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Mitchell B. Cohen, MD Vice-Chair of Pediatrics for Clinical Affairs
Vice-Chair of Pediatrics for Clinical Affairs
Director, Division of Gastroenterology, Hepatology & Nutrition
Professor, UC Department of Pediatrics
Professor, Associate Professor, Internal Medicine
Diarrheal disorders; inflammatory bowel disease; celiac disease
Intestinal secretion; diarrheal disease; developmental biology
Visit the Cohen-Steinbrecher Lab.
MD: Mount Sinai School of Medicine, New York, NY, 1977.
Residency: Johns Hopkins Hospital, Baltimore, MD, 1977 to 1980.
Fellowship: Pediatric Gastroenterology and Nutrition, Children's Hospital Medical Center of Cincinnati, 1983 to 1986; Research Scholar, Pediatric Gastroenterology and Nutrition, Children's Hospital Medical Center of Cincinnati, 1986 to 1987.
Certification: Pediatrics, 1981; Pediatric Gastroenterology and Nutrition, 1990, 1997, 2004.
Steinbrecher KA, Cohen MB. Transmembrane guanylate cyclase in intestinal pathophysiology. Curr Opin Gastroenterol. 2010 Nov 20. Mann EA, Shanmukhappa K, Cohen MB. Lack of guanylate cyclase C results in increased mortality in mice following liver injury. BMC Gastroenterol. 2010 Aug 2;10:86. Graham RC, Heubi JE, Cohen MB, Li B. Teaching and tomorrow: a novel recruitment program for a pediatric subspecialty. J Pediatr Gastroenterol Nutr. 2009 Nov;49(5):594-8. Cohen MB. Clostridium difficile infections: emerging epidemiology and new treatments. J Pediatr Gastroenterol Nutr. 2009 Apr;48 Suppl 2:S63-5. Garin-Laflam MP, Steinbrecher KA, Rudolph JA, Mao J, Cohen MB. Activation of guanylate cyclase C signaling pathway protects intestinal epithelial cells from acute radiation-induced apoptosis. Am J Physiol Gastrointest Liver Physiol. 2009 Apr;296(4):G740-9. Cohen MB, Gunter JB. How safe is intravenous sedation with midazolam and fentanyl for pediatric gastrointestinal endoscopy? Nat Clin Pract Gastroenterol Hepatol. 2007 Oct;4(10):538-9. Epub 2007 Aug 21.
Pasternak B, Grom A, Yazigi N, Cohen MB. Suppurative peripheral arthritis in inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 2007 Jul;45(1):117-20. No abstract available. Rudolph JA, Pratt J, Mourya R, Steinbrecher KA, Cohen MB. Novel mechanism of cyclic AMP mediated extracellular signal regulated kinase activation in an intestinal cell line. Cell Signal. 2007 Jun;19(6):1221-8. Burrow TA, Cohen MB, Bokulic R, Deutsch G, Choudhary A, Falcone RA Jr, Grabowski GA. Gaucher disease: progressive mesenteric and mediastinal lymphadenopathy despite enzyme therapy. J Pediatr. 2007 Feb;150(2):202-6. Konikoff MR, Noel RJ, Blanchard C, Kirby C, Jameson SC, Buckmeier BK, Akers R, Cohen MB, Collins MH, Assa'ad AH, Aceves SS, Putnam PE, Rothenberg ME. A randomized, double-blind, placebo-controlled trial of fluticasone propionate for pediatric eosinophilic esophagitis. Gastroenterology. 2006 Nov;131(5):1381-91.
Maisam A. Abu-El-Haija, MD Pediatric Gastroenterologist, Division of Pediatric Gastroenterology
is a clinical gastroenterologist who has clinical and translational research interests in pediatric pancreatitis and cystic fibrosis GI related diseases. Her main research focus is on the clinical presentations of pancreatitis, different management trends, and outcomes of pediatric pancreatitis. As part of the pancreatic center at CCHMC, Dr. Abu-El-Haija is working on establishing a database and registry for pediatric pancreatitis. This patient cohort will help determine the epidemiology and potential etiologic factors pancreatitis in children. We hope to study complications and outcomes of therapeutic interventions for pancreatitis, to be able to implement effective therapies with favorable outcomes In the future. Our long term goals are to find effective treatment for pancreatitis.
Pediatric Gastroenterologist, Division of Pediatric Gastroenterology
Assistant Professor, UC Department of Pediatrics
Pediatric gastroenterology; hepatology and nutrition with special focus on pancreatic disease and Cystic Fibrosis.
Our research is essential to study pediatric pancreatitis etiologies, epidemiology, management protocols and outcomes. This disease was thought to be rare in the pediatric population, however recent studies have reported increased incidence to be as close as pancreatitis incidence in the adult patient population. Dr. Abu-El-Haija has the knowledge and motivation necessary to complete the proposed research successfully. Her knowledge in pancreatic disease stemmed from a major interest and then was nourished by her expertise in working with pancreatic disease in a Cystic Fibrosis (CF) Pig Model. This was a basic science lab work.
During Dr. Abu-El-Haija's fellowship training, she dedicated all her research time to conduct research in this Novel Cystic Fibrosis model to look at the pathways involved in pancreatic destruction. She worked with a great group of collaborators in the world of pancreatic disease, CF and pathology and this gave her a great deal of knowledge on how to be able to generate novel data in science. She was successful in getting grants that funded her research in the past. Their work has resulted in publications in peer-reviewed journals and hopefully will help advance the care of our patients.
MBBS: Jordan University of Science and Technology (JUST), Jordan, 1997.
Residency: Pediatrics, University of Iowa Hospitals and Clinics, Iowa City, IA, 2009.
Fellowship: Pediatric Gastroenterology, University of Iowa Hospitals and Clinics, Iowa City, IA, 2012.
Abu-El-Haija M, Stasheff S, Atkins DL, Bishop WP. Rheumatic fever in a patient receiving Infliximab therapy for Crohn disease. J Pediatr Gastroenterol Nutr. 2011 Mar;52(3):360-1.
Abu-El-Haija M, Sinkora M, Meyerholz DK, Welsh MJ, McCray PB Jr, Butler J, Uc A. An Activated Immune and Inflammatory Response Targets the Pancreas of Newborn Pigs with Cystic Fibrosis. Pancreatology. 2011 Nov 1;11(5):506-515.
Sánchez-Vargas FM, Abu-El-Haija MA, Gómez-Duarte OG. Salmonella Infections: An Update on Epidemiology, Management, and Prevention. Travel Med Infect Dis. 2011 Nov;9(6):263-77.
Griffin M*, Abu-El-Haija M*, Abu-El-Haija M, Rokhlina T, Uc, A. A Simplified and Versatile Method for Obtaining High Quality RNA From Pancreas. Biotechniques. 2012 May;52(5):332-4. (* contributed equally)
Abu-El-Haija Maisam, Ramachandran Shyam, Meyerholz David, Abu-El-Haija Marwa, Griffin Michelle, Giriyappa Rhadhamma, Welsh Micheal, McCray Paul, Uc Aliye. Pancreatic Damage in a Cystic Fibrosis Pig Model Involves the Activation of Proinflammatory Pathways. Am J Pathol. 2012 Aug;181(2):499-507.
Abu-El-Haija Maisam, Rahhal Riad, Ebach Dawn. Esophageal Squamous Papilloma in a Pediatric Patient. J Gastroint Dig Syst. 2012;2:3.
Aliye Uc, Radhamma Giriyappa, David K. Meyerholz, Michelle Griffin, Marwa Abu-El-Haija, David A. Stoltz, Paula Ludwig, Alejandro Pezzulo, Maisam Abu-El-Haija, Peter Taft, Michael J. Welsh. Pancreatic and Biliary Secretions Differ in Cystic Fibrosis and Wild Type Pigs. Am J Physiol Gastrointest Liver Physiol. 2012 Oct;303(8):G961-8.
Abu-El-Haija Maisam, Ebach Dawn. NASPGHAN pediatric gastroenterology board review, sections: Stomach: anatomy, physiology, pathology. October 2010.
Abu-El-Haija, Maisam, Ebach, Dawn. NASPGHAN pediatric gastroenterology board review, sections Food poisoning and enteric infections. October 2010.
