The Gastroenterology, Hepatology and Nutrition Division is devoted to shaping the way we understand and care for children with digestive and hepatobiliary diseases through cutting edge clinical and laboratory research. Our research programs are supported by major funding organizations such as the National Institute of Health, Children's Digestive Health and Nutrition Foundation, and the Crohn's and Colitis Foundation of America.
Our Division works closely with the Digestive Disease Research Center (DDRC) on multiple projects. The DDRC promotes digestive diseases-related research in an integrative, collaborative and multidisciplinary manner. In addition to enhancing the basic research capabilities of established investigators, the center attracts investigators not currently involved in digestive diseases-related research to pursue these lines of investigation in order to facilitate the translation of basic research findings to the clinical area. The center also develops and implements programs for training and establishment of young investigators in digestive diseases-related research.
Read more about our investigators and their research improving the lives of children with intestinal and liver disease.
Dr. Acra's major clinical and research focus areas are in nutrition and upper gastrointestinal pathology, including eosinophilic esophagitis and esophageal disorders. As the Director of a Pediatric Aero-digestive program, Dr. Acra conducts studies on dyspeptic disorders including piloting a novel non-invasive technology for measuring esophageal inflammation via measurement of mucosal electric resistance.
In early publications, Dr. Acra described the physiology of electrolytes transportation in both animal and human models. This work represented a significant step in the understanding of activity in various intestinal transporters, including the Na -H and CI-HCO3- exchangers in both health and disease. His work also contributed to the initial description of a distinct Na -H exchanger in human intestinal epithelia.
Recent research efforts have shifted focus to the investigation of physiological regulation of energy metabolism in both healthy children and in those with inflammatory bowel disease and other chronic disease states. This has expanded to include efforts to improve the technologies for measuring body composition and physical activity. With the results of cohort studies by a multi-disciplinary team funded through NIH grants and involving more than 150 pediatric subjects and advanced modeling, have led to the ability to accurately and objectively measure free-living energy expenditure of physical activity in children. The multidisciplinary team involved in these studies is currently using these techniques to understand the implications of clinical disease on physical activity and fatigue in children with IBD.
Dr. Acra is part of a multidisciplinary program continuously supported for over 25 years through NIH funding that investigates bio-psychosocial processes associated with pediatric functional abdominal pain conditions including Irritable Bowel Syndrome and Functional Dyspepsia. The team recently completed a prospective study of more than 700 pediatric patients with functional abdominal pain followed from childhood into adolescence and young adulthood. The results of these studies have led to predicators of persistence of functional pain from childhood into adulthood, allowing earlier targeted care for those with greatest predilection for chronicity.
As a Professor in Pediatrics and Chief of the D. Brent Polk Division of Pediatric Gastroenterology, Dr. Acra has mentored several junior faculty and Pediatric GI fellows, of whom over two-thirds remain in academics, and five of whom have received young investigator awards from national specialty societies. Dr. Acra currently serves as a co-PI and Associate Director of an NIH T32 training grant in gastroenterology held jointly with Adult GI.
Dr. Hiremath is a board certified pediatric gastroenterologist with a broad background in epidemiology, biostatistics, research methods, and biomedical imaging. He leads the pediatric eosinophilic gastrointestinal disorders clinic at Vanderbilt. This multi-disciplinary clinic focuses on providing exceptional clinical care to individuals with eosinophilic gastrointestinal diseases and also allows him to conduct patient-oriented innovative and original research.
Through his research, Dr. Hiremath aims to positively impact care and promote clinical outcomes among individuals affected by eosinophilic gastrointestinal diseases. At Vanderbilt, he has developed a multipronged interdisciplinary approach to address some of the outstanding questions in the field of eosinophilic esophagitis. Specifically, his research program focuses on the epidemiology, pathogenesis and diagnosis of this onerous condition. Using his prior training and experiences he is delving into the epidemiology of eosinophilic esophagitis and eosinophilic gastrointestinal diseases. Through his secondary appointment in the Vanderbilt School of Biomedical Engineering he is applying advanced biomedical technologies to gain novel insights into the pathogenesis and molecular mechanisms underlying the development and progression of eosinophilic esophagitis. He is working with his collaborators within the Vanderbilt University and with experts all across the nation to conceptualize and develop non-invasive and/or minimally invasive approaches to diagnose and/or monitor eosinophilic esophagitis.
