2011 Research Annual Report

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Gastroenterology, Hepatology and Nutrition

 

Division Data Summary

Research and Training Details

Number of Faculty30
Number of Research Fellows3
Number of Research Students1
Number of Support Personnel69
Direct Annual Grant Support$5,093,117
Direct Annual Industry Support$101,184
Peer Reviewed Publications89

Clinical Activities and Training

Number of Clinical Staff47
Number of Clinical Fellows13
Inpatient Encounters8714
Outpatient Encounters15158

Division Photo

Gastroenterology, Hepatology and Nutrition Division.

Row 1: X Han, J Heubi, M Cohen, W Balistreri, J Bezerra

Row 2: S Saeed, J Franciosi, L Denson, C Wetzel, S Xanthakos

Row 3: A Miethke, J Palermo, M Farrell, P Putnam, R Kohli, S Moore

Significant Publications

Moyer K, Kaimal V, Pacheco C, Mourya R, Xu H, Shivakumar P, Chakraborty R, Rao M, Magee J, Bove K, Aronow BJ, Jegga AG, Bezerra JA. Molecular subtypes of biliary atresia with relevance to clinical outcome. Genome Med. 2:33. 2010.

Matte U, Miethke A, Liu C, Mourya R, Kauffmann G, Moyer K, Zhang K, Wang N, Bull L, Thompson R, Spinner NB, Bezerra JA. High-throughput sequence analysis of multiple genes in patients with inherited syndromes of intrahepatic bile ducts. J Ped Gastroenterol Nutr. 51:488-93. 2010.

Biliary atresia and inherited cholestatic syndromes comprise the most common causes of chronic liver diseases in neonates and children. In two publications, Dr. Bezerra and co-investigators validated a molecular chip to screen for mutations that cause cholestasis in children. Using this chip, they were able to diagnose specific syndromes in a substantial number of children with chronic liver disease in whom no specific cause could be established. Further, analyzing livers of children with biliary atresia, they discovered a molecular signature that enables the staging of disease at the time of diagnosis. These findings will facilitate the diagnostic algorithms in clinical practice and improve clinical trials to take into account the biological makeup of children with liver disease.
Moore SR, NL Lima, Soares AM, Oriá RB, Pinkerton RC, Barrett LJ, Guerrant RL, Lima AA. Prolonged episodes of acute diarrhea reduce growth and increase risk of persistent diarrhea in children. Gastroenterology. 39: 1156-64. 2010.
We conducted a decade-long prospective cohort study of diarrhea among children (n=414) born into a poor periurban community in Brazil's tropical, developing Northeast region in order to elucidate the epidemiology and impact of prolonged episodes of acute diarrhea (ProD, duration >7 and <13 days) in a highly endemic setting. Our key findings include: 1) 50% of all days with diarrhea were attributable to ProD or persistent diarrheal (PD, >14 days) episodes, 2) ProD was associated with Shigella and Cryptosporidium infections, 3) a reciprocal relationship between ProD and undernutrition, and 4) a robust correlation of infantile ProD with future risk for PD. Taken together, these finding suggest that ProD accounts for significant morbidity and identifies children at risk of a vicious cycle of diarrhea and malnutrition.
Crandall W, Kappelman M, Colletti R, Leibowitz I, Grunow J, Ali S, Baron H, Berman J, Boyle B, Cohen S, del Rosario F, Denson L, Duffy L, Integlia M, Kim S, Milov D, Patel A, Schoen B, Walkiewicz D, Margolis P. ImproveCareNow: The Development of a Pediatric IBD Improvement Network. Inflamm Bowel Dis. 17:450-7. 2011.
Variation in care seems to be the norm rather than exception in care of chronic medical conditions. This is true for pediatric inflammatory bowel disease as well. It has been demonstrated that development of evidence based treatment guidelines and quality improvement science methods can help address unwarranted variation in care and outcomes. Here we report the establishment of The ImproveCareNow Network as a prototype for a model of improving subspecialty care that includes three components: 1) creating enduring multicenter collaborative networks of pediatric subspecialists, 2) sharing of performance data collected in patient registries, and 3) training in quality improvement. The network began with a focus on improving initial diagnostic testing and evaluation, the classification of the severity and extent of disease, the detection and treatment of inadequate nutrition and growth, and the appropriate dosing of immunomodulator medications. Changes are based on an evidence-based model of chronic illness care involving the use of patient registries for population management, previsit planning, decision support, promoting self-management, and auditing of care processes. Currently, patients are being enrolled at 31 sites. In the paper, we report analyzed data on over 2500 patients from over 7500 visits. Initial results suggest improvements in both care processes (e.g., appropriate medication dosing and completion of a classification bundle that includes the patient's diagnosis, disease activity, distribution and phenotype, growth status, and nutrition status) and outcomes (e.g., the percentage of patients in remission).
Kohli R, Kirby M, Setchell KDR, Jha P, Klustaitis K, Woollett LA, Pfluger PT, Balistreri WF, Tso P, Jandacek RJ, Woods SC, Heubi JE, Tschoep MH, D’Alessio DA, Shroyer NF, Seeley RJ. Intestinal adaptation after ileal interposition surgery increases bile acid recycling and protects against obesity related co-morbidities. Am J Physio.299: G652 - G660. Sep, 2010.
Surgical interventions for obesity (Bariatric Surgery) have become an established treatment for both adults and adolescents who are morbidly obese. The interposition of distal ileum into the proximal jejunum is a bariatric procedure that improves the metabolic syndrome. Changes in intestinal and hepatic physiology after ileal interposition (transposition) surgery (IIS) are not well understood. Our aim was to elucidate the adaptation of the interposed ileum, which we hypothesized, would lead to early bile acid reabsorption in the interposed ileum, thus short circuiting enterohepatic bile acid recycling to more proximal bowel segments. Rats with diet-induced obesity were randomized to IIS, with 10 cm of ileum repositioned distal to the duodenum, or sham surgery. A subgroup of sham rats was pair-fed to IIS rats. Physiological parameters were measured until 6 wk postsurgery. IIS rats ate less and lost more weight for the first 2 wk postsurgery. At study completion, body weights were not different, but IIS rats had reversed components of the metabolic syndrome. The interposed ileal segment adapted to a more jejunum-like villi length, mucosal surface area, and GATA4/ILBP mRNA. The interposed segment retained capacity for bile acid reabsorption and anorectic hormone secretion with the presence of ASBT and glucagon-like-peptide-1-positive cells in the villi. IIS rats had reduced primary bile acid levels in the proximal intestinal tract and higher primary bile acid levels in the serum, suggesting an early and efficient reabsorption of primary bile acids. IIS rats also had increased taurine and glycine-conjugated serum bile acids and reduced fecal bile acid loss. There was decreased hepatic Cyp27A1 mRNA with no changes in hepatic FXR, SHP, or NTCP expression. IIS protects against the metabolic syndrome through short-circuiting enterohepatic bile acid recycling. There is early reabsorption of primary bile acids despite selective "jejunization" of the interposed ileal segment. Changes in serum bile acids or bile acid enterohepatic recycling may mediate the metabolic benefits seen after bariatric surgery.
Steinbrecher KA, Harmel-Laws E, Garin-Laflam MP, Mann EA, Bezerra LD, Hogan SP, Cohen MB. Murine Guanylate Cyclase C Regulates Colonic Injury and Inflammation. J Immunol. 186(12):7205-14. 2011.
Guanylate cyclase C  and its ligands, guanylin and uroguanylin, are expressed in intestinal epithelial cells (IECs) and regulate ion secretion, intestinal barrier function, and epithelial monolayer homeostasis via cGMP-dependent signaling pathways.  Recent studies indicate that GC-C and its ligands direct the course of intestinal inflammation.  We found that chemically-induced clinical disease and histological damage to the colonic mucosa were significantly less severe in GC-C knockout mice.  Basal and inflammation-induced production of resistin-like molecule β (RELMβ) was substantially diminished in GC-C knockout mice.  RELMβ is thought to stimulate cytokine production in macrophages in this disease model and, consistent with this, TNFα and IFNγ production was minimal in mice lacking GC-C.  Colonic instillation of recombinant RELMβ by enema into these animals restores sensitivity to DSS-mediated mucosal injury.  These findings demonstrate a novel role for GC-C signaling in facilitating mucosal wounding and inflammation and further suggest that this may be mediated, in part, through control of RELMβ production.