William F. Balistreri, MD Medical Director, Pediatric Liver Care Center
investigates therapeutic options for children with chronic viral hepatitis B (HBV) and C (HCV). His two multicenter studies include assessing the safety and efficacy of PEG-2a Interferon (IFN) combined with ribavirin (compared to PEG-2a IFN alone) in the treatment of children with chronic hepatitis C and examining the safety and efficacy of Adefovir vs. placebo in inducing clearance of HBV (loss of HBeAg) in chronically infected children.
Medical Director, Pediatric Liver Care Center
Associate Chair for Subspecialty Training, Department of Pediatrics
Liver disease (cholestasis, hepatitis, metabolic liver disease); inflammatory bowel disease
William F. Balistreri, MD, medical director, Pediatric Liver Care Center and associate chair for Subspecialty Training, Department of Pediatrics at Cincinnati Children's Hospital Medical Center, received the 2001 Outstanding Pediatrician award from the Ohio Chapter of the American Academy of Pediatrics. The award is given annually to a pediatrician who is a member of the Ohio Chapter of the AAP for distinguished achievements in pediatric care and in the education of patients and physicians.
"I believe that this award reflects the respect of our colleagues for the entire Cincinnati Children's Hospital Medical Center community rather than any one individual," says Balistreri. "Nevertheless, I am honored to be singled out among all of the outstanding pediatricians in the state of Ohio."
Balistreri is one of the world's foremost authorities on pediatric gastroenterology and liver disease. He is medical director of Cincinnati Children's Pediatric Liver Care Center and Pediatric Liver Transplantation Program.
Through more than 440 publications, including original articles, editorials, reviews and book chapters, Balistreri has helped to clarify the understanding of many aspects of pediatric hepatology -- the branch of medicine concerned with the liver and its diseases. These include bile acid metabolism, neonatal cholestasis (stoppage or suppression of the flow of bile), hepatitis and liver transplantation.
Balistreri has been editor of The Journal of Pediatrics since 1995. He is the former editor-in-chief of the Journal of Pediatric Gastroenterology and Nutrition, and co-editor, associate editor, guest editor, reviewer and member of numerous editorial boards of several journals and periodicals. These include seminars in Liver Disease, Hepatology, Gastroenterology, and the New England Journal of Medicine. He is co-editor of the prestigious text Liver Disease in Children.
In 2000, Balistreri became the first pediatrician to serve as president of the American Association for the Study of Liver Diseases. He is or has been president or a member of numerous prestigious scholarly societies, including the North American Society for Pediatric Gastroenterology and Nutrition.
Balistreri has also served as a member of the board of directors of the American Board of Pediatrics, American Liver Foundation, Institute for Pediatric Medical Education, and the Society for Pediatric Research.
Balistreri has received awards from various societies. These include the Distinguished Leadership Award from the Crohn's and Colitis Foundation of America in 1995, the Andrew Sass-Kortsak Memorial Award from the Canadian Liver Foundation and the Canadian Association for the Study of Liver in 1998, the Murray Davidson Award from the American Academy of Pediatrics Section on Gastroenterology and Nutrition in 1999, and the prestigious Shwachman Award for 1999 from the North American Society for Pediatric Gastroenterology and Nutrition.
Balistreri earned a medical degree at the University of Buffalo School of Medicine in 1970. He was a pediatric resident at Cincinnati Children's from 1971 to 1972 and a post-doctoral fellow from 1972 to 1974. He did a research fellowship in the division of Gastroenterology at the Mayo Foundation, Mayo Clinic, before being appointed assistant professor of pediatrics at the University of Pennsylvania School of Medicine in 1976.
Balistreri joined Cincinnati Children's in 1978, when he also was named associate professor of pediatrics at the University of Cincinnati College of Medicine. In 1984, Balistreri was named Dorothy M. Kersten Professor of Pediatrics at Cincinnati Children's. In 1991, he was appointed professor of medicine at the University of Cincinnati College of Medicine. Balistreri has been listed multiple times in Best Doctors in America.
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 Sep;52(3):934-44.
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 Sep;299(3):G652-60.
Kohli R, Boyd T, Lake K, Dietrich K, Nicholas L, Balistreri WF, Ebach D, Shashidhar H, Xanthakos SA. Rapid progression of NASH in childhood. J Pediatr Gastroenterol Nutr. 2010 Apr;50(4):453-6. Moyer K, Balistreri W. Hepatobiliary disease in patients with cystic fibrosis. Curr Opin Gastroenterol. 2009 May;25(3):272-8.
Leonis MA, Balistreri WF. Evaluation and management of end-stage liver disease in children. Gastroenterology. 2008 May;134(6):1741-51.
Ryckman FC, Bucuvalas JC, Nathan J, Alonso M, Tiao G, Balistreri WF. Outcomes following liver transplantation. Semin Pediatr Surg. 2008 May;17(2):123-30.
Campbell KM, Arya G, Ryckman FC, Alonso M, Tiao G, Balistreri WF, Bezerra JA. High prevalence of alpha-1-antitrypsin heterozygosity in children with chronic liver disease. J Pediatr Gastroenterol Nutr. 2007 Jan;44(1):99-103. Campbell KM, Yazigi N, Ryckman FC, Alonso M, Tiao G, Balistreri WF, Atherton H, Bucuvalas JC. High prevalence of renal dysfunction in long-term survivors after pediatric liver transplantation. J Pediatr. 2006 Apr;148(4):475-80.
Balistreri WF, Bezerra JA. Whatever happened to "neonatal hepatitis"? Clin Liver Dis. 2006 Feb;10(1):27-53, v.Ng VL, Balistreri WF. Treatment options for chronic cholestasis in infancy and childhood. Curr Treat Options Gastroenterol. 2005 Oct;8(5):419-30.
Jorge A. Bezerra, MD
Jorge A. Bezerra, MD, joined the Cincinnati Children's Hospital Medical Center Division of Gastroenterology, Hepatology and Nutrition in 1990, when he began his fellowship training in pediatric gastroenterology and nutrition and graduated in 1993.
From 1992-1994, Dr. Bezerra was a research scholar in the Division of Basic Sciences. He was appointed to the division in 1994 as an assistant professor of pediatrics.
Dr. Bezerra completed his residency in pediatrics at the University of Arizona in Tucson, Arizona.
Dr. Bezerra has an active research career with his primary interests in molecular control of liver regeneration, biliary atresia, and genetic basis of intrahepatic cholestasis.
In addition to his research work, Dr. Bezerra is an active clinician for the outpatient GI clinical service and the inpatient liver service.
MD: Federal University Rio Grande Norte, Natal, Brazil, 1984
Residency: University of Arizona, Tuscon, AZ, 1989
Fellowship: Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, 1994
Certification: Pediatrics, Pediatric Gastroenterology, Hepatology and Nutrition
Bezerra JA. Biliary atresia in Brazil: where we are and where we are going. J Pediatr (Rio J). 2010 Nov-Dec;86(6):445-7. Moyer K, Kaimal V, Pacheco C, Mourya R, Xu H, Shivakumar P, Chakraborty R, Rao M, Magee JC, Bove K, Aronow BJ, Jegga AG, Bezerra JA. Staging of biliary atresia at diagnosis by molecular profiling of the liver. Genome Med. 2010 May 13;2(5):33.
Kumar Mohanty S, Ivantes CA, Mourya R, Pacheco C, Bezerra JA. Macrophages are targeted by rotavirus in experimental biliary atresia and induce neutrophil chemotaxis via Mip2/Cxcl2. Pediatr Res. 2010 Jan 6. Shivakumar P, Sabla GE, Whitington P, Chougnet CA, Bezerra JA. Neonatal NK cells target the mouse duct epithelium via Nkg2d and drive tissue-specific injury in experimental biliary atresia. J Clin Invest. 2009 Aug;119(8):2281-90. Shanmukhappa K, Matte U, Degen JL, Bezerra JA. Plasmin-mediated proteolysis is required for hepatocyte growth factor activation during liver repair. J Biol Chem. 2009 May 8;284(19):12917-23. Erickson N, Mohanty SK, Shivakumar P, Sabla G, Chakraborty R, Bezerra JA. Temporal-spatial activation of apoptosis and epithelial injury in murine experimental biliary atresia. Hepatology. 2008 May;47(5):1567-77. Shivakumar P, Sabla G, Mohanty S, McNeal M, Ward R, Stringer K, Caldwell C, Chougnet C, Bezerra JA. Effector role of neonatal hepatic CD8+ lymphocytes in epithelial injury and autoimmunity in experimental biliary atresia. Gastroenterology. 2007 Jul;133(1):268-77. Liu C, Aronow BJ, Jegga AG, Wang N, Miethke A, Mourya R, Bezerra JA. Novel resequencing chip customized to diagnose mutations in patients with inherited syndromes of intrahepatic cholestasis. Gastroenterology. 2007 Jan;132(1):119-26. Campbell KM, Arya G, Ryckman FC, Alonso M, Tiao G, Balistreri WF, Bezerra JA. High prevalence of alpha-1-antitrypsin heterozygosity in children with chronic liver disease. J Pediatr Gastroenterol Nutr. 2007 Jan;44(1):99-103. Shanmukhappa K, Sabla GE, Degen JL, Bezerra JA. Urokinase-type plasminogen activator supports liver repair independent of its cellular receptor. BMC Gastroenterol. 2006 Nov 29;6:40.
