Current Environment:


The cause(s) of Inflammatory Bowel Disease remain unknown and likely include a combination of genetic and environmental factors. Similarly, the ways in which IBD can affect a patient's health can vary considerably from person to person. The studies outlined here will gather valuable data that will help to identify patient populations that may be more or less likely to respond to a given medical or surgical therapy. In addition, we hope to identify which patients may be at higher risk for the development of particular complications of IBD or the medications used to treat these disorders.

Very Early Onset Inflammatory Bowel Disease Consortium

Roadmap to the Cure of Early Childhood IBD

Infantile and very early onset (VEO) inflammatory bowel disease is a severe and debilitating form of intestinal inflammation that has shown the most dramatic increase in incidence over the past decade and now makes up over 25% of all pediatric IBD. Infantile and VEO-IBD patients often suffer from a severe disease that does not respond to traditional therapies or surgery and unfortunately sometimes results in death. In order to understand and treat these young children we have established an international consortium made up of clinicians and scientists from North America, Europe, Australia, South America, Israel and the Middle East.

Our singular mission is the ambitious goal of both understanding the basis for these diseases as well to develop effective therapies.

The Roadmap to the Cure of Early Childhood IBD project is led by co-PIs Scott Snapper, Aleixo Muise from Canada, and Christoph Klein from Germany (please see attached bios). All co-PIs have been committed to fully understanding the genetic and functional aspects of this form of IBD and their recent work has led to discovery of novel genes resulting in alternate therapies for defined subgroups of infantile and VEO-IBD. The collaboration brings together the InterNational Early Onset Pediatric IBD Cohort Study (NEOPICS) in North America and the Care for Rare Study in Europe. Furthermore, sites in Israel, Australia, Brazil, Chile, and the Middle East have joined our collaborative study.

With generous donor and Helmsley Charitable Trust support, Dr. Snapper assembled an extraordinary group of international physicians and scientists in January 2013 as a working group charged with defining a roadmap to the cure of early childhood IBD. Principal Investigator (PI) Dr. Snapper and co-PIs from Canada (Aleixo Muise, MD, PhD) and Germany (Christoph Klein, MD, PhD) were joined by an interdisciplinary core group of 10 scientists—five from North America and five from Europe and Israel. All are leaders in their fields, encompassing basic science, disease research, diagnosis, and treatment related to the genetic, immunological, environmental, and therapeutic strategies that touch on early onset IBD. During their January meeting, participants zeroed in on the prime scientific questions that need to be answered and described the challenges, strategies, and resources needed to accelerate the quest for a cure. This work culminated in August 2013 in the development of a research roadmap to current

The group is launching studies to:

  • Create an innovative Pediatric VEO-IBD Portal for Personalized Patient Care (P4Care) Core to develop personalized treatments for VEO-IBD patients based on our understanding of the critical pathways associated with the disease.
  • Identify the genetic variants responsible for VEO-IBD and define the molecular networks which are dysregulated as a result of these variants.
  • Determine which environmental factors affect genetic and immunologic pathways relevant in VEO-IBD.
  • Develop a therapeutic pipeline to determine potential therapeutic targets within the currently identified pathways in VEO-IBD.

Together these consortia already have access to DNA from over 550 very early onset IBD patients many with stool, RNA, and biopsy samples. The inclusion of more US and European pediatric centers to the NEOPICS consortium will greatly increase the number of patient in a very short timeframe. This valuable resource will allow for rapid discovery of genetic determinants of infantile and VEO-IBD.

Currently patients are being recruited throughout the world.

For information please email Sophia Tollefson.

Microbial Factors in the Pathogenesis of Inflammatory Bowel Disease (CHIMP)

CHIMP is the Children’s Hospital Interdisciplinary Microbiome Project. The microbiome refers to all of the bacteria that live in the intestines. We believe these bacteria may provoke the immune system and play a role in making children with inflammatory bowel disease. To look at the bacteria in the gut, we collect stool samples from children with IBD while they are well and while they are sick. We also collect stool samples from children without IBD. Our first publication found marked differences between the microbiome of children with IBD and healthy children.

This important work is done with support from and in collaboration with the Crohn's and Colitis Foundation of America and the Leona M. and Harry B. Helmsley Charitable Trust.

In the future, we hope to develop a test that will help us tell whether someone has IBD just by looking at the types of bacteria in the stool. In addition to the microbiome, genetics likely play a role in the development of IBD. To look at genetics, we collect a small blood sample from children with IBD. This work will give us more clues as to the underlying causes of IBD and will help us develop better treatments.