Division Highlights

Kathleen Campbell, MD; John Bucuvalas, MD; Jorge Bezerra, MD; Mike Leonis, MD, PhD

Pediatric Liver Transplant Program

The Pediatric Liver Transplant Program continues its’ mission of advancing the care of liver transplant recipients by improving the health care delivery system, providing unparalleled clinical care, and addressing gaps in knowledge through patient-based and basic laboratory research. The program remains one of the largest pediatric liver transplant programs in the country, with excellent clinical outcomes at or above the national average. Clinical highlights in fiscal year 2011 included the incorporation of advanced practice nurses into the inpatient care delivery team, a successful site survey from the United Network for Organ Sharing (the primary regulatory agency for solid organ transplantation in the United States), and a growing niche area in transplantation for hepatic tumors, fostered in collaboration with the Oncology division.  In Fall 2010 the Liver Transplant program was chosen, in combination with the Biliary Atresia Program, as one of the first “High Impact Conditions” defined by hospital leadership as a focus area for achievement of “Best In Class” status by 2015, highlighting the strong accomplishments and solid performance of the program over time. Members of the Liver Transplant Program continue to be leaders in national quality improvement efforts and multi-center clinical and translational studies.  These include: the Pediatric Acute Liver Failure Study Group (PALF), Medication adherence in children who had a liver transplant (MALT), Functional outcomes in liver transplant recipients (FOG), Immunosuppression withdrawal for sable pediatric liver transplant recipients (iWITH), Studies in Pediatric Liver Transplantation (SPLIT) clinical registry, SPLIT Quality Improvement  Initiative sponsored by the CCHMC Center for Education and Research on Therapeutics, Calcineurin Inhibitor Minimization and Foxp3+ T-regs post-transplant.

Stavra Xanthakos, MD; Rohit Kohli, MD

Cincinnati Children's Steatohepatitis Center

The Cincinnati Steatohepatitis Center (CCSC) is a multidisciplinary clinic initiated in November 2007 to care for the unique needs of pediatric patients with nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). NAFLD, the hepatic consequence of obesity and metabolic syndrome, affects about 10% of children and ranges from fatty liver alone (NAFLD) to fatty liver with varying degrees of liver inflammation and fibrosis (NASH). NASH is estimated to progress to cirrhosis and liver failure in an estimated 25% of adult individuals; we have shown that fibrosis can progress even in childhood.

The CCSC evaluates patients for alternate causes of elevated liver enzymes and screens for closely related comorbidities including insulin resistance, hypertension, dyslipidemia, type 2 diabetes mellitus, polycystic ovarian syndrome and obstructive sleep apnea. For therapy, enrollment into intensive weight management programs such as Healthworks! is encouraged, but the clinic also provides individualized dietary consultation and recommendations for families who cannot participate in more intensive programs and follows progress in meeting nutritional and activity goals.

The CCSC faculty include: Stavra Xanthakos MD, MS (medical director), Rohit Kohli MBBS, MS (co-director) and William Balistreri, MD. Access has been increased this year by incorporating a nurse practitioner into our program as well. Research programs in the CCSC have also significantly expanded since its inception and aim to improve our understanding and treatment options for this disease. Researchers in the CCSC are currently studying the outcome of NASH after bariatric surgery in adolescents (K23DK080888, PI: Xanthakos) and animal models of bariatric surgery and NASH (K08 DK084310, PI: Kohli). The CCSC is a major participating pediatric site in the NIH-funded NASH Clinical Research Network (U01 DK08505, Center PI: Xanthakos), a multi-center study investigating the natural history and determinants of NASH in adults and children and will be offering a clinical therapeutic trial anticipated to begin in early 2012.

The CCSC has published clinical and pre-clinical papers in the area of steatohepatitis research over the last year in the following journals: Hepatology; Journal of Pediatric Gastroenterology and Nutrition, and the American Journal of Physiology, and Journal of Hepatology. The CCSC continues to give talks to local community pediatric care providers and practices. The CCSC presented its outcomes data at the annual meeting of the North American Society for Pediatric Gastroenterology at its annual meeting last year.

Phil Putnam, MD; James Franciosi, MD

Cincinnati Center for Eosinophilic Disorders (CCED)

The CCED is a high volume, multidisciplinary tertiary referral care center specializing in Eosinophilic Gastrointestinal Disorders (EGID) in both the pediatric and adult populations. The core clinical group is made up of members from the Divisions of Gastroenterology, Nutrition and Hepatology, Allergy and Immunology, Social Work and Nutrition. The CCED extensively utilizes a number of ancillary services within the hospital during the process of treating these patients. Families are seen for a week long baseline visit and then subsequent, one day follow visits on a regular basis (at least once yearly).

In 2010, the CCED physician’s and staff managed cared for 515 distinct patients that included:  190 new patient cases from 44 states (including Ohio) and one country outside of the U.S. (Peru), over 722 endoscopic procedures on patients with an EGID diagnosis (24% of the total GI endoscopies at CCHMC), and 607 GI clinic visits.

Research through the CCED involves basic, clinical and translational studies. Patients are offered enrollment in diverse research studies including epidemiology, quality of life research, descriptive research databanks, specimen databanks (collections of endoscopy tissue, blood, and DNA), translational studies, and clinical trials.  In 2010, members of the CCED team published over 15 papers on eosinophilic disorders in major medical journals including the journal Nature Genetics.  Dr. Franciosi has further characterized the epidemiology of eosinophilic esophagitis as a chronic, under-recognized inflammatory condition in children.  The CCED team has also determined that EGID conditions have a significant negative impact on quality of life.  Dr. Rothenberg’s laboratory has identified a gene possibly involved in susceptibility to eosinophilic esophagitis at the 5q22 locus. 

As a continuation of our $1.5 million NIH stimulus research grant awarded in 2009, the first national Registry for Eosinophilic Gastrointestinal Disorders (www.regid.org) has been launched in 2010 and will begin enrolling patients in 2011.  The CCED is leading a multi- center registry collaboration with eight pediatric and adult hospitals with plans for further expansion. 

Jorge Bezerra, MD; Mitchell Cohen, MD; Cynthia Wetzel, PhD

Digestive Health Center (DHC)

The DHC is one of 17 Silvio O. Conte Digestive Diseases Research Core Centers in the nation supported by the National Institutes of Diabetes & Digestive & Kidney Diseases. The DHC, located within the Division of Gastroenterology, Hepatology, and Nutrition at Cincinnati Children's Hospital Medical Center is the only Core Center dedicated to research on pediatric digestive diseases. The DHC cores provide services to increase the tempo of scientific discoveries in digestive disease research and to attract new investigators to the field.  The overall goal of the DHC, is to promote research that will yield insights into the fundamental processes and pathogenic mechanisms of digestive disease in children and generate innovative treatment to restore digestive health.  Specifically,  the long term goals are to improve child health through better diagnosis, treatments and outcomes for our 4 key focus areas and diseases: 1) Chronic Liver Disease (biliary atresia, chronic cholestasis, and liver transplantation); 2) Inflammatory and Diarrheal Diseases (inflammatory bowel disease, eosinophilic gastrointestinal disorders, and infectious diarrhea) 3) Obesity and the Digestive System (including liver and metabolic complications of obesity), and 4) Development and Digestive Diseases (molecular basis of organogenesis, adult stem cell/homeostasis, and intestinal organoids from stem cells). The focus areas are linked by four highly innovative Biomedical Research Cores: Gene and Protein Expression, Bioinformatics, and Integrative Morphology; a Biostatistical Service is also available through a collaborative effort with the Center for Clinical and Translational Science and Training Program). In addition, the DHC provides 3-6 pilot and feasibility awards each year to investigators starting research projects with the potential for extramural funding.  The DHC director is Dr. Jorge Bezerra, the associate Directors are Drs. Mitchell Cohen, Aaron Zorn, and Marshall (Chip) Montrose, and the Project Manager is Dr. Cynthia Wetzel. The DHC has 56 investigators and 29 associate members from 17 different divisions within the Department of Pediatrics and a total of 8 departments within the University of Cincinnati, College of Medicine.

Scott Pentiuk, MD

Interdisciplinary Feeding Team (IFT)

This multi-disciplinary team provides comprehensive evaluation of children with swallowing/feeding disorders. It includes members from gastroenterology, otolaryngology, human genetics, speech therapy, occupational therapy, social work, and nutrition. Dr. Scott Pentiuk MD is the pediatric gastroenterologist on the team. The IFT continues to grow at nearly 10% per year with over 1200 patient visits over the last year. The team has also expanded its outpatient treatment programs with the development of co-treatment sessions and Parent-Child Interaction Training for families. Current IFT research projects include the use and development of a pureed by G-tube diet, quality of life assessment of feeding therapies, methods to evaluate children with swallowing dysfunction, and the creation of a prospective database in order to track the effectiveness of therapies and patient outcomes.