Dr. Hiremath has been conducting eosinophilic gastrointestinal diseases research for more than a decade. His commitment to patient care and eosinophilic esophagitis research has been recognized at institutional level through the Turner-Hazinski Junior Faculty Career Development award and the Katherine Dodd Faculty Scholar award. His single minded devotion to the field has been recognized by his peers through his nomination to the Society for Pediatric Research. His research has earned him several accolades including an appointment to the National Institutes of Health training grant, the Consortium of Eosinophilic Gastrointestinal Disease Researchers training award, American College of Gastroenterology Junior Faculty Career Development award.
Dr. Nicholson has a broad background in clinical and epidemiologic pediatric research including advanced training in biostatistics and protocol development as well as experience conducting prospective studies requiring patient enrollment. She has previously conducted both retrospective and prospective studies evaluating pediatric Clostridium difficile infections which were completed through a highly competitive T32 training grant and the Thrasher Early Career Award.
Her early publications directly addressed the issues concerning variable outcomes in pediatric C. difficile disease under the mentorship of Dr. Kathryn Edwards. Through a comprehensive retrospective analysis, they were able to detail risk factors for recurrent disease. Then they prospectively enrolled patients with a C. difficile infection and studies stool inflammatory markers their association with disease recurrence in collaboration with Dr. Herbert DuPont of the University of Texas. These archival samples were then available for further study, where Dr. Nicholson was able to demonstrate an association between stool inflammatory markers and C. difficile disease severity in children through collaboration with the laboratory of Eric Skaar at Vanderbilt. These findings were published in Nature Medicine. Dr. Nicholson has also published review articles in this field to highlight the difficulties associated with C. difficile diagnostics in young children and pediatric transplant recipients. Through her work, she has effectively elucidated the emerging difficulties surrounding C. difficile testing and outcome determination.
Dr. Nicholson's early work inspired her interest in outcomes associated with other infectious diarrheal illnesses. Particularly, she has focused her current work on the role of co-infections that involve C. difficile and an additional pathogen. Through her research evaluating the gastrointestinal pathogen detections in 2016 stool samples in pediatric patients with acute gastroenteritis, she identified 72 percent of those with C. difficile detection were also positive for an additional infectious agent on multiplex molecular testing. However, these patients were without a clinical difference, concerning for the possibility that C. difficile was colonizing the host and not the cause of the symptoms. Dr. Nicholson's current work aims to focus on additional means to characterize C. difficile colonization in the pediatric host.
During the last four years as an Assistant Professor of Pediatrics in Pediatric Gastroenterology, Hepatology, and Nutrition, Dr. Nicholson has established a monthly Pediatric C. difficile Clinic which cares for children with refractory and recurrent C. difficile disease. She has also established the Pediatric Fecal Microbiota Transplantation (FMT) program at Monroe Carell Jr. Children's Hospital at Vanderbilt and established herself as an expert in the treatment of C. difficile infections at Vanderbilt and nationally as the co-PI on a multi-center consortium evaluating fecal microbial transplant (FMT) in pediatric patients with recurrent C. difficile She was awarded the NASPGHAN Young Faculty Clinical Investigator Award for this week. She is also co-chair of the NASPGHAN FMT Specific Interest Group. Additionally, Dr. Nicholson has worked with the NIH-funded Vanderbilt Vaccine Treatment and Evaluation Unit (VTEU) for protocol development of an upcoming FMT study by retention enema. In 2017, she received a KL2 award and now spends over 75 percent of her time studying C. difficile infections in the pediatric population and is an active member of the Skaar Research Laboratory. She is currently enrolling pediatric patients with a diagnosis of C. difficile infection as well as those patients with concern for colonization (patients with cystic fibrosis, cancer, inflammatory bowel disease) to evaluate for toxin and microbiome predictors of variable disease states. As part of a separate study, she is also enrolling pediatric patients with active C. difficile infection to receive Bezlotoxumab, an FDA-approved [in adults] therapeutic agent, to prevent further episodes of recurrence.