John C. Bucuvalas, MD Associate Medical Director, Pediatric Liver Care Center
has focused his research on improving outcomes for pediatric liver transplant recipients. He is currently working to determine if regulatory cell DNA patterns predict suppressor activity, to conduct an immunosuppression withdrawal trial of transplant recipients, to define an objective marker of non-adherence in transplant recipients and to identify a subgroup of who will respond to immunomodulatory therapy and avoid liver transplantation.
Visit the Bucuvalas Lab.
Associate Medical Director, Pediatric Liver Care Center
Liver disease; transplantation; outcomes research; improving the quality of health care delivery.
John Bucuvalas, MD, came to Cincinnati Children's Hospital Medical Center in 1982 as a fellow in gastroenterology. He joined the faculty in 1986. He graduated from Harvard College in 1974 and Harvard Medical School in 1978. He completed a pediatric residency at Massachusetts General Hospital and served there as chief resident from 1981 to 1982.
Over the last 10 years, the focus his patient care and research efforts have been outcomes research and improving the care delivery system for children with chronic liver disease who then may undergo liver transplantation. He has focused on integration of research into patient care and improving the care delivery system. Along the way, he has gained significant content knowledge through traditional research but additionally have learned how to improve processes, understand the system that is academic medicine, interpret variation and recognize the role of leadership both for research and clinical efforts. Dr. Bucuvalas has made significant contributions in the clinical and research arenas towards improving care, enhancing the delivery care and optimizing the outcome of children with chronic liver disease and pediatric liver transplant recipients.
Dr. Bucuvalas has been recognized as a leader in the field of pediatric hepatology and liver transplantation at a local, regional and national level.
AB: Harvard College, Cambridge, MA, 1974.
MD: Harvard Medical School, Boston, MA, 1978.
Residency: Pediatrics, Massachusetts General Hospital, Boston, MA, 1978 to 1981.
Chief Residency: Pediatrics, Massachusetts General Hospital, Boston, MA, 1981 to 1982.
Fellowship: Gastroenterology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 1982 to 85.
Research Scholar: Gastroenterology, Children's Hospital Research Foundation, Cincinnati, OH, 1985 to 86.
Certification: Pediatrics, 1983; Pediatric Gastroenterology, 1990; recertified, 1997, 2004.
Kathleen M. Campbell, MD
is interested in the care of patients both before and long after pediatric liver transplantation, with a particular interest in risk factors for, and prevention of, chronic renal dysfunction following transplantation.
Associate Professor, UC Department of Pediatrics
Diagnosis and management of pediatric liver disease, particularly biliary atresia and other forms of neonatal cholestasis; liver transplantation and post-transplant renal dysfunction.
Clinical and genetic determinants of calcineurin inhibitor induced post-transplant nephrotoxicity; disease modifiers in biliary atresia
Kathleen M. Campbell, MD, joined the Division of Gastroenterology, Hepatology and Nutrition as a fellow in 2000, after completing her pediatric residency training at Cincinnati Children's Hospital Medical Center. Following the completion of her fellowship, she pursued an additional year of training in Pediatric Hepatology under the mentoring of Dr. William Balistreri and the physicians and surgeons of the Pediatric Liver Care Center, becoming one of the first in her specialty to obtain focused training in this field.
In 2004, Dr. Campbell was appointed assistant professor of pediatrics in the Division of Gastroenterology, Hepatology and Nutrition and the Pediatric Liver Care Center. Her clinical and translational research interests include post-transplant renal dysfunction and genetic modifiers of disease in biliary atresia.
MD: University of Tennessee College of Medicine, Memphis, TN, 1997.
Residency: Pediatrics, University of Cincinnati and Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 2000.
Fellowship: Pediatric Gastroenterology, Hepatology and Nutrition, University of Cincinnati and Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 2003.
Advanced Fellowship: Pediatric Hepatology, University of Cincinnati and Cincinnati Children's Hospital Medical Center, 2004.
Certification: Pediatrics, 2000; Pediatric Gastroenterology, Hepatology and Nutrition, 2003.
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 Oct;15(5):608-13. Choquette M, Goebel JW, Campbell KM. Nonimmune complications after transplantation. Pediatr Clin North Am. 2010 Apr;57(2):505-21, table of contents. Review. Pacheco MC, Campbell KM, Bove KE. Ductal plate malformation-like arrays in early explants after a Kasai procedure are independent of splenic malformation complex (heterotaxy). Pediatr Dev Pathol. 2009 Sep-Oct;12(5):355-60. Calvo-Garcia MA, Campbell KM, O'Hara SM, Khoury P, Mitsnefes MM, Strife CF. Acquired renal cysts after pediatric liver transplantation: association with cyclosporine and renal dysfunction. Pediatr Transplant. 2008 Sep;12(6):666-71. Epub 2008 Mar 6. Campbell KM, Arya G, Ryckman FC, Alonso M, Tiao G, Balistreri WF, Bezerra JA. High prevalence of alpha-1-antitrypsin heterozygosity in children with chronic liver disease. J Pediatr Gastroenterol Nutr. 2007 Jan;44(1):99-103. Bucuvalas JC, Campbell KM, Cole CR, Guthery SL. Outcomes after liver transplantation: keep the end in mind. J Pediatr Gastroenterol Nutr. 2006 Jul;43 Suppl 1:S41-8. Campbell KM, Yazigi N, Ryckman FC, Alonso M, Tiao G, Balistreri WF, Atherton H, Bucuvalas JC. High prevalence of renal dysfunction in long-term survivors after pediatric liver transplantation. J Pediatr. 2006 Apr;148(4):475-80. Shivakumar P, Campbell KM, Sabla GE, Miethke A, Tiao G, McNeal MM, Ward RL, Bezerra JA. Obstruction of extrahepatic bile ducts by lymphocytes is regulated by IFN-gamma in experimental biliary atresia. J Clin Invest. 2004 Aug;114(3):322-9. Campbell KM, Sabla GE, Bezerra JA. Transcriptional reprogramming in murine liver defines the physiologic consequences of biliary obstruction. J Hepatol. 2004 Jan;40(1):14-23.
Campbell KM and Balistreri WF. Inflammatory Bowel Disease. Comprehensive Pediatrics. 1st edition. 2001.
Conrad R. Cole, MD, MPH, MSc Director, Intestinal Rehabilitation
is interested in intestinal rehabilitation and neonatal nutrition. His research focuses on (1) the prevention of blood stream infections and improving nutritional and developmental outcomes in children with short bowel syndrome and intestinal failure and (2) The epidemiology and prevention of micronutrient malnutrition and its consequences in preschool children especially within minority and low income populations.
Director, Intestinal Rehabilitation
Intestinal failure; short bowel syndrome; growth failure; failure to thrive malabsorption disorders; micronutrient malnutrition
Nutritional and developmental outcomes of infants with intestinal failure and short bowel syndrome; nutritional epidemiology of micronutrient malnutrition in preschool children
Conrad Cole, MD, is an expert in the management of infants with intestinal failure and short bowel syndrome. He is an associate director of the Pediatric Nutrition and Intestinal Care Center in the Division of Gastroenterology, Hepatology and Nutrition. In addition, he is an associate professor of pediatrics at the University of Cincinnati College of Medicine.
Dr. Cole's research interest is in the epidemiology of intestinal failure and it's complications especially in identifying risk factors associated with worsening prognosis. He is also interested in micronutrient malnutrition specifically zinc and iron and how they impact other micronutrients in preschool children especially from low income minority populations.