Jorge Bezerra, MD; Alex Miethke, MD

Chronic Liver Disease Program

The Bezerra laboratory investigates regulatory mechanisms of liver and biliary injury. One major research focus is pre-clinical and translational research on biliary atresia, the most common cause of chronic liver disease in children. He has used large-scale expression arrays and bioinformatics to develop transcriptional maps for human and murine biliary atresia. These maps generated hypotheses regarding pathogenic mechanisms of disease. Testing these hypotheses in the laboratory, he began dissecting the cellular and molecular basis of neonatal injury and obstruction of extrahepatic bile ducts using unique in vitro and experimental models of disease. Experiments identified key regulatory functions for hepatic dendritic cells and CD8+ and NK lymphocytes in recognition and induction of apoptosis of the bile duct epithelium. Ongoing experiments are identifying co-stimulatory signals controlling cell survival during early postnatal development and small molecules regulating biliary diseases. In translational studies, he is also applying state-of-the-art approaches to identify the molecular determinants of treatment response in multi-center studies of children with biliary atresia and syndromes of intrahepatic cholestasis.

Division Collaboration

Biomedical Informatics » Bruce Aronow, PhD; Anil Jegga, DVM, MRes

Collaboration through the Digestive Health Center: Bench to Bedside Research in Pediatric Digestive Disease - Jorge Bezerra, MD

Studies of the molecular basis of clinical phenotypes of biliary atresia - Jorge Bezerra, MD

Developmental Biology » S Steven Potter, MD; Aaron Zorn, PhD; James Wells, PhD

Collaboration through the Digestive Health Center: Bench to Bedside Research in Pediatric Digestive Disease - Jorge A. Bezerra, MD

Studies of development and function of the biliary system - Jorge Bezerra, MD 

Pathology » David P Witte, MD; Keith F Stringer, MD; Rachel Sheridan, MD; Kevin Bove, MD

Collaboration through the Digestive Health Center: Bench to Bedside Research in Pediatric Digestive Disease - Jorge Bezerra, MD

Studies of mechanisms of hepatic tumorigenesis - Jorge Bezerra, MD

Molecular staging of liver injury in biliary atresia - Jorge Bezerra, MD

Molecular Immunology » Claire Chougnet, PhD; Kasper Hoebe, PhD

Studies of the role of the immune system in pathogenesis of biliary atresia - Jorge Bezerra, MD

Studies of mechanisms of hepatic tumorigenesis - Jorge Bezerra, MD

Animal models of liver diseases - Jorge Bezerra, MD

Immunobiology » Marsha Wills-Karp, PhD; Jochen Mattner, MD, PhD

Collaboration through the Digestive Health Center: Bench to Bedside Research in Pediatric Digestive Disease - Jorge Bezerra, MD

Studies of mechanisms of auto-immune liver disease - Jorge Bezerra, MD

Pediatric Surgery; Liver Care Center » Greg Tiao, MD; Jaimie Nathan, MD

Studies of the virologic basis of biliary atresia - Jorge Bezerra, MD

Studies of immunologic injury of bile ducts - Jorge Bezerra, MD

Allergy & Immunology » Simon Hogan, PhD

Effects of weanling undernutrition and glutamine dipeptide supplementation on intestinal barrier function in mice - Sean Moore, MD

Paired Immunoglobulin Receptor B Regulation of Innate Intestinal Immunity - Kris  Steinbrecher, PhD

Pathogenic role of the macrophage in ulcerative colitis - Kris Steinbercher, PhD

Role of Signal Transducer and Activator of Transcription 5 in Gut Injury - Xiaonan Han, PhD

Global Health Center; Infectious Diseases » Mark Steinhoff, MD; Elizabeth Schlaudecker, MD
Interactions of diarrhea, pneumonia, and malnutrition in childhood - Sean Moore, MD
James M Anderson Center for Health System Excellence » Peter Margolis, MD, PhD; Michael Seid, PhD
Collaborative Chronic Network (C3N) / Enhanced Registry grant - develop a network of collaborators (physicians, patients, researchers) that transforms the outcomes and experience of patients with IBD, accelerate discovery and application of new knowledge by employing Quality Improvement tools, and information technology - Shehzad Saeed, MD
Psychology » Kevin Hommel, PhD
Adherence in Pediatric IBD - Examine the effects of telehealth behavioral treatment (TBT) on medication adherence in children with IBD, disease severity, quality of life and health care utilization versus education only (EO) intervention - Shehzad Saeed, MD
Adolescent Medicine » Ellen Lipstein, MD, MPH
Assessment of decision making in choosing biological therapy for treatment of Crohn's disease employing qualitative interviewing tools - Shehzad Saeed, MD
Adherence Center » Sandra Corina, PhD
Developing culturally sensitive behavioral therapies for patients of middle eastern origin admitted to CCHMC - Shehzad Saeed, MD
Pulmonary Medicine » John P Clancy, MD
Centralized Intestinal Current Measurement testing, and comparison of suction and forceps-based biopsy performance - Shehzad Saeed, MD
Otolaryngology; Human Genetics; Speech Therapy; Occupational Therapy; Social Services » Interdisciplinary Feeding Team
Multi-disciplinary team provides comprehensive evaluation of children with swallowing/feeding disorders - Scott Pentiuk, MD
Hematology/Oncology » Joseph Palumbo, MD
Hemostatic Factors in Colitis and Colitis-Associated Colon Cancer - Kris  Steinbrecher, PhD
Pathology » Kenneth Setchell, PhD; Lili Miles, MD; Peter Tang, PhD; Michael Miles, PharmD

Bile acids in animal models of bariatric surgery - Rohit Kohli, MD

Hepatic histology in NASH animal models - Rohit Kohli, MD

Coenzyme Q as a biomarker for NASH - Rohit Kohli, MD

Allergy » Senad Divanovic, PhD
The role of IL-17 in NASH - Rohit Kohli, MD
Infectious Diseases » Monica McNeal, MS; David Bernstein, MD
Effect of weanling malnutrition on the immunogenicity of oral rotavirus vaccines - Sean Moore, MD
Pathology » Kevin Bove, MD
Histomorphology of inherited cholestatic liver diseases - Alexander Miethke, MD
Molecular Immunology » Claire Chougnet, PhD
The role of regulatory T cells in biliary atresia - Alexander Miethke, MD
Neonatology; Pediatric Surgery » Andrew South, MD; Michael Helmrath, MD
Clinical and translational research characterizing children with and at risk for intestinal failure - Conrad Cole, MD; Samuel Kocoshis, MD; Adam Mezoff, MD; Noah  Shroyer, PhD
Pediatric Surgery; Neonatology; Biostatistics & Epidemiology » Michael Helmrath, MD; Andrew South, MD; Eileen King, PhD
Efficacy of enteral glutamine in pediatric SBS - Conrad Cole, MD; Samuel Kocoshis, MD; Adam Mezoff, MD
Surgical Weight Loss Program for Teens; Center for Bariatric Research & Innovation » Thomas H Inge, MD, PhD; Todd Jenkins, PhD

Biological Determinants of Steatohepatitis - Stavra Xanthakos, MD

Teen LABS U01 - Stavra Xanthakos, MD

Surgical Weight Loss Program for Teens - Stavra Xanthakos, MD

Endocrinology » Nancy Crimmins, MD
NAFLD in Youth with Type 2 diabetes: An Important but Under-Recognized Co-Morbidity - Stavra Xanthakos, MD
General & Community Pediatrics; Cardiology; Endocrinology » Robert Siegel, MD; Holly Ippisch, MD; Nancy Crimmins, MD
Advanced Metabolic Clinic, a monthly multidisciplinary clinic for children with multiple obesity-related complications - Stavra Xanthakos, MD
Nephrology & Hypertension » Jens Goebel, MD
Calcineurin Inhibitor Minimization and Foxp3+ Tregs Post-Transplant - John Bucuvalas, MD
Center for Adherence and Self-Management » Dennis Drotar, PhD
Clinical Center for Medical Adherence in Liver Transplant Recipients: Etiopathogenesis and clinical outcome - John Bucuvalas, MD
Immunology » Lisa Filipovich, MD
Acute Liver Failure in Children: Role of immune dysregulation - John Bucuvalas, MD
Center for Health Care Quality; Pulmonary Medicine » Peter Margolis, MD, PhD; Michael Seid, PhD
"Transforming Chronic Illness Care" - The specific aim is to design, prototype, optimize, and evaluate a patient-provider C3N to improve clinical practice, patient self-management, and disease outcomes of pediatric inflammatory bowel disease (IBD) - John Bucuvalas, MD
Allergy & Immunology; ; Behavioral Health » Marc Rothenberg, MD, PhD; J Pablo Abonia, MD, PhD; Kevin Hommel, PhD
Quality of Life and Symptom Severity Outcome Measures in Eosinophilic Esophagitis: Beyond Eosinophil Counting - James Franciosi, MD
Allergy & Immunology; ; Biomedical Informatics; Pathology » Marc Rothenberg, MD, PhD; J Pablo Abonia, MD, PhD; Keith Marsolo, PhD; Margaret Collins, MD
Eosinophilic Esophagitis Comparative Effectiveness - James Franciosi, MD
Allergy & Immunology; Neonatology & Pulmonary Biology; Developmental Biology » Simon Hogan, PhD; Jeffrey Whitsett, MD; James Wells, PhD
iPSC-derived intestinal tissue from CF patients - Noah Shroyer, PhD
Developmental Biology » James Wells, PhD
In vitro growth and differentiation of gastrointestinal tissue from human pluripotent stem cells - Noah Shroyer, PhD
Neonatology & Pulmonary Biology » Jeffrey Whitsett, MD
Transcriptional control of intestinal differentiation an neoplasia by SPDEF - Noah  Shroyer, PhD
Neonatology & Pulmonary Biology; Developmental Biology » Jeffrey Whitsett, MD; James Wells, PhD
KLF5 control of gastrointestinal morphogenesis and stem cell homeostasis - Noah  Shroyer, PhD
Pediatric Surgery; Developmental Biology » Michael Helmrath, MD; James Wells, PhD
Mesenchymal control of intestinal stem cells - Noah Shroyer, PhD
Pulmonary Medicine; Radiology » John Clancy, MD; Alexander Towbin, MD
Identifying early markers of liver disease in patients with cystic fibrosis - Joseph  Palermo, MD, PhD