As an Assistant Professor of Pediatric Gastroenterology and a graduate of an Integrative Medicine Fellowship at the University of Arizona, Dr. Russell bridges these two disciplines with a research interest in the evaluation and treatment of pediatric functional GI disorders, particularly chronic nausea. In collaboration with Dr. Lynn Walker's laboratory, she has been conducting research describing the short and long-term morbidity of chronic nausea on adolescents with functional abdomial pain. This research was selected for a platform presentation at Digestive Disease Week, May 2015.
In 2016, Dr. Russell established the first Pediatric Nausea Clinic to specialize in chronic nausea. As a clinical program within the Pediatric GI program for the evaluation and treatment of chronic nausea in children, she is working to advance the understanding of this condition through cutting edge research supported by the National Institute of Health. Amongst its research aims, the program has begun to follow a cohort of patients for the longitudinal assessment of the determinants and outcomes of nausea, including detailed psychological and physiologic phenotyping.
Dr. Russell is additionally part of a multidisciplinary research team funded by the NIH to develop noninvasive markers of disease severity in children with chronic nausea. This team has received R01 funding to design, test, and implement a novel noninvasive bioelectric measurement and analysis procedure called an electrogastrogram, specifically for children with chronic nausea.
Dr. Yan's research is focused on the signaling mechanisms underlying the pathogenesis of inflammatory bowel diseases and the symbiotic relationship between gut microbiota and the host in maintaining intestinal homeostasis. Her lab's research efforts have led to over 46 peer-reviewed publications, 10 review articles, and 4 U.S .and European patents. Dr. Yan has also been invited to present her research at the Basic Plenary Session during Digestive Disease Week in 2008 and again, in 2017.
Dr. Yan has demonstrated expertise in elucidating the mechanisms of signaling pathways induced by activation of TNF receptor and EGF receptor in intestinal epithelial cells and in macrophages in regulating intestinal homeostasis. This research experience has enabled Dr. Yan to initiate investigations into the molecular mechanisms of probiotic action. Her lab has successfully used Lactobacillus rhamnosus GG (LGG) as a probiotic bacterial model to study the mechanisms of the symbolic host-microbial relationship in regulation of gastrointestinal growth and disease. They have isolated and cloned an unique LGG-derived soluble protein, p40 (named by Dr. Yan). She has demonstrated how p40 enhances intestinal epithelial cell homeostasis through activation of EGF receptors, thereby, preventing and treating intestinal inflammation. p40 is the first probiotic-derived factor found to contribute to the beneficial effects of probiotics in the host. This discovery has been a significant advance in the field of probiotic research.
Future research goals include expanding efforts to understand the effects and mechanisms of intestinal epithelial cells on the regulation of microbiota under physiological conditions in order to reveal the impact of intestinal inflammation in this symbiotic relationship. Dr. Yan’s novel hypothesis reasons the beneficial effects of LGG toward maintaining intestinal homeostasis are facilitated by intestinal epithelial cell-derived heat shock protein 90 in extracellular vesicles. This regulatory effect by epithelial cells can disrupted by intestinal inflammation.
Our outstanding clinical fellows spend two years of their training dedicated to research and post-doctoral education. Current and past fellows have conducted basic and clinical scholarly work in inflammatory bowel disease, liver disease, obesity, functional abdominal disorders, gastroesophageal reflux disease, H. pylori, and global health.
Last Edited: August 13, 2018