Prior to joining Cincinnati Children's, Dr. Cole was at Emory University's Schools of Medicine and Public Health. Dr. Cole earned his medical degree from the University of Ibadan, and also completed graduate degrees in public health from Ohio State University and clinical research from Emory University. He received training in nutrition under the mentorship of Fima Lifshitz MD at Maimonides Medical Center and Miami Children's Hospital prior to completing an internship and residency in pediatrics at the Miami Children's Hospital; and a fellowship in pediatric gastroenterology at Cincinnati Children's Hospital Medical Center.
Cole CR, Grant FK, Swaby-Ellis ED, Smith JL, Jacques A, Northrop-Clewes CA, Caldwell KL, Pfeiffer CM, Ziegler TR. Zinc and iron deficiency and their interrelationship in low-income African American and Hispanic children in Atlanta. American Journal of Clinical Nutrition. 2010;91:1027-1034.
Cole CR, Grant FK, Tangpricha V, Swaby-Ellis ED, Smith JL, Jacques A, Chen HP, Schleicher RL, Ziegler TR. 25-hydroxyvitamin D status of healthy low-income minority children in Atlanta. Pediatrics. 2010;125: 633-639.
Cole C, Freitas A, Clifton MS, Durham MM. Hereditary Multiple Intestinal Atresias: two new cases and review of the literature. Journal of Pediatric Surgery. 2010;45:E21-24.
Frem J, Sarson Y. Sternberg T, Cole CR. Copper supplementation in parenteral nutrition of cholestatic infants. Journal of Pediatric Gastroenterology, Hepatology and Nutrition. 2010;50: 650-654.
Cole CR, Frem JC, Schmotzer B, Gewirtz AT, Meddings JB, Gold BD, Ziegler TR. The rate of bloodstream infection is high in infants with short bowel syndrome: Relationship with small bowel bacterial overgrowth, enteral feeding and inflammatory and immune responses. Journal of Pediatrics. 2010;156: 941-947.e1.
Frem, J, Gold B, Shehada B, Cole C. Reflux masquerader: Acute H. pylori infection in infants. Journal of Pediatric Gastroenterology & Nutrition. 2008;46:589-592.
Cole CR, Hansen N, Huggins R, Ziegler TR, Stoll BJ for the NICHD neonatal research network. Very low birth weight preterm infants with surgical short bowel syndrome: incidence, morbidity and mortality and growth outcomes at 18-22 months. Pediatrics. 2008;112:e573-582.
Lee A. Denson, MD Medical Director, Inflammatory Bowel Disease Center
Medical Director, Inflammatory Bowel Disease Center
Inflammatory bowel disease; growth failure; celiac disease
Visit the Denson Lab.
The primary focus of Dr. Lee A. Denson's laboratory is to determine the molecular basis for alterations in growth hormone signaling in inflammatory bowel diseases (IBD).
Normal growth and development are dependent upon the ability of growth hormone to regulate IGF-1 expression. Evidence from studies in children with IBD and mouse models of colitis indicates that inflammatory cytokines which are up regulated in this setting may cause an acquired GH resistance. Consequences may include growth failure, altered body composition and impaired mucosal healing.
We are using complementary experimental and patient-based approaches to investigate regulation of growth hormone signaling in mouse models of colitis and in children with Crohn's disease. These include down regulation of the growth hormone receptor and up regulation of a family of post-receptor inhibitory proteins, the Suppressors of Cytokine Signaling (SOCS). These studies should lead to the development of more effective therapies for children with IBD and other chronic inflammatory conditions.
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 Jan;23(1):95-100.
Gray WN, Denson LA, Baldassano RN, Hommel KA. Disease activity, behavioral dysfunction, and health-related quality of life in adolescents with inflammatory bowel disease. Inflamm Bowel Dis. 2010 Nov 4.
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 Nov;20(9):791-5.
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 Aug;51(2):130-9.
Nylund CM, Denson LA, Noel JM. Bacterial enteritis as a risk factor for childhood intussusception: a retrospective cohort study. J Pediatr. 2010 May;156(5):761-5.
Ingerski LM, Baldassano RN, Denson LA, Hommel KA. Barriers to oral medication adherence for adolescents with inflammatory bowel disease. J Pediatr Psychol. 2010 Jul;35(6):683-91.
Tomer G, Wetzler G, Keddache M, Denson LA. Polymorphisms in the IBD5 locus are associated with Crohn disease in pediatric Ashkenazi Jewish patients. J Pediatr Gastroenterol Nutr. 2009 May;48(5):531-7.
Uchida K, Nakata K, Suzuki T, Luisetti M, Watanabe M, Koch DE, Stevens CA, Beck DC, Denson LA, Carey BC, Keicho N, Krischer JP, Yamada Y, Trapnell BC. Granulocyte/macrophage-colony-stimulating factor autoantibodies and myeloid cell immune functions in healthy subjects. Blood. 2009 Mar 12;113(11):2547-56.
Han X, Uchida K, Jurickova I, Koch D, Willson T, Samson C, Bonkowski E, Trauernicht A, Kim MO, Tomer G, Dubinsky M, Plevy S, Kugathsan S, Trapnell BC, Denson LA. Granulocyte-macrophage colony-stimulating factor autoantibodies in murine ileitis and progressive ileal Crohn's disease. Gastroenterology. 2009 Apr;136(4):1261-71, e1-3.
Denson LA. Growth hormone therapy in children and adolescents: pharmacokinetic/pharmacodynamic considerations and emerging indications. Expert Opin Drug Metab Toxicol. 2008 Dec;4(12):1569-80. Review.
Dana (Chelly) Dykes, MD
is working to improve outcomes and healthcare value using personalized tracking, electronic visits, and e-communication.
Pediatric inflammatory bowel disease
BS: Neuroscience and French, Vanderbilt University, Nashville, TN, 2002.
MD: University of Alabama School of Medicine, Birmingham, AL, 2006.
MS: Clinical and Translational Research, University of Cincinnati, Cincinnati, OH, 2012.
Residency: Pediatrics, Children’s Hospital at UAB, Birmingham, AL, 2009.
Fellowship: Pediatric Gastroenterology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, 2012.
Park KT, Crandall WV, Fridge J, Leibowitz IH, Tsou M, Dykes DM, Hoffenberg EJ, Kappelman MD, Colletti RB. Implementable Strategies and Exploratory Considerations to Reduce Costs Associated with Anti-TNF Therapy in Inflammatory Bowel Disease Inflammatory Bowel Diseases. Inflamm Bowel Dis. 2014 May;20(5):946-51.
Dykes DM, Saeed SA. Imaging for inflammatory bowel disease: the new "sounding board". J Pediatr. 2013 Sep;163(3):625-6.
Dykes DM, Towbin AJ, Bonkowski E, Chalk C, Bezold R, Lake K, Kim MO, Heubi JE, Trapnell BC, Podberesky DJ, Denson LA. Increased Prevalence of Luminal Narrowing and Stricturing Identified by Enterography in Pediatric Crohn Disease Patients with Elevated Granulocyte-Macrophage Colony Stimulating Factor Auto-antibodies. Inflamm Bowel Dis. 2013 Sep;19(10):2146-54.
Michael K. Farrell, MD Chief-of-Staff
is interested in general pediatric gastroenterology problems such as gastroesophageal reflux, chronic abdominal pain, celiac disease and inflammatory bowel disease. He is also interested in all nutritional problems of infants, children and adolescents. A particular interest of Dr. Farrell is providing care as close to their community as possible.
Xiaonan Han, PhD
has a laboratory currently focused on intestinal barrier dysfunction in inflammatory bowel disease (IBD). They have generated intestinal epithelial cell signals transducers and activators of transcription (STAT) 5 deficient mice. Specifically, they are working to identify whether STAT5 signaling in enterocytes protects intestinal epithelial cell (IEC) barrier function in response to gut injury.
Signal transducer and activator of transcription (STAT) in inflammatory bowel disease (IBD); gut barrier dysfunction in IBD; drug development in the therapy of IBD.
Visit the Han Lab web site.
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 Aug;59(8):1066-78.
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 Aug;139(2):530-41.
Han X. Intestinal permeability as a clinical surrogate endpoint in the development of future Crohn's disease therapies. Recent Pat Inflamm Allergy Drug Discov. 2010;4(2):159-76. Review.
Groschwitz KR, Ahrens R, Osterfeld H, Gurish MF, Han X, Abrink M, Finkelman FD, Pejler G, Hogan SP. Mast cells regulate homeostatic intestinal epithelial migration and barrier function by a chymase/Mcpt4-dependent mechanism. Proc Natl Acad Sci U S A. 2009 Dec 29;106(52):22381-6.