Faculty Members

Mitchell B Cohen, MD, Professor
Gastroenterology Endowed Chair
Vice-Chair of Pediatrics for Clinical Affairs
Director, Division of Gastroenterology, Hepatology and Nutrition
Associate Director, Digestive Health Center
Research Interests Diarrheal diseases
William F Balistreri, MD, Professor
Dorothy M.M. Kersten Endowed Chair
Director Emeritus, Pediatric Liver Care Center
Medical Director Emeritus, Liver Transplantation
Program Director, Advanced Hepatology Fellowship
Editor, Journal of Pediatrics
Research Interests Chronic liver disease
Jorge A Bezerra, MD, Professor
William and Rebecca Balistreri Chair in Pediatric Hepatology
Director of Research, Division of Gastroenterology, Hepatology and Nutrition
Director, Biliary Atresia Center
Director, Digestive Health Center
Research Interests Biliary atresia and chronic liver disease
John C Bucuvalas, MD, Professor
Endowed Chair in Pediatric Transplant Hepatology
Associate Medical Director, Pediatric Liver Care Center
Director, Disease Specific Innovations and Outcomes Program
Research Interests Liver failure and liver transplantation
Kathleen M Campbell, MD, Assistant Professor
Medical Director, Pediatric Liver Transplant
Research Interests Liver failure and liver transplantation
Conrad R Cole, MD, Associate Professor
Associate Medical Director, Intestinal Rehabilitation Program
Research Interests Intestinal failure
Lee A Denson, MD, Associate Professor
M. Susan Moyer Chair in Pediatric IBD
Director, Schubert-Martin Pediatric IBD Center
Director, Fellowship Training Program in Pediatric Gastroenterology, Hepatology and Nutrition
Research Interests Inflammatory Bowel Diseases
Michael K Farrell, MD, Professor
Chief of Staff
Research Interests Nutrition
James Franciosi, MD, Assistant Professor
Research Interests Eosinophilic Gastrointestinal Disorders
Jose Garza, MD, Assistant Professor
Research Interests Neurogastroenterological disorders
Xiaonan Han, PhD, Assistant Professor
Research Interests Inflammatory Bowel Diseases
James E Heubi, MD, Professor
Associate Chair for Clinical Investigation of Pediatrics
Associate Dean for Clinical and Translational Research
Co-Director, Center of Clinical and Translational Science & Training
Research Interests Chronic liver disease
Ajay Kaul, MD, Associate Professor
Director, Impedance/Motility Disorders Program
Medical Director, Liberty Campus for GI
Research Interests Intestinal motility disorders
Samuel A Kocoshis, MD, Professor
Medical Director, Pediatric Nutritional and Intestinal Care Center
Medical Director, Small Bowel Transplantation Program
Research Interests Intestinal Failure and Intestinal Transplantation
Rohit Kohli, MD, Assistant Professor
Co-Director, Steatohepatitis Center
Research Interests Non-alcoholic steatohepatitis
Mike A Leonis, MD, PhD, Assistant Professor
Associate Fellowship Director, Training Program in Pediatric Gastroenterology, Hepatology and Nutrition
Research Interests Liver failure and liver transplantation; liver tumors
Adam G Mezoff, MD, Professor
Associate Medical Director, Pediatric Nutritional and Intestinal Care Center
Clinical Director for Gastroenterology
Research Interests Intestinal failure and intestinal transplantation
Alexander Miethke, MD, Assistant Professor
Research Interests Biliary atresia and primary sclerosing cholangitis
Sean Moore, MD, Assistant Professor
Research Interests Diarrheal Diseases and International Health
Joseph Palermo, MD, PhD, Assistant Professor
Research Interests Disorders of the bile ducts
Scott Pentiuk, MD, Assistant Professor
Pediatric Residency Course Director for Gastroenterology
Research Interests Feeding disorders; medical education
Philip E Putnam, MD, Professor
Director, Endoscopy Services
Medical Director, Cincinnati Center for Eosinophilic Disorders
Research Interests Eosinophilic Gastrointestinal Disorders
Shehzad A Saeed, MD, Associate Professor
Associate Director, GI Fellowship Program
Clinical Director of the Schubert-Martin IBD Center
Research Interests Inflammatory Bowel Disease
Charles Samson, MD, Instructor
Research Interests Inflammatory Bowel Disease
Pranav Shivakumar, PhD, Assistant Professor
Research Interests Biliary Atresia
Noah Shroyer, PhD, Assistant Professor
Research Interests Intestinal development
Kris Steinbrecher, PhD, Assistant Professor
Research Interests Diarrheal diseases; Inflammatory Bowel Diseases
Cynthia C Wetzel, PhD, Assistant Professor
Program Manager, Digestive Health Center
Research Interests Research Administration
Stavra Xanthakos, MD, Assistant Professor
Medical Director, Surgical Weight Loss Program for Teens
Co-Director, Steatohepatitis Center
Research Interests Obesity; Non-alcoholic steatohepatitis
Nada Yazigi, MD, Associate Professor
Associate Medical Director, Multivisceral Transplantation Program
CSI Inpatient Co-Director, A4N
Research Interests Liver failure and liver transplantation

Trainees

  • M Kyle Jenson, MD, PL-7, Children's Hospital and Health System and the Medical College of Wisconsin
  • Stephanie Appleman, MD, PL-6, INOVA Fairfax Hospital for Children
  • Benjamin Kuhn, DO, PL-6, Penn State Children's Hospital
  • Anna Trauernicht, MD, PL-6, Indiana University
  • Amy Tsai, MD, PL-6, New York Medical College
  • Frank Dipaola, MD, PL-5, Vanderbilt Children's Hospital
  • Dana Dykes, MD, PL-5, Children's Hospital at UAB
  • Jaime Echartea-Gonzalez, MD, PL-5, Cincinnati Children's Hospital Medical Center
  • Kristin Bramlage, MD, PL-5, NS-LIJ Health System
  • Monique Choquette, MD, PL-4, Cincinnati Children's Hospital Medical Center
  • Phillip Minar, MD, PL-4, Medical College of Wisconsin
  • George Zacur, MD, PL-4, University of Miami/Jackson Memorial Hospital
  • Kazuhiko Bessho, MD, PhD, Osaka University, Japan
  • Ingrid Jurickova, MD, Second Medical Faculty, Charles University, Prague, Czech Republic
  • Jun Li, MD, PhD, Beijing Medical University and Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
  • Elizabeth Mann, PhD, State University of New York at Buffalo
  • Taeko Noah, PhD, University of Nevada, Reno
  • Vijay Saxena, PhD, Kanpur University, India
  • Celine Silva-Lages, PhD, University Paris Diderot, Paris 7, Paris, France
  • Samir Softic, MD, Wright State University - Boonshoft School of Medicine, Dayton, Ohio
  • Tara Willson, BS, University of Kentucky, Lexington
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Significant Accomplishments

The Chronic Liver Disease Program

Staffed by nine pediatric hepatologists, the Chronic Liver Disease Program serves a national and international referral population via a comprehensive evaluation of all medical and surgical aspects of liver disease and offers prompt initiation of conventional and innovative treatments. The evaluation includes a full spectrum of metabolic analysis, inflammatory processes and high-throughput gene sequencing to screen for genetic diseases. The clinic allows for timely consultation with surgeons, pathologists, radiologists and nutritionists with expertise in pediatric liver disease, thus enabling a thorough evaluation of the impact of the illness on the child’s well-being. For children with advanced stages of liver disease, an evaluation for liver transplantation and close follow-up in the pre-transplant clinic enable the implementation of the most comprehensive treatment protocol to minimize complications and improve post-transplant course.