For information, please contact Julia Bender Stern at

GEM Project (A Multidisciplinary Human Study on the Genetic, Environmental and Microbial Interactions that Cause IBD)

The greatest identifiable risk for development of Crohn's disease is having a first-degree family member affected by Inflammatory Bowel Disease (IBD). The cause of IBD is unknown but speculated to involve complex gene-environment interactions where susceptible individuals mount abnormal host responses to environmental factors such as resident gut microorganisms. The GEM Project will attempt to determine if specific gene-environment triggers can be identified. For this prospective study, unaffected siblings of Crohn's disease patients will be recruited and information on environmental exposures will be collected prospectively while simultaneously obtaining and storing biological samples on all subjects with the cohort. These subjects will be followed for up to 6 years. When a "sufficient" number of subjects have developed Crohn's disease, a nested case-control sampling of this cohort will allow for a focused examination of the changes in the microbial flora, intestinal permeability, immune response to bacterial antigen (Ag) and immune regulation, in relation to expressed IBD susceptibility genes. This will allow us to determine which pathogenic events may have contributed to disease prior to disease development.

For information, please contact Spencer Evans.

Pediatric Gastrointestinal Disease Biospecimen Repository and Registry

The Harvard IBD Longitudinal Data Repository is a tool to collect medical histories from every patient with inflammatory bowel disease at Boston Children's Hospital to track patient outcomes while easily identifying those who may be eligible for research studies more efficiently.

The registry was created to capture this information in a de-identified manner and will work in coordination with the Pediatric IBD Biospecimen Repository in order to help investigators here at Boston Children's Hospital and beyond answer important questions about the causes and pathogenesis of these diseases, evaluate innovative treatments, and further understand the genetic and environmental components that contribute to the development and course of IBD in the pediatric population.

For information, please contact Sophia Tollefson.

Pediatric Inflammatory Bowel Disease Biospecimen Repository

With the cause of inflammatory bowel disease (IBD) still largely unknown, this biospecimen repository will create a resource for investigators to test research hypotheses in the areas of disease pathogenesis, diagnostics, and prognosis.

Our repository will collect samples from patients with Crohn’s disease (CD) and ulcerative colitis (UC) as well as patients with debilitating, immune-mediated chronic bowel inflammation, including indeterminate colitis (IC) and primary immunodeficiencies that manifest with chronic bowel inflammation (eg. common variable immune deficiency, Wiskott-Aldrich syndrome). The repository will also be collecting samples from these patients' parents and siblings to help us learn more about how genetics and the environment play into the course of inflammatory bowel disease in children.

The development of an institutional IBD data registry will enhance the value of the biospecimen repository as all samples will be analyzed and linked to important clinical information, such as past and present treatments, diagnosis age, and family history. This will allow for easy integration of clinical and biological data to help us learn more about what causes IBD.

For information, please contact Sophia Tollefson.

Evaluation of Fecal and Serum ASCA Levels as Diagnostic Parameters Assessing Patients Suspected of Having Inflammatory Bowel Disease

ASCA are antibodies to a particular yeast (Saccharomyces Cervisae) that can be found in the blood of patients with Crohn's disease. The purpose of this research is to study and compare the levels of Anti-Saccharomyces cerevisiae antibodies (ASCA) in both the blood and stool of pediatric patients diagnosed with Inflammatory Bowel Disease (IBD). ASCA levels will be compared with disease severity, disease duration, and immunoglobulin levels. The goal of this study is to discover new ways to help physicians diagnose and treat their patients with inflammatory bowel disease without relying on invasive testing.

For information, please contact Kellen Mandehr at

Evaluation of Infliximab and HACA Levels

This study looks at how Infliximab levels and HACA antibody levels affect both remission rates and loss of response in patients with inflammatory bowel disease who have ever received this treatment.

For information, please contact Dr. Naamah Zitomersky at 617-730-4841.

The Impact of Inflammation on Brain White and Gray Matter, Structure, and Function in Pediatric Crohn's Disease

Steroids are very important anti-inflammatory drugs used in the treatment of IBD. When given in high doses, however, they may cause problems with thinking, behavior, and sleep. All of these may affect a student's learning and school performance. This study investigates if children and adolescents who are treated with steroids have more difficulties with learning, memory, and behavior/mood than children who are currently not on steroids. With this information we hope to find better ways to help families manage the drug side-effects in daily activities at home and in school. Eligible patients between the ages 8-17 years will receive a one-time neuropsychological assessment to determine attention, memory, learning, and cognitive ability. Summary of findings and recommendations will be provided to the family that can be helpful in planning medical and educational interventions if needed.

For information, please contact Christine Mrakotsky, PhD, Pediatric Neuropsychologist, at 617-355-7490.