Han X, Ren X, Jurickova I, Groschwitz K, Pasternak BA, Xu H, Wilson TA, Hogan SP, Denson LA. Regulation of intestinal barrier function by signal transducer and activator of transcription 5b. Gut. 2009 Jan;58(1):49-58.
Carey R, Jurickova I, Ballard E, Bonkowski E, Han X, Xu H, Denson LA. Activation of an IL-6:STAT3-dependent transcriptome in pediatric-onset inflammatory bowel disease. Inflamm Bowel Dis. 2008 Apr;14(4):446-57.
Han X, Osuntokun B, Benight N, Loesch K, Frank SJ, Denson LA. Signal transducer and activator of transcription 5b promotes mucosal tolerance in pediatric Crohn's disease and murine colitis. Am J Pathol. 2006 Dec;169(6):1999-2013.
Han X, Benight N, Osuntokun B, Loesch K, Frank SJ, Denson LA. Tumour necrosis factor alpha blockade induces an anti-inflammatory growth hormone signalling pathway in experimental colitis. Gut. 2007 Jan;56(1):73-81.
James E. Heubi, MD Director, Clinical Translational Research Center
pursues a variety of patient-oriented projects that relate to liver disease and nutrition. He is investigating the pathogenesis of inborn errors of bile acid metabolism, including peroxisomal disorders, and participates in the Childhood Liver Disease Research and Education Network (ChiLDREN) funded by NIH to study rare cholestatic liver diseases. He is also the co-director of the Center for Clinical and Translational Science and Training.
Director, Clinical Translational Research Center
Co-Director, Center for Clinical and Translational Science and Training
Associate Dean, Clinical and Translational Research
Inflammatory bowel disease; cholestatic liver disease; malabsorption
Cholesterol absorption; cholesterol metabolism; inborn errors of bile acid metabolism; bone metabolism in health and disease; TPN-related cholestasis and its treatment
James E. Heubi, MD, has been a practicing pediatric gastroenterologist since 1979, when he joined the staff at Cincinnati Children's Hospital Medical Center.
Dr. Heubi's practice includes the treatment of all disorders affecting the gastrointestinal tract, liver and biliary tract and pancreas.
Dr. Heubi's areas of practice interests include liver disease and complications related to end-stage liver disease and liver transplantation and the management of patients with "short gut" or compromised gut function requiring prolonged enteral or parenteral nutritional support.
Dr. Heubi is the Director of General Clinical Research Center at Cincinnati Children's and is the associate dean for clinical research, University of Cincinnati College of Medicine.
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 May;56(5):840-2. 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 Sep;299(3):G652-60.
Heubi JE. Child health research and the Clinical Translational Science Awards: where have we been and where are we going? Clin Transl Sci. 2010 Jun;3(3):67-8.
Hommel KA, McGraw KL, Ammerman RT, Heubi JE, Hansen M, Dunlap E, Beidel DC. Psychosocial functioning in children and adolescents with gastrointestinal complaints and disorders. J Clin Psychol Med Settings. 2010 Jun;17(2):159-66.
Setchell KD, Zhao X, Jha P, Heubi JE, Brown NM. The pharmacokinetic behavior of the soy isoflavone metabolite S-(-)equol and its diastereoisomer R-(+)equol in healthy adults determined by using stable-isotope-labeled tracers. Am J Clin Nutr. 2009 Oct;90(4):1029-37.
Wooldridge JL, Heubi JE, Amaro-Galvez R, Boas SR, Blake KV, Nasr SZ, Chatfield B, McColley SA, Woo MS, Hardy KA, Kravitz RM, Straforini C, Anelli M, Lee C. EUR-1008 pancreatic enzyme replacement is safe and effective in patients with cystic fibrosis and pancreatic insufficiency. J Cyst Fibros. 2009 Dec;8(6):405-17.
Graham RC, Heubi JE, Cohen MB, Li B. Teaching and tomorrow: a novel recruitment program for a pediatric subspecialty. J Pediatr Gastroenterol Nutr. 2009 Nov;49(5):594-8.
Burke KT, Horn PS, Tso P, Heubi JE, Woollett LA. Hepatic bile acid metabolism in the neonatal hamster: expansion of the bile acid pool parallels increased Cyp7a1 expression levels. Am J Physiol Gastrointest Liver Physiol. 2009 Jul;297(1):G144-51.
Heubi JE. Pancreatic enzyme-replacement therapy in CF: considerations for the USA. Expert Rev Respir Med. 2008 Oct;2(5):589-96.
Heubi JE, Setchell KD, Bove KE. Inborn errors of bile acid metabolism. Semin Liver Dis. 2007 Aug;27(3):282-94.
Stacey S. Huppert, PhD
investigates the cellular contribution and molecular factors required for assembly of the three-dimensional hepatic architecture, during liver development, homeostasis and regeneration. Defining the critical elements involved in formation and repair processes of the liver are necessary not only to understand biology, but also to identify the cellular and molecular targets involved in congenital and chronic liver diseases.
Visit the Huppert Lab
Hepatic development and regeneration; three-dimensional hepatic architecture; Notch signaling; hepatobiliary disease
Visit the Huppert Lab.
BS: Genetic Biology,Purdue University, West Lafayette, IN, 1992.
PhD: Genetics, Indiana University, Bloomington, IN, 1998.
Postdoctoral Fellow: Developmental Biology, Washington University School of Medicine, St. Louis, MO, 2003.
Instructor: Developmental Biology, Washington University School of Medicine, St. Louis, MO, 2005.
Assistant Professor: Cell and Developmental Biology, Center for Stem Cell Biology, Vanderbilt University Medical Center, Nashville, TN, 2012.
Chen TW, Broadus MR, Huppert SS, Lee E. Reconstitution Of β-catenin Degradation In Xenopus Egg Extract. J Vis Exp. 2014 Jun 17;(88).
Poling HM, Mohanty SK, Tiao GM, Huppert SS. A comprehensive analysis of aquaporin and secretory related gene expression in neonate and adult cholangiocytes. Gene Expr Patterns. 2014 Jun 12;15(2):96-103.
Walter TJ, Cast AE, Huppert KA, Huppert SS. Epithelial VEGF signaling is required in the mouse liver for proper sinusoid endothelial cell identity and hepatocyte zonation in vivo. Am J Physiol Gastrointest Liver Physiol. 2014 May 15;306(10):G849-62.
Walter TJ, Vanderpool C, Cast AE, Huppert SS. Intrahepatic bile duct regeneration in mice does not require Hnf6 or Notch signaling through Rbpj. Am J Pathol. 2014 May;184(5):1479-88.
Walter TJ, Sparks EE, Huppert SS. 3-dimensional resin casting and imaging of mouse portal vein or intrahepatic bile duct system. J Vis Exp. 2012 Oct 25;(68):e4272.
Hang BI, Thorne CA, Robbins DJ, Huppert SS, Lee LA, Lee E. Screening for small molecule inhibitors of embryonic pathways: sometimes you gotta crack a few eggs. Bioorg Med Chem. 2012 Mar 15;20(6):1869-77.
Humphreys R, Zheng W, Prince LS, Qu X, Brown C, Loomes K, Huppert SS, Baldwin S, Goudy S. Cranial neural crest ablation of Jagged1 recapitulates the craniofacial phenotype of Alagille syndrome patients. Hum Mol Genet. 2012 Mar 15;21(6):1374-83.
Vanderpool C, Sparks EE, Huppert KA, Gannon M, Means AL, Huppert SS. Genetic interactions between hepatocyte nuclear factor-6 and Notch signaling regulate mouse intrahepatic bile duct development in vivo. Hepatology. 2012 Jan;55(1):233-43.
Sparks EE, Perrien DS, Huppert KA, Peterson TE, Huppert SS. Defects in hepatic Notch signaling result in disruption of the communicating intrahepatic bile duct network in mice. Dis Model Mech. 2011 May;4(3):359-67.
Sparks EE, Huppert KA, Brown MA, Washington MK, Huppert SS. Notch signaling regulates formation of the three-dimensional architecture of intrahepatic bile ducts in mice. Hepatology. 2010 Apr;51(4):1391-400.
Ajay Kaul, MD Director, Neurogastroenterology and Motility Disorders
is interested in evaluating gastrointestinal motility disorders especially in children with neurodevelopmental delay. He is currently investigating clinical outcomes after combined endoscopic pyloric Botox injection and balloon dilation in children with gastroparesis and the development of rumination syndrome in this cohort.