Recognizing that research is critical to improved care, clinic staff members lead multicenter studies sponsored by the National Institutes of Health to advance knowledge on mechanisms of pediatric liver disease and to develop diagnostic and treatment modalities. Recent innovations include: 1) the development of a high-throughput gene chip to diagnose mutations in children with genetic liver diseases, 2) an ongoing trial to determine the efficacy of corticosteroids in children with biliary atresia, 3) a study to examine the role of immune dysregulation in the etiology of acute liver failure, 4) studies to discover biomarkers and therapies for fatty liver disease, and 5) the development of therapies for bile acid disorders. The clinical and research programs create an outstanding environment for the training of future leaders in the field via a fellowship training program in advanced hepatology. 

Intestinal Rehabilitation Program 

The Intestinal Rehabilitation Program has experienced considerable growth during the past year to position itself for a national leadership role in conducting basic scientific, translational and clinical research. The multidisciplinary initiative to standardize care and facilitate research among the three disciplines (gastroenterology, neonatology and surgery) providing care to infants and children with intestinal failure was implemented. Currently the rate of survival without significant liver disease (as measured by cholestasis) of our patients with intestinal failure is among the highest nationally. Major clinical initiatives include weekly multidisciplinary bedside rounds; development of a specific emergency department protocol for standardized evaluation and treatment of fevers among children with central venous catheters; and pre-clinic planning meetings, which are expected to improve the patient’s clinic experience. In addition, we have protocolized management of central venous catheters with suspected bacterial biofilms by initiating ethanol lock therapy and laboratory assessment of nutritional markers. These initiatives have significantly reduced the incidence of outpatient acquired central line bloodstream infections.

Translational and clinical trials research initiatives were also implemented. These include evaluating the relative value of biomarkers of infection (sTREMs [triggering receptors of myeloid cells] and LBP [lipoprotein binding protein]) for identifying acute bloodstream infections (BSI) and for predicting need for liver/bowel transplant and death among our population on total parenteral nutrition (TPN). Other studies include developing in vitro culture methods to grow and expand both normal and diseased intestinal tissue from patients with intestinal failure; validating the use of bomb calorimetry as a measure of enteral energy balance among intestinal failure patients; and feeding advancement trial in patients with gastroschisis to identify the method that optimally decreases the duration of TPN. We continue participation in the 15-center Pediatric Intestinal Failure Consortium and are in the process of analyzing data describing factors impacting outcomes in pediatric intestinal failure.

Inflammatory Bowel Disease

The number of patients receiving multidisciplinary care for IBD has continued to grow, with children from more than 25 states seen over the past year. State-of-the art services including diagnostic imaging modalities, which do not require radiation exposure, and targeted psychology interventions for nonadherence have been implemented. We have continued to contribute to international genome-wide association studies to identify susceptibility genes specifically for pediatric-onset disease. Investigators have received funding from the National Institutes of Health (NIH) to develop the first multicenter North American randomized controlled trial in newly diagnosed children with ulcerative colitis, the PROTECT study.  Within this trial, we will develop a model to predict individual patient therapeutic responses and clinic outcomes that will incorporate clinical, genetic and immune biomarkers that we have developed.  At Cincinnati Children’s, this trial will include collaborators in the Divisions of Pulmonary Biology and Biomedical Informatics.  Under the leadership of Kevin Hommel, PhD, in the Adherence Center, we will be one of three centers to participate in the first randomized controlled trial of telehealth interventions to improve medication adherence in children with IBD.  

It is anticipated that the knowledge gained from these studies will be rapidly translated to practice through our collaborations with Peter Margolis, MD, PhD, in clinical effectiveness, via his leadership of the ImproveCareNow (ICN) pediatric IBD quality improvement network.  The IBD Center has continued to play a leading role in ICN, which has achieved a 20 percent improvement in patient remission rates with implementation of consensus patient care guidelines and practices. This network was the basis for an NIH award to Margolis in the Center for Health Care Quality to develop an innovative web-based social networking model to improve outcomes for children with IBD, termed C3N. As part of this collaborative network, patient-focused activities are being developed to improve patient outcomes and engage patients and their families to become more involved in the care of their IBD. A pilot trial of daily symptom assessment using innovative bioinformatics tools was undertaken with the patient participating in daily and weekly surveys of the symptoms and QOL measures.

