pomona College, CA before completing her MD at the University of Washington. She subsequently completed her residency and fellowship at Seattle Children’s Hospital and the University of Washington within the Department of Pediatrics. Dr. Francis-Stream was recently promoted to an Assistant Professor within the Department of Pediatrics and the Division of Gastroenterology and Hepatology. She is a pediatric gastroenterologist with clinical expertise and a research interest in the pathophysiology of pediatric inflammatory bowel disease.
Project description: Intestinal bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn’s disease (CD), are increasingly common chronic inflammatory conditions of the gastrointestinal tract that are associated with significant morbidity and economic cost. While immunosuppression therapies can promote mucosal healing and lead to clinical remission, exclusive enteral nutrition (EEN) is also safe and effective treatment for CD without need for immunosuppression, although the underlying mechanism(s) remain to be elucidated. An important part of intestinal barrier function is the intestinal extracellular matrix (ECM). This proposal will detail the effect of EEN on an important component of the ECM, chondroitin sulfate and dermatan sulfate glycosaminoglycan (CS/DS-GAG) chains. In support of this, recent work from the Francis-Stream laboratory has shown pathological alterations in the CS/DS-GAG composition in the ileum of patients with active CD, but have yet to detail how these alterations may be affected by EEN therapy. To test this, studies in Aim 1 will compare the, the CS/DS-GAG composition after EEN vs. corticosteroid induction therapy in patients with CD. Studies in Aim 2 will use a preclinical model of CD to determine whether oral supplementation of CS/DS-GAG components will improve disease outcomes with or without EEN therapy. This work will be supported by the Nutrition Obesity Research Center Energy Balance Core, the Clinical and Translational Research Services Core and the Biostatistics Subcore. The overarching hypothesis is that EEN will induce clinical remission by normalizing the imbalance of inflammatory and stabilizing CS/DS-GAG components in the ileum of patients with CD, and in preclinical models of CD. Such a finding would support future clinical trials testing EEN and CS/DS-GAGs in patients with CD.
Dr. Leticia Sewaybricker, PhD has been awarded a Pilot and Feasibility Award through the UW Nutrition Obesity Research Center for her project entitled: “Use of hypothalamic imaging in infants to understand postnatal weight gain.” Dr. Leticia Sewaybricker received her MD at the University of Campinas, Brazil, and subsequently completed both her residency and fellowship at the University of Campinas in Pediatrics. Dr. Sewaybricker then completed her PhD at the University of Campinas, Brazil in Child and Adolescent Health before completing her postdoctoral research fellowship at the University of Washington under the mentorship of Dr. Ellen Schur. Dr. Sewaybricker is currently an Acting Instructor of Medicine within the Division of General Internal Medicine at the University of Washington. She is a physician-scientist dedicated to studying prenatal influences on brain regulation of body weight and cardiometabolic function in children.
Project description: Early life exposures include both pre and postnatal factors that influence health throughout life. Among early life risk factors, rapid postnatal weight gain elevates the risk for obesity and other chronic diseases over the lifespan. Infants who experience fetal growth restriction more commonly present a rapid “catch-up” growth. The biological mechanisms involved in rapid postnatal weight gain are uncertain but could be through an effect of the prenatal environment on the hypothalamus. This work proposes to apply neuroimaging of the hypothalamus in infants to better understand the central nervous system contributors to postnatal weight gain. Previous studies have demonstrated that microstructural abnormalities (gliosis) in a key brain region for energy homeostasis, the mediobasal hypothalamus (MBH), precede obesity in animal models of diet-induced obesity, and is also associated with obesity in both children and adults. The aims of this proposal are to: 1) determine the role of neonatal hypothalamic gliosis in rapid postnatal weight gain; 2) using MRIs collected in infants with prenatal cannabis exposure (PCE) as a model of fetal growth restriction, determine if hypothalamic gliosis is increased in infants with PCE, and if this is associated with increased body weight gain. This work will advance our knowledge of central mechanisms that might link prenatal exposure to obesity risk and support future grant applications studying brain contributions to the early life origins of obesity.