Director, Neurogastroenterology and Motility Disorders
Director, Gastrointestinal Operations, Liberty Campus
Motility disorders; feeding disorders; GI problems in children with special needs
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 Jan 12.
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 Jan;127(1):208-17, 217.e1-7.
Garza JM, Kaul A. Gastroesophageal reflux, eosinophilic esophagitis, and foreign body. Pediatr Clin North Am. 2010 Dec;57(6):1331-45. Review.
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 Jul;139(1):182-93.e7.
Caldwell JM, Blanchard C, Collins MH, Putnam PE, Kaul A, Aceves SS, Bouska CA, Rothenberg ME. Glucocorticoid-regulated genes in eosinophilic esophagitis: a role for FKBP51. J Allergy Clin Immunol. 2010 Apr;125(4):879-888.e8.
Blanchard C, Stucke EM, Burwinkel K, Caldwell JM, Collins MH, Ahrens A, Buckmeier BK, Jameson SC, Greenberg A, Kaul A, Franciosi JP, Kushner JP, Martin LJ, Putnam PE, Abonia JP, Wells SI, Rothenberg ME. Coordinate interaction between IL-13 and epithelial differentiation cluster genes in eosinophilic esophagitis. J Immunol. 2010 Apr 1;184(7):4033-41.
Jafri M, Alonso M, Kaul A, Dierig J, Racadio J, Inge T, Brown R, Ryckman F, Tiao G. Intraoperative manometry during laparoscopic Heller myotomy improves outcome in pediatric achalasia. J Pediatr Surg. 2008 Jan;43(1):66-70; discussion 70.
Pentiuk SP, Miller CK, Kaul A. Eosinophilic esophagitis in infants and toddlers. Dysphagia. 2007 Jan;22(1):44-8.
Boesch RP, Daines C, Willging JP, Kaul A, Cohen AP, Wood RE, Amin RS. Advances in the diagnosis and management of chronic pulmonary aspiration in children. Eur Respir J. 2006 Oct;28(4):847-61. Review.
Bates MD, Dunagan DT, Welch LC, Kaul A, Harvey RP. The Hlx homeobox transcription factor is required early in enteric nervous system development. BMC Dev Biol. 2006 Jul 19;6:33.
Samuel A. Kocoshis, MD Medical Director, Intestinal Care Center
is investigating ways to minimize intestinal dysfunction following transplantation and also collaborating to better characterize immunologic factors contributing to graft versus host disease and severe acute cellular rejection in intestinal transplantation. Dr. Kocoshis is also interested in identifying biomarkers that predict the development of parenteral nutrition-associated cholestasis.
Medical Director, Intestinal Care Center
Medical Director, Small Bowel Transplantation Program
Management of complex intestinal and liver disease; small bowel transplantation; general disorders of the gastrointestinal tract
Altered bile acid metabolism in gastrointestinal disease; small bowel transplantation; inflammatory bowel disease; short bowel syndrome
Samuel Kocoshis, MD, is an expert in the management of complex intestinal and liver disease at Cincinnati Children's Hospital Medical Center.
Dr. Kocoshis is the director of the Pediatric Nutrition and Intestinal Care Center in the Pediatric Gastroenterology, Hepatology and Nutrition Division, and is also the medical director of the Small Intestinal Transplantation Program. In addition, he is professor of pediatrics at the University of Cincinnati College of Medicine.
Dr. Kocoshis' long-standing research interest has been altered bile acid metabolism in gastrointestinal disease. His current clinical research program focuses upon intestinal adaptation following massive small intestinal resection, as well as the immunology of intestinal transplantation.
Prior to joining Cincinnati Children's, Dr. Kocoshis was chief of Pediatric Gastroenterology and co-director of the Intestinal Care Center at Children's Hospital of Pittsburgh, and professor of pediatrics at the University of Pittsburgh School of Medicine.
Dr. Kocoshis earned his bachelor's degree from DePauw University and his medical degree from the Medical College of Wisconsin. He completed an internship in pediatrics at the West Virginia University Medical Center; a residency in pediatrics at Children's Hospital of Pittsburgh; and a clinical fellowship in gastroenterology at Yale University School of Medicine.
Kocoshis SA. Medical management of pediatric intestinal failure. Semin Pediatr Surg. 2010 Feb;19(1):20-6. Review.
Wessel JJ, Kocoshis SA. Nutritional management of infants with short bowel syndrome. Semin Perinatol. 2007 Apr;31(2):104-11. Review.
Nathan JD, Rudolph JA, Kocoshis SA, Alonso MH, Ryckman FC, Tiao GM. Isolated liver and multivisceral transplantation for total parenteral nutrition-related end-stage liver disease. J Pediatr Surg. 2007 Jan;42(1):143-7.
Kocoshis S. Small Intestinal Failure in Children. Curr Treat Options Gastroenterol. 2001 Oct;4(5):423-432.
Rohit Kohli, MBBS, MS Associate Medical Director, Liver Transplant Program
is researching the pathogenesis of obesity related fatty liver disease and his laboratory has developed a novel diet-induced murine model to study this disease. He is also working to determine how obesity and fatty liver disease respond to weight loss after bariatric surgery and to understand what role bile acids and bile acid recycling play in the weight-independent benefits of various bariatric procedures.
Visit the Kohli Lab.
Associate Medical Director, Liver Transplant Program
Co-Director, Steatohepatitis Center
Attending Physician, Liver Care Center
Non-alcoholic steatohepatitis; liver transplantation; mitochondrial hepatopathies
Obesity related fatty liver disease (non-alcoholic steatohepatitis)
Visit the Kohli Lab
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 Feb;52(2):190-197.
Kohli R. Indian Childhood Cirrhosis- Revisited. J of Pediatr. 2010 Nov;157:766.
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 Sep;52(3):934-44.
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 Sep;299(3):G652-60.
Kohli R, Boyd T, Lake K, Dietrich K, Nicholas L, Balistreri WF, Ebach D, Shashidhar H, Xanthakos SA. Rapid progression of NASH in childhood. J Pediatr Gastroenterol Nutr. 2010 Apr;50(4):453-6.
Carter-Kent C, Brunt EM, Xanthakos SA, Kohli R, Whitington PF, Angulo P, Feldstein AE. Nonalcoholic steatohepatitis in children: a multicenter clinicopathological study. Hepatology. 2009 Oct; 50(4):1113-20.
Kohli R, Ramsingh H, Makkad B. The anesthetic management of ocular trauma. Int Anesthesiol Clin. 2007 Summer;45(3):83-98. Review.
Kohli R, Pan X, Malladi P, Wainwright MS, Whitington PF. Mitochondrial reactive oxygen species signal hepatocyte steatosis by regulating the PI 3-kinase cell survival pathway. Journal of Biological Chemistry. 2007 Jul 20;282(29):21327-36.
Sahai A, Pan X, Paul R, Malladi P, Kohli R, Whitington PF. Roles of phosphatidylinositol 3-kinase and osteopontin in steatosis and aminotransferase release by hepatocytes treated with methionine-choline deficient medium. American Journal of Physiology. 2006 Jul; 291(1): G55-62.
Kohli R, Alonso EM, Whitington PF. Liver Transplantation: The Recipient: Long-term Outcome: Pediatric Recipient. In Living Donor Organ Transplantation, Gruessner RWG, Benedetti E (Eds). New York: McGraw Hill, 2008.
Role of Ileum in Reducing Obesity Related Comorbidities. Principal Investigator. National Institutes of Health. Sep 2009 - Aug 2013. #1K08DK084310.
Ethicon Enhanced Assay Development. Co-investigator. University of Cincinnati. Jan 2009 - Jan 2014.
Clinical Research Network in Non-Alcoholic Steatohepatitis (NASH CRN). Co-investigator. National Institutes of Health. Aug 2009 - Apr 2014. #U01DK061732.
Mike A. Leonis, MD, PhD
investigates the mechanisms of hepatic tumorigenesis. The long term goal of his research is to define the role of the Ron receptor tyrosine kinase in liver pathophysiology, focusing primarily on the role of Ron gain-of-function in hepatic tumorigenesis. A second research interest involves understanding the clinical characteristics and outcomes of pediatric patients with acute liver failure.