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Division Publications

  1. Abonia JP, Blanchard C, Butz BB, Rainey HF, Collins MH, Stringer K, Putnam PE, Rothenberg ME. Involvement of mast cells in eosinophilic esophagitis. J Allergy Clin Immunol. 2010; 126:140-9.
  2. A-Kadar Hassan H, Balistreri WF. Cholestasis. Nelson Textbook of Pediatrics. Philadelphia: W.B. Saunders Company; 2011: 168-176. .
  3. Alkhouri N, Franciosi JP, Mamula P. Familial adenomatous polyposis in children and adolescents. J Pediatr Gastroenterol Nutr. 2010; 51:727-32.
  4. Anderson CA, Boucher G, Lees CW, Franke A, D'Amato M, Taylor KD, Lee JC, Goyette P, Imielinski M, Latiano A, Lagace C, Scott R, Amininejad L, Bumpstead S, Baidoo L, Baldassano RN, Barclay M, Bayless TM, Brand S, Buning C, Colombel JF, Denson LA, De Vos M, Dubinsky M, Edwards C, Ellinghaus D, Fehrmann RS, Floyd JA, Florin T, Franchimont D, Franke L, Georges M, Glas J, Glazer NL, Guthery SL, Haritunians T, Hayward NK, Hugot JP, Jobin G, Laukens D, Lawrance I, Lemann M, Levine A, Libioulle C, Louis E, McGovern DP, Milla M, Montgomery GW, Morley KI, Mowat C, Ng A, Newman W, Ophoff RA, Papi L, Palmieri O, Peyrin-Biroulet L, Panes J, Phillips A, Prescott NJ, Proctor DD, Roberts R, Russell R, Rutgeerts P, Sanderson J, Sans M, Schumm P, Seibold F, Sharma Y, Simms LA, Seielstad M, Steinhart AH, Targan SR, van den Berg LH, Vatn M, Verspaget H, Walters T, Wijmenga C, Wilson DC, Westra HJ, Xavier RJ, Zhao ZZ, Ponsioen CY, Andersen V, Torkvist L, Gazouli M, Anagnou NP, Karlsen TH, Kupcinskas L, Sventoraityte J, Mansfield JC, Kugathasan S, Silverberg MS, Halfvarson J, Rotter JI, Mathew CG, Griffiths AM, Gearry R, Ahmad T, Brant SR, Chamaillard M, Satsangi J, Cho JH, Schreiber S, Daly MJ, Barrett JC, Parkes M, Annese V, Hakonarson H, Radford-Smith G, Duerr RH, Vermeire S, Weersma RK, Rioux JD. Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47. Nat Genet. 2011; 43:246-52.
  5. Bessho K, Bezerra JA. Biliary atresia: will blocking inflammation tame the disease?. Annu Rev Med. 2011; 62:171-85.
  6. Beuling E, Baffour-Awuah NY, Stapleton KA, Aronson BE, Noah TK, Shroyer NF, Duncan SA, Fleet JC, Krasinski SD. GATA factors regulate proliferation, differentiation, and gene expression in small intestine of mature mice. Gastroenterology. 2011; 140:1219-1229 e1-2.
  7. Bezerra J. Biliary atresia. Molecular Pathology of Liver Diseases. Springer; 2010: 753-765. .
  8. Bischoff A, Gupta A, D'Mello S, Mezoff A, Podberesky D, Barnett S, Keswani S, Frischer JS. Crohn's disease limited to the appendix: a case report in a pediatric patient. Pediatr Surg Int. 2010; 26:1125-8.
  9. Blanchard C, Stucke EM, Rodriguez-Jimenez B, Burwinkel K, Collins MH, Ahrens A, Alexander ES, Butz BK, Jameson SC, Kaul A, Franciosi JP, Kushner JP, Putnam PE, Abonia JP, Rothenberg ME. A striking local esophageal cytokine expression profile in eosinophilic esophagitis. J Allergy Clin Immunol. 2011; 127:208-17, 217 e1-7.
  10. Boamah LM, Balistreri WF. Manifestations of Liver Disease. Nelson Textbook of Pediatrics. Philadelphia: W.B. Saunders Company; 2011: 162-168. .
  11. Boamah LM, Bohren JR, Pentiuk S, Baker R, Yi M, Moyer MS. Development and testing of a CD-ROM program for improving adolescent knowledge of inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 2010; 50:521-5.
  12. Brunt EM, Kleiner DE, Wilson LA, Belt P, Neuschwander-Tetri BA, Xanthakos S. Nonalcoholic fatty liver disease (NAFLD) activity score and the histopathologic diagnosis in NAFLD: distinct clinicopathologic meanings. Hepatology. 2011; 53:810-20.
  13. Campbell K, Ng V, Martin S, Magee J, Goebel J, Anand R, Martz K, Bucuvalas J. Glomerular filtration rate following pediatric liver transplantation--the SPLIT experience. Am J Transplant. 2010; 10:2673-82.
  14. Campbell KM, Bucuvalas JC. Renal function in the long term after pediatric liver transplantation: is there a need for protocol kidney biopsies?. Curr Opin Organ Transplant. 2010; 15:608-13.
  15. Carey R, Balistreri WF. Metabolic Diseases of the Liver. Nelson Textbook of Pediatrics. Philadelphia: W.B. Saunders Company; 2011: 176-181. .
  16. Carey R, Balistreri WF. Mitochondrial Hepatopathies. Nelson Textbook of Pediatrics. Philadelphia: W.B. Saunders Company; 2011: 197-199. .
  17. Carter-Kent C, Brunt EM, Yerian LM, Alkhouri N, Angulo P, Kohli R, Ling SC, Xanthakos SA, Whitington PF, Charatcharoenwitthaya P, Yap J, Lopez R, McCullough AJ, Feldstein AE. Relations of steatosis type, grade, and zonality to histological features in pediatric nonalcoholic fatty liver disease. J Pediatr Gastroenterol Nutr. 2011; 52:190-7.
  18. Crandall W, Kappelman MD, Colletti RB, Leibowitz I, Grunow JE, Ali S, Baron HI, Berman JH, Boyle B, Cohen S, del Rosario F, Denson LA, Duffy L, Integlia MJ, Kim SC, Milov D, Patel AS, Schoen BT, Walkiewicz D, Margolis P. ImproveCareNow: The development of a pediatric inflammatory bowel disease improvement network. Inflamm Bowel Dis. 2011; 17:450-7.
  19. Crawford LC, Crawford ML, Moore SR. Hemolytic-uremic syndrome in a grandmother. Emerg Infect Dis. 2010; 16:1792-5.
  20. Day SB, Kocoshis SA. Disorders and Diseases of the Gastrointestinal Tract and Liver. Pediatric Critical Care. Mosby; 2011: 1221-1233. .
  21. DeBrosse CW, Collins MH, Buckmeier Butz BK, Allen CL, King EC, Assa'ad AH, Abonia JP, Putnam PE, Rothenberg ME, Franciosi JP. Identification, epidemiology, and chronicity of pediatric esophageal eosinophilia, 1982-1999. J Allergy Clin Immunol. 2010; 126:112-9.
  22. Denson LA, Kim MO, Bezold R, Carey R, Osuntokun B, Nylund C, Willson T, Bonkowski E, Li D, Ballard E, Collins M, Moyer MS, Klein DJ. A randomized controlled trial of growth hormone in active pediatric Crohn disease. J Pediatr Gastroenterol Nutr. 2010; 51:130-9.
  23. Dotson JL, Crandall W, Mousa H, Honegger JR, Denson L, Samson C, Cunningham D, Balint J, Dienhart M, Jaggi P, Carvalho R. Presentation and outcome of histoplasmosis in pediatric inflammatory bowel disease patients treated with antitumor necrosis factor alpha therapy: a case series. Inflamm Bowel Dis. 2011; 17:56-61.
  24. Evason K, Bove KE, Finegold MJ, Knisely AS, Rhee S, Rosenthal P, Miethke AG, Karpen SJ, Ferrell LD, Kim GE. Morphologic findings in progressive familial intrahepatic cholestasis 2 (PFIC2): correlation with genetic and immunohistochemical studies. Am J Surg Pathol. 2011; 35:687-96.
  25. Fernandez KS, Baum R, Fung B, Yeager N, Leonis MA, Wagner LM, Tiao G, Ross ME. Chemoresistant hepatoblastoma in a patient with mosaic trisomy 18 treated with orthotopic liver transplantation. Pediatr Blood Cancer. 2011; 56:498-500.
  26. Franciosi JP, Fiorino K, Ruchelli E, Shults J, Spergel J, Liacouras CA, Leonard M. Changing indications for upper endoscopy in children during a 20-year period. J Pediatr Gastroenterol Nutr. 2010; 51:443-7.
  27. Freed GL, Dunham KM, Gebremariam A, Wheeler JR, Balistreri W. Which pediatricians are providing care to America's children? An update on the trends and changes during the past 26 years. J Pediatr. 2010; 157:148-152 e1.
  28. Freed GL, Dunham KM, Lamarand KE, Loveland-Cherry C, Martyn KK, Balistreri W. Neonatal nurse practitioners: distribution, roles and scope of practice. Pediatrics. 2010; 126:856-60.
  29. Freed GL, Dunham KM, Lamarand KE, Loveland-Cherry C, Martyn KK, Balistreri W. Pediatric nurse practitioners: roles and scope of practice. Pediatrics. 2010; 126:846-50.
  30. Freed GL, Dunham KM, Loveland-Cherry C, Martyn KK, Balistreri W. Family nurse practitioners: roles and scope of practice in the care of pediatric patients. Pediatrics. 2010; 126:861-4.
  31. Freed GL, Dunham KM, Loveland-Cherry CJ, Martyn KK, Balistreri W. Pediatric nurse practitioners in the United States: current distribution and recent trends in training. J Pediatr. 2010; 157:589-93, 593 e1.
  32. Freed GL, Dunham KM, Moote MJ, Lamarand KE, Balistreri W. Pediatric physician assistants: distribution and scope of practice. Pediatrics. 2010; 126:851-5.
  33. Garza JM, Cohen MB. Infectious Diarrhea. Pediatric Gastrointestinal and Liver Disease. Philadelphia: W.B. Saunders Company; 2010: 405-422. .
  34. Garza JM, Kaul A. Gastroesophageal reflux, eosinophilic esophagitis, and foreign body. Pediatr Clin North Am. 2010; 57:1331-45.
  35. Gerbe F, van Es JH, Makrini L, Brulin B, Mellitzer G, Robine S, Romagnolo B, Shroyer NF, Bourgaux JF, Pignodel C, Clevers H, Jay P. Distinct ATOH1 and Neurog3 requirements define tuft cells as a new secretory cell type in the intestinal epithelium. J Cell Biol. 2011; 192:767-80.
  36. Han X, Gilbert S, Groschwitz K, Hogan S, Jurickova I, Trapnell B, Samson C, Gully J. Loss of GM-CSF signalling in non-haematopoietic cells increases NSAID ileal injury. Gut. 2010; 59:1066-78.
  37. Han X, Mann E, Gilbert S, Guan Y, Steinbrecher KA, Montrose MH, Cohen MB. Loss of guanylyl cyclase C (GCC) signaling leads to dysfunctional intestinal barrier. PLoS One. 2011; 6:e16139.
  38. Herzer M, Denson LA, Baldassano RN, Hommel KA. Family functioning and health-related quality of life in adolescents with pediatric inflammatory bowel disease. Eur J Gastroenterol Hepatol. 2011; 23:95-100.
  39. Herzer M, Denson LA, Baldassano RN, Hommel KA. Patient and parent psychosocial factors associated with health-related quality of life in pediatric inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 2011; 52:295-9.
  40. Heubi JE. Bile Acid Physiology and Alterations in the Enterohepatic Circulation. Pediatric Gastrointestinal and Liver Disease. Philadelphia: W.B. Saunders Company; 2010: 20-27. .
  41. Hocking MC, Barnes M, Shaw C, Lochman JE, Madan-Swain A, Saeed S. Executive function and attention regulation as predictors of coping success in youth with functional abdominal pain. J Pediatr Psychol. 2011; 36:64-73.
  42. Hommel KA, Denson LA, Baldassano RN. Oral medication adherence and disease severity in pediatric inflammatory bowel disease. Eur J Gastroenterol Hepatol. 2011; 23:250-4.
  43. Hyams JS, Lerer T, Mack D, Bousvaros A, Griffiths A, Rosh J, Otley A, Evans J, Stephens M, Kay M, Keljo D, Pfefferkorn M, Saeed S, Crandall W, Michail S, Kappelman MD, Grossman A, Samson C, Sudel B, Oliva-Hemker M, Leleiko N, Markowitz J. Outcome following thiopurine use in children with ulcerative colitis: a prospective multicenter registry study. Am J Gastroenterol. 2011; 106:981-7.
  44. Ingerski LM, Baldassano RN, Denson LA, Hommel KA. Barriers to oral medication adherence for adolescents with inflammatory bowel disease. J Pediatr Psychol. 2010; 35:683-91.
  45. Kaul A, Garza JM, Connor FL, Cocjin JT, Flores AF, Hyman PE, Di Lorenzo C. Colonic hyperactivity results in frequent fecal soiling in a subset of children after surgery for Hirschsprung disease. J Pediatr Gastroenterol Nutr. 2011; 52:433-6.
  46. Kazanjian A, Noah T, Brown D, Burkart J, Shroyer NF. Atonal homolog 1 is required for growth and differentiation effects of notch/gamma-secretase inhibitors on normal and cancerous intestinal epithelial cells. Gastroenterology. 2010; 139:918-28, 928 e1-6.
  47. Kohli R, Kirby M, Setchell KD, Jha P, Klustaitis K, Woollett LA, Pfluger PT, Balistreri WF, Tso P, Jandacek RJ, Woods SC, Heubi JE, Tschoep MH, D'Alessio DA, Shroyer NF, Seeley RJ. Intestinal adaptation after ileal interposition surgery increases bile acid recycling and protects against obesity-related comorbidities. Am J Physiol Gastrointest Liver Physiol. 2010; 299:G652-60.
  48. Kohli R, Kirby M, Xanthakos SA, Softic S, Feldstein AE, Saxena V, Tang PH, Miles L, Miles MV, Balistreri WF, Woods SC, Seeley RJ. High-fructose, medium chain trans fat diet induces liver fibrosis and elevates plasma coenzyme Q9 in a novel murine model of obesity and nonalcoholic steatohepatitis. Hepatology. 2010; 52:934-44.
  49. Kuhn BR, Mezoff A. Bezoars. Pediatric Gastrointestinal and Liver Disease. Philadelphia: W.B. Saunders Company; 2010: 319-322. .
  50. Lawal TA, Falcone RA, von Allmen D, Denson LA, Levitt MA, Warner BW, Frischer JS. The utility of routine pouchogram before ileostomy reversal in children and adolescents following ileal pouch anal anastomosis. J Pediatr Surg. 2011; 46:1222-5.
  51. Lawal TA, Frischer JS, Falcone RA, Chatoorgoon K, Denson LA, Levitt MA. The transanal approach with laparoscopy or laparotomy for the treatment of rectal strictures in Crohn's disease. J Laparoendosc Adv Surg Tech A. 2010; 20:791-5.
  52. Limbers CA, Neighbors K, Martz K, Bucuvalas JC, Webb T, Varni JW, Alonso EM. Health-related quality of life in pediatric liver transplant recipients compared with other chronic disease groups. Pediatr Transplant. 2011; 15:245-53.
  53. Mann EA, Shanmukhappa K, Cohen MB. Lack of guanylate cyclase C results in increased mortality in mice following liver injury. BMC Gastroenterol. 2010; 10:86.
  54. Matte U, Mourya R, Miethke A, Liu C, Kauffmann G, Moyer K, Zhang K, Bezerra JA. Analysis of gene mutations in children with cholestasis of undefined etiology. J Pediatr Gastroenterol Nutr. 2010; 51:488-93.
  55. McLin V, Yazigi N. Developmental Anatomy and Physiology of the Liver and Bile Ducts. Pediatric Gastrointestinal and Liver Disease. Philadelphia: W.B. Saunders Company; 2010: 718-727. .
  56. Mezoff E, Cohen MB. Clostridium difficile Infection. Nelson Textbook of Pediatrics. Philadelphia: W.B. Saunders Company; 2011.
  57. Mezoff E, Mann EA, Hart KW, Lindsell CJ, Cohen MB. Clostridium difficile infection and treatment in the pediatric inflammatory bowel disease population. J Pediatr Gastroenterol Nutr. 2011; 52:437-41.
  58. Miethke A, Balistreri WF. Morphogenesis of the Liver and Biliary System. Nelson Textbook of Pediatrics. Philadelphia: W.B. Saunders Company; 2011: 158-161. .
  59. Miles MV, Putnam PE, Miles L, Tang PH, DeGrauw AJ, Wong BL, Horn PS, Foote HL, Rothenberg ME. Acquired coenzyme Q10 deficiency in children with recurrent food intolerance and allergies. Mitochondrion. 2011; 11:127-35.
  60. Mizukawa B, George A, Pushkaran S, Weckbach L, Kalinyak K, Heubi JE, Kalfa TA. Cooperating G6PD mutations associated with severe neonatal hyperbilirubinemia and cholestasis. Pediatr Blood Cancer. 2011; 56:840-2.
  61. Moore SR. Update on prolonged and persistent diarrhea in children. Curr Opin Gastroenterol. 2011; 27:19-23.
  62. Moore SR, Lima NL, Soares AM, Oria RB, Pinkerton RC, Barrett LJ, Guerrant RL, Lima AA. Prolonged episodes of acute diarrhea reduce growth and increase risk of persistent diarrhea in children. Gastroenterology. 2010; 139:1156-64.
  63. Moyer KD, Balistreri WF. Liver Disease Associated with Systemic Disorders. Nelson Textbook of Pediatrics. Philadelphia: W.B. Saunders Company; 2011: 193-196. .
  64. Munitz A, Cole ET, Beichler A, Groschwitz K, Ahrens R, Steinbrecher K, Willson T, Han X, Denson L, Rothenberg ME, Hogan SP. Paired immunoglobulin-like receptor B (PIR-B) negatively regulates macrophage activation in experimental colitis. Gastroenterology. 2010; 139:530-41.
  65. Narkewicz MR, Rosenthal P, Schwarz KB, Drack A, Margolis T, Repka MX, Balistreri W. Ophthalmologic complications in children with chronic hepatitis C treated with pegylated interferon. J Pediatr Gastroenterol Nutr. 2010; 51:183-6.
  66. Nylund CM, D'Mello S, Kim MO, Bonkowski E, Dabritz J, Foell D, Meddings J, Trapnell BC, Denson LA. Granulocyte macrophage-colony-stimulating factor autoantibodies and increased intestinal permeability in Crohn disease. J Pediatr Gastroenterol Nutr. 2011; 52:542-8.
  67. Nylund CM, Goudie A, Garza JM, Fairbrother G, Cohen MB. Clostridium difficile infection in hospitalized children in the United States. Arch Pediatr Adolesc Med. 2011; 165:451-7.
  68. Odell S, Sander E, Denson LA, Baldassano RN, Hommel KA. The contributions of child behavioral functioning and parent distress to family functioning in pediatric inflammatory bowel disease. J Clin Psychol Med Settings. 2011; 18:39-45.
  69. Peignon G, Durand A, Cacheux W, Ayrault O, Terris B, Laurent-Puig P, Shroyer NF, Van Seuningen I, Honjo T, Perret C, Romagnolo B. Complex interplay between beta-catenin signalling and Notch effectors in intestinal tumorigenesis. Gut. 2011; 60:166-76.
  70. Pentiuk S, O'Flaherty T, Santoro K, Willging P, Kaul A. Pureed by gastrostomy tube diet improves gagging and retching in children with fundoplication. JPEN J Parenter Enteral Nutr. 2011; 35:375-9.
  71. Phelan JD, Shroyer NF, Cook T, Gebelein B, Grimes HL. Gfi1-cells and circuits: unraveling transcriptional networks of development and disease. Curr Opin Hematol. 2010; 17:300-7.
  72. Rodrigue JR, Balistreri W, Haber B, Jonas MM, Mohan P, Molleston JP, Murray KF, Narkewicz MR, Rosenthal P, Smith LJ, Lobritto SJ, Schwarz KB, Robuck PR, Barton B, Gonzalez-Peralta RP. Peginterferon with or without ribavirin has minimal effect on quality of life, behavioral/emotional, and cognitive outcomes in children. Hepatology. 2011; 53:1468-75.
  73. Saeed S, Boyle J. Other Diseases of the Esophagus. Pediatric Gastrointestinal and Liver Disease. Philadelphia: W.B. Saunders Company; 2010: 255-261. .
  74. Schaefer ME, Machan JT, Kawatu D, Langton CR, Markowitz J, Crandall W, Mack DR, Evans JS, Pfefferkorn MD, Griffiths AM, Otley AR, Bousvaros A, Kugathasan S, Rosh JR, Keljo DJ, Carvalho RS, Tomer G, Mamula P, Kay MH, Kerzner B, Oliva-Hemker M, Kappelman MD, Saeed SA, Hyams JS, Leleiko NS. Factors that determine risk for surgery in pediatric patients with Crohn's disease. Clin Gastroenterol Hepatol. 2010; 8:789-94.
  75. Schwarz KB, Gonzalez-Peralta RP, Murray KF, Molleston JP, Haber BA, Jonas MM, Rosenthal P, Mohan P, Balistreri WF, Narkewicz MR, Smith L, Lobritto SJ, Rossi S, Valsamakis A, Goodman Z, Robuck PR, Barton BA. The combination of ribavirin and peginterferon is superior to peginterferon and placebo for children and adolescents with chronic hepatitis C. Gastroenterology. 2011; 140:450-458 e1.
  76. Sherrill JD, Gao PS, Stucke EM, Blanchard C, Collins MH, Putnam PE, Franciosi JP, Kushner JP, Abonia JP, Assa'ad AH, Kovacic MB, Biagini Myers JM, Bochner BS, He H, Hershey GK, Martin LJ, Rothenberg ME. Variants of thymic stromal lymphopoietin and its receptor associate with eosinophilic esophagitis. J Allergy Clin Immunol. 2010; 126:160-5 e3.
  77. Shroyer NF, Kocoshis SA. Anatomy and Physiology of the Small and Large Intestines. Pediatric Gastrointestinal and Liver Disease. Philadelphia: W.B. Saunders Company; 2010: 324-336. .
  78. Sorensen LG, Neighbors K, Martz K, Zelko F, Bucuvalas JC, Alonso EM. Cognitive and academic outcomes after pediatric liver transplantation: Functional Outcomes Group (FOG) results. Am J Transplant. 2011; 11:303-11.
  79. Spence JR, Lauf R, Shroyer NF. Vertebrate intestinal endoderm development. Dev Dyn. 2011; 240:501-20.
  80. Spence JR, Mayhew CN, Rankin SA, Kuhar MF, Vallance JE, Tolle K, Hoskins EE, Kalinichenko VV, Wells SI, Zorn AM, Shroyer NF, Wells JM. Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro. Nature. 2011; 470:105-9.
  81. Steinbrecher KA, Cohen MB. Transmembrane guanylate cyclase in intestinal pathophysiology. Curr Opin Gastroenterol. 2011; 27:139-45.
  82. Steinbrecher KA, Harmel-Laws E, Garin-Laflam MP, Mann EA, Bezerra LD, Hogan SP, Cohen MB. Murine guanylate cyclase C regulates colonic injury and inflammation. J Immunol. 2011; 186:7205-14.
  83. Stuart WD, Kulkarni RM, Gray JK, Vasiliauskas J, Leonis MA, Waltz SE. Ron receptor regulates Kupffer cell-dependent cytokine production and hepatocyte survival following endotoxin exposure in mice. Hepatology. 2011; 53:1618-28.
  84. Thayu M, Denson LA, Shults J, Zemel BS, Burnham JM, Baldassano RN, Howard KM, Ryan A, Leonard MB. Determinants of changes in linear growth and body composition in incident pediatric Crohn's disease. Gastroenterology. 2010; 139:430-8.
  85. Waddell A, Ahrens R, Steinbrecher K, Donovan B, Rothenberg ME, Munitz A, Hogan SP. Colonic eosinophilic inflammation in experimental colitis is mediated by Ly6C(high) CCR2(+) inflammatory monocyte/macrophage-derived CCL11. J Immunol. 2011; 186:5993-6003.
  86. Wu D, Ahrens R, Osterfeld H, Noah TK, Groschwitz K, Foster PS, Steinbrecher KA, Rothenberg ME, Shroyer NF, Matthaei KI, Finkelman FD, Hogan SP. Interleukin-13 (IL-13)/IL-13 receptor alpha1 (IL-13Ralpha1) signaling regulates intestinal epithelial cystic fibrosis transmembrane conductance regulator channel-dependent Cl- secretion. J Biol Chem. 2011; 286:13357-69.
  87. Yarandi SS, Hebbar G, Sauer CG, Cole CR, Ziegler TR. Diverse roles of leptin in the gastrointestinal tract: modulation of motility, absorption, growth, and inflammation. Nutrition. 2011; 27:269-75.
  88. Yazigi N, Balistreri W. Viral Hepatitis. Nelson Textbook of Pediatrics. Philadelphia: W.B Saunders Company; 2011.
  89. Zhu X, Wang M, Mavi P, Rayapudi M, Pandey AK, Kaul A, Putnam PE, Rothenberg ME, Mishra A. Interleukin-15 expression is increased in human eosinophilic esophagitis and mediates pathogenesis in mice. Gastroenterology. 2010; 139:182-93 e7.
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Grants, Contracts, and Industry Agreements