Pediatric hepatology, especially acute liver failure; inflammatory disease processes of the liver; hepatoblastoma; mechanisms of hepatic tumor formation
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 May;53(5):1618-28.
Kenny AP, Crimmins NA, Mackay DJ, Hopkin RJ, Bove KE, Leonis MA. Concurrent course of transient neonatal diabetes with cholestasis and paucity of interlobular bile ducts: a case report. Pediatr Dev Pathol. 2009 Sep-Oct;12(5):417-20.
Caldwell CC, Martignoni A, Leonis MA, Ondiveeran HK, Fox-Robichaud AE, Waltz SE. Ron receptor tyrosine kinase-dependent hepatic neutrophil recruitment and survival benefit in a murine model of bacterial peritonitis. Crit Care Med. 2008 May;36(5):1585-93.
Leonis MA, Thobe MN, Waltz SE. Ron-receptor tyrosine kinase in tumorigenesis and metastasis. Future Oncol. 2007 Aug;3(4):441-8. Review.
Zinser GM, Leonis MA, Toney K, Pathrose P, Thobe M, Kader SA, Peace BE, Beauman SR, Collins MH, Waltz SE. Mammary-specific Ron receptor overexpression induces highly metastatic mammary tumors associated with beta-catenin activation. Cancer Res. 2006 Dec 15;66(24):11967-74.
Wetzel CC, Leonis MA, Dent A, Olson MA, Longmeier AM, Ney PA, Boivin GP, Kader SA, Caldwell CC, Degen SJ, Waltz SE. Short-form Ron receptor is required for normal IFN-gamma production in concanavalin A-induced acute liver injury. Am J Physiol Gastrointest Liver Physiol. 2007 Jan;292(1):G253-61.
Leonis MA, Toney-Earley K, Degen SJ, Waltz SE. Deletion of the Ron receptor tyrosine kinase domain in mice provides protection from endotoxin-induced acute liver failure. Hepatology. 2002 Nov;36(5):1053-60.
Alexander G. Miethke, MD
is interested in susceptibility factors for neonatal liver injury, including biliary atresia. He focuses on the interaction between the maturing adaptive immune system and hepatic immune responses to infectious insults during the early neonatal period.
Pediatric liver disease including biliary atresia, inherited liver diseases, autoimmune hepatitis, and primary sclerosing cholangitis; gastrointestinal problems in children with bone marrow failure syndromes
Immune mediated liver injury, specifically the role of regulatory T cells in biliary atresia and primary sclerosing cholangitis; genetic basis for intrahepatic cholestasis in children; acute liver failure in infants with mitochondrial disorders
MD: Humboldt-University, Berlin, Germany, 2000.Residency: Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 2002-2004.Fellowship: Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 2005-2007.
Advanced Fellowship: Pediatric Transplant Hepatology, University of Cincinnati and Cincinnati Children's Hospital Medical Center, 2009.Certification: Pediatrics, 2005; Pediatric Gastroenterology 2009; Pediatric Transplant Hepatology, 2010.
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.
Miethke AG, Saxena V, Shivakumar P, Sabla GE, Simmons J, Chougnet CA. Post-natal paucity of regulatory T cells and control of NK cell activation in experimental biliary atresia. J Hepatol. 2010 May;52(5):718-26.
Liu C, Aronow BJ, Jegga AG, Wang N, Miethke A, Mourya R, Bezerra JA. Novel resequencing chip customized to diagnose mutations in patients with inherited syndromes of intrahepatic cholestasis. Gastroenterology. 2007 Jan;132(1):119-26.
Shivakumar P, Campbell KM, Sabla GE, Miethke A, Tiao G, McNeal MM, Ward RL, Bezerra JA. Obstruction of extrahepatic bile ducts by lymphocytes is regulated by IFN-gamma in experimental biliary atresia. J Clin Invest. 2004 Aug;114(3):322-9.
Sean R. Moore, MS, MD
is interested in the vicious cycle of childhood diarrhea and malnutrition in developing countries, with a current focus on the mechanisms of a promising glutamine-based oral rehydration and nutrition therapy. Dr. Moore studies the signaling pathways by which alanyl-glutamine promotes gut homeostasis and also collaborates with colleagues on the epidemiology and impact of early childhood diarrhea and undernutrition in impoverished settings.
General gastroenterology; inflammatory bowel diseases
Diarrheal diseases; glutamine; global health
Moore SR. Update on prolonged and persistent diarrhea in children. Curr Opin Gastroenterol. 2010 Sep 10.
Moore SR, Lima NL, 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. 2010 Oct;139(4):1156-64.
Guerrant RL, Oriá RB, Moore SR, Oriá MOB, Lima AA. Malnutrition as an enteric infectious disease, with long-term effects on child development. Nutr Rev. 2008;66(9):487-505.Checkley W, Buckley G, Gilman RH, Assis AM, Guerrant RL, Morris SS, Mølbak K, Valentiner-Branth P, Lanata CF, Black RE. Multi-country analysis of the effects of diarrhoea on childhood stunting. Int J Epidemiol. 2008;37(4):816-30. Moore SR, Lorntz B, Lima AA, Guerrant RL. Risk factors for adverse outcomes in developing countries. Lancet. 2007;369(9564):824-5.
Joseph J. Palermo, MD, PhD
is interested in focusing on disorders of the bile ducts. He has developed an animal model to investigate the causes of immune mediated cholangiopathies. Additionally, he is exploring the use of decision analytic modeling to improve outcomes for patients with biliary atresia. Dr. Palermo is also investigating how to utilize state of the art imaging techniques to improve the diagnosis and management of cystic fibrosis liver disease.
General gastroenterology and hepatology
Cholestatic liver disease; biliary atresia; cystic fibrosis liver disease
MD: University of Cincinnati, Cincinnati, OH, 1997.
PhD: University of Cincinnati, Cincinnati, OH, 1997. Residency: Pediatrics, St. Louis Children’s Hopsital and Washington University, St. Louis MO.Fellowship: Pediatric Gastroenterology, Hepatology and Nutrition, Washington University, St. Louis, MO.Certification: Pediatric Gastroenterology, 2001.
Bacterial Survival in the Mammalian Urothelium. Principal Investigator. National Institutes of Health. 2006 - 2011. #K08 DK068359-02.
Longitudinal study of Cystic Fibrosis Liver Disease (PUSH). Site Principal Investigator. National Institutes of Health. 2010 - 2013.
Scott P. Pentiuk, MD Pediatric Gastroenterologist
has clinical interests in feeding disorders and general gastroenterology. He is working on outcomes, quality of life, and the use of pureed by gastrostomy tube feedings in children with feeding disorders. Additionally, Dr Pentiuk has a strong interest in medical education and curriculum design for gastroenterology at the resident and fellowship levels.
Feeding disorders, medical education
MD: University of Cincinnati College of Medicine, Cincinnati, Ohio, 2002.
Residency: Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, 2005.
Fellowship: Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, 2008.
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 May;50(5):521-5.
Pentiuk S, Putnam PE, Collins MH, Rothenberg ME. Dissociation between symptoms and histological severity in pediatric eosinophilic esophagitis. J Pediatr Gastroenterol Nutr. 2009 Feb;48(2):152-60.
Pentiuk SP, Miller CK, Kaul A. Eosinophilic esophagitis in infants and toddlers. Dysphagia. 2007 Jan;22(1):44-8. Epub 2006 Oct 6.
Philip E. Putnam, MD Director, Endoscopy Services
is interested in the clinical diagnosis and treatment of eosinophilic gastrointestinal disorders. He is the medical director of the Cincinnati Center for Eosinophilic Disorders. He is also taking part in the Aerodigestive and Sleep Center, a multidisciplinary group including ENT, pulmonary medicine, and pediatric surgery, which evaluates and treats children who have complex disorders involving the airway and gastrointestinal tracts.
Director, Endoscopy Services
Eosinophilic enteritis; abdominal pain; gastroesophageal reflux; complex nutrition related to the GI tract; GI bleeding; inflammatory bowel disease; diarrhea and failure to thrive
MD: University of Michigan Medical School, Ann Arbor, MI, 1984.
Residency: University of Pittsburgh, Children's Hospital of Pittsburgh, Pittsburgh, PA, 1984-1987.
Fellowship: University of Pittsburgh, Children's Hospital of Pittsburgh, Pittsburgh, PA, 1988-1991.
Certification: Pediatrics, 1988; Pediatric Gastroenterology, 1995.