Grant and Contract AwardsAnnual Direct / Project Period Direct

Bezerra, J

Clinical Center for Cholestatic Liver Disease in Children
U01 DK 06249709/10/09-05/31/14$489,645
Bezerra, J.Administrative Core$394,826
Bezerra, J.RNA Core$30,810
Heubi, J.Bile Acid Core$29,808
Bove, K.Histopathology Core$34,201
Biological Basis of Phenotypes & Clinical Outcomes in Biliary Atresia
R01 DK 08378109/01/09-08/31/13$237,600
Digestive Health Center: Bench to Beside Research in Pediatric Digestive Disease
P30 DK 07839208/01/07-05/31/12$843,422
Bezerra, J.Administrative Core$373,722
Witte, D.Integrative Morphology Core$114,769
Potter, S.Gene Expression Core$54,717
Grabowski, G.Sequencing Core$21,466
Aronow, B.Bioinformatics Core$110,942
Wills-Karp, M.Luminex Service$38,792
Bezerra, J.Flow Cytometry Service$29,014
Diavanovic, S.Pilot & Feasibility Grant$50,000
Spence, J.Pilot & Feasibility Grant$50,000
Immunologic Dsyfunction in Biliary Atresia
R01 DK 06400802/25/08-01/31/13$208,271

Bucuvalas, J

Medication Adherence in Children Who Had Liver Transplant
R01 DK 08074012/22/09-06/30/14$59,348
Immunosuppression Withdrawal for Stable Pediatric Liver
U34 DK 08303109/30/09-08/31/11$44,132
Calcineurin Inhibitor Minimization and FOXP3+ Tregs Post Transplant
RC1 DK 08727009/30/09-07/31/11$83,323
Functional Outcomes In Peds Liver Transplantation-Per patient
R01 HD 04569404/01/05-06/30/11$577

Cohen, M

Phase I Study ETEC DMLT
NO1 AI 4001407/19/10-02/16/13$554,427

Cohen, M/Denson, L

Pediatric Gastroenterology and Nutrition Training Grant
T32 DK 00772707/01/10-06/30/15$401,858

Cohen, M/Steinbrecher, K

Expression and Function of the Guanylin Ligand Family
R56 DK 04731808/01/10-07/31/11$250,000

Denson, L

Risk Stratification and Identification of Immunogenetic and Microbial Markers of Complicated Disease Course in Pediatric Crohn's Disease
S30581507/01/09-06/30/13$114,799
Complicated Disease Course in Pediatric Crohn's Disease
S305815 07/01/09-06/30/13$46,308
Biomarkers for Inflammatory Bowel Disease Behavior and Treatment Response
R01 DK07868304/01/09-03/31/13$362,674

Heubi, J

Intervention to Reduce Body Burden of PCBs in Residents
R21 ES 01920608/01/10-07/31/12$67,350
A Model to Predict Outcome of Liver Disease in Alagille Syndrome
07/01/10-06/30/11$6,039
Sterol and Isoprenoid Diseases Rare Diseases Consor
U54 HD06193909/29/09-07/31/14$179,566

Kohli, R

Role of Ileum in Reducing Obesity Related Comorbidities
K08 DK 08431009/01/09-08/31/13$139,300
Ethicon Enhanced Assay Development
07/01/10-06/30/11$73,150

Leonis, M

The Ron Receptor Tyrosine Kinase In Hepatic Tumorigenesis
K08 CA 11181908/01/06-07/31/11$123,000

Miethke, A

Regulatory T cells and the Pathogenesis of Biliary Atresia
07/01/09-06/30/12$75,000

Palermo, J

Bacterial Survival in the Mammalian Urothelium
K08 DK 06835909/01/10-06/30/12$108,438

Samson, C

Granulocyte-Macrophage Colony Stimulating Factor and Homeostatic Responses to Gut Injury
07/01/09-06/30/11$40,000

Shroyer, N

SPDEF in Intestinal Differentiation
R03 DK 08416707/15/09-06/30/11$49,500
The Role of ATOH1 as a Tumor Suppressor in Colorectal Cancer
R01 CA 14282602/23/10-01/31/15$201,001
Cystic Fibrosis Foundation Research Development Program (Project 2)
07/01/07-06/30/11$80,000

Xanthakos, S

Bio Determinants of Steatohepatitis after Adolescent Bariatric Surgery
K23 DK 08088807/01/08-06/30/13$164,300
CRN in Non-Alcoholic Steatohepatitis (NASH CRN)
U01 DK 06173208/30/09-04/30/14$75,673

Yazigi, N

Development & Validation of a Health-Related Quality of Life Questionnaire for Children After Liver Transplantation
04/01/07-06/30/11$14,416
Current Year Direct$5,093,117
Industry Contracts

Saeed, S.

$385

Heubi, J.

$83,763

Kaul, A.

$16,863

Samson, C.

$173
Current Year Direct Receipts$101,184
Total$5,194,301
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