Michael J. Rosen, MD, MSCI Attending Physician, Division of Gastroenterology, Hepatology and Nutrition
and his laboratory study mechanisms of inflammation in pediatric chronic colitis. 50,000 children in the US suffer from inflammatory bowel disease (IBD), and 25% of patients with IBD are diagnosed as children. Dr. Rosen focuses on the contribution of Type 2 inflammation to chronic colitis. His laboratory pairs patient-based studies with studies animal models to identify molecular mechanisms underpinning chronic inflammation in human IBD.
Attending Physician, Division of Gastroenterology, Hepatology and Nutrition
Physician, Schubert-Martin Inflammatory Bowel Disease Center
Inflammatory bowel disease
Inflammatory bowel disease; intestinal mucosal immunology
Michael J. Rosen, MD, MSCI, focuses his career on the clinical care of children with inflammatory bowel disease (IBD), and to research aimed at better understanding the causes of chronic inflammation in childhood IBD. The primary focus of Dr. Rosen's laboratory is on the contribution of Type 2 (Th2) inflammation to pediatric colitis. Studies from Dr. Rosen’s lab have demonstrated increased mucosal activation of STAT6, a key Th2 cellular signaling protein, in children with ulcerative colitis and shown a role for STAT6 in perpetuating inflammation in a mouse model similar to ulcerative colitis.
Dr. Rosen is currently funded by the National Institutes of Health (NIH) to study the expression of genes related to Th2 inflammation in colon tissue form a large cohort of children with IBD. In addition, his laboratory is conducting ongoing studies with transgenic animal models to determine the mechanisms by which proteins important in perpetuating Th2 inflammatory responses contribute to inflammation in colitis.
Dr. Rosen serves on the National Pediatric Affairs Committee for the Crohn's & Colitis Foundation of America (CCFA). His a past recipient of the Fellow to Faculty Transition Award in IBD and the George Ferry Young Investigator Award from the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN).
MD: Harvard Medical School, Boston, MA, 2003.
Residency: Boston Combined Residency Program in Pediatrics (Boston Children's Hospital and Boston Medical Center), Boston, MA, 2003-2006.
Fellowship: Pediatric Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center and the Monroe Carell, Jr. Children's Hospital at Vanderbilt, Nashville, TN 2006-2009.
Masters of Science in Clinical Investigation (MSCI): Vanderbilt University School of Medicine, Nashville, TN, 2009.
Certification: Pediatrics, 2007; Pediatric Gastroenterology, Hepatology and Nutrition, 2009.
Lu N, Lieu L, Van Kaer L, Washington MK, Rosen MJ, Dubé P, Wilson KT, Ren X, Hao X Polk DB, Yan F. Activation of the EGFR in macrophages regulates cytokine production and experimental colitis. The Journal of Immunology. 2014; 192(3):1013-23.
Falaiye TO, Mitchell KR, Lu Z, Saville BR, Horst SN, Moulton DE, Schwartz DA, Wilson KT, Rosen MJ. Outcome following infliximab therapy for pediatric patients hospitalized with refractory colitis-predominant inflammatory bowel disease. Journal of Pediatric Gastroenterology and Nutrition. 2014; 58(2):213-9.
Rosen MJ*, Chaturvedi R, Washington MK, Kuhnhein LA, Moore PD, Coggeshall SS, McDonough EM, Weitkamp JH, Singh AB. Coburn LA, Williams CS, Van Kaer L, Peebles RS, Wilson KT. STAT6 activation intensifies disease severity while increasing expression of claudin-2 and Th2-inducing cytokines in murine oxazolone colitis. The Journal of Immunology. 2013; 190(4):1849-1858.
Weitkamp JH, Koyama T, Rock MT, Correa H, Goettel J Matta P, Oswald-Richter K, Rosen MJ, Engelhardt BG, Moore D, Polk DB. Diminished mucosal regulatory (FOXP3+) / effector (CD4+, CD8+) T cell ratios as evidence for disrupted immune regulation in necrotizing enterocolitis. Gut. 2013; 62(1):73-82.
Rosen MJ, Denson LA, Kugathasan S. Commentaries on "Workshop report: developing a pediatric inflammatory bowel diseases network and data platform in Canada": pediatric inflammatory bowel disease networks: raising the bar. Journal of Pediatric Gastroenterology and Nutrition. 2012 Aug;55(2):121-2.
Rosen MJ*, Frey MR, Washington MK, Chaturvedi R, Kuhnhein LA, Matta P, Revetta F, Wilson KT, Polk DB. STAT6 activation in ulcerative colitis: A new target for prevention of IL-13-induced colonic epithelial cell dysfunction. Inflammatory Bowel Diseases. 2011; 17(11):2224-2234.
Rosen MJ, Schwartz DA. 31 Year-old with Colitis and Perianal Disease. Clinical Gastroenterology and Hepatology. 2010;8(1):10-4.
Rosen MJ, Moulton DE, Koyama T, Morgan WM, Morrow SE, Herline AJ, Muldoon RL, Wise PE, Polk DB, Schwartz DA. Endoscopic Ultrasound to Guide the Combined Medical and Surgical Management of Pediatric Perianal Crohn’s Disease. Inflammatory Bowel Diseases. 2010; 16(3):461-8.
Forcione DG, Rosen MJ, Kisiel JB, Sands BE. Anti-Saccharomyces cerevisiae antibody (ASCA) positivity is associated with increased risk for early surgery in Crohn's disease. Gut. 2004;53:1117-1122.
Sands BE, Arsenault JE, Rosen MJ, et al. Risk of Early Surgery for Crohn's Disease: Implications for Early Treatment Strategies. American Journal of Gastroenterology. 2003;98(12):2712-2718.
Th2 Cytokines and Signaling in Pediatric Inflammatory Bowel Disease. Principal Investigator. National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (NIH/NIDDK). Mar 2013-Mar 2018.
Myeloid Cell-Derived IL-33 in Chronic IL-10-Deficient Colitis. Principal Investigator. Cincinnati Children's Research Foundation. Jul 2014-Jun 2016.
Shehzad Ahmed Saeed, MD, FAAP, AGAF Clinical Director, Schubert–Martin Inflammatory Bowel Disease Center
is interested in the epidemiology of pediatric inflammatory bowel disease (IBD). Specifically, he studies the genetic and phenotypic correlations as well as risk stratification for surgery in children with IBD. Additionally, Dr. Saeed will focus on outcomes of patients with IBD.
Clinical Director, Schubert–Martin Inflammatory Bowel Disease Center
Clinical Director, Division of Gastroenterology, Hepatology and Nutrition
Medical Director, Gi/Colorectal Inpatient Unit
Inflammatory bowel disease
Quality improvement in inflammatory bowel disease
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 Jan;36(1):64-73.
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 Sep;8(9):789-94.
Malik TA, Saeed S. Autoimmune hepatitis: a review. J Pak Med Assoc. 2010 May;60(5):381-7. Wallander JL, Madan-Swain A, Klapow J, Saeed S. A randomised controlled trial of written self-disclosure for functional recurrent abdominal pain in youth. Psychol Health. 2010 Apr 21:1-15.
Imielinski M, Baldassano RN, Griffiths A, et.al. Common variants at five new loci associated with early-onset inflammatory bowel disease. Nat Genet. 2009 Dec;41(12):1335-40.
Colletti RB, Baldassano RN, Milov DE, Margolis PA, Bousvaros A, Crandall WV, Crissinger KD, D'Amico MA, Day AS, Denson LA, Dubinsky M, Ebach DR, Hoffenberg EJ, Kader HA, Keljo DJ, Leibowitz IH, Mamula P, Pfefferkorn MD, Qureshi MA; Pediatric IBD Network for Research and Improvement. Variation in care in pediatric Crohn disease. J Pediatr Gastroenterol Nutr. 2009 Sep;49(3):297-303. Maheshwari A, Kurundkar AR, Shaik SS, Kelly DR, Hartman Y, Zhang W, Dimmitt R, Saeed S, Randolph DA, Aprahamian C, Datta G, Ohls RK. Epithelial cells in fetal intestine produce chemerin to recruit macrophages. Am J Physiol Gastrointest Liver Physiol. 2009 Jul;297(1):G1-G10. Donnithorne KJ, Atkinson TP, Hinze CH, Nogueira JB, Saeed SA, Askenazi DJ, Beukelman T, Cron RQ. Rituximab therapy for severe refractory chronic Henoch-Schönlein purpura. J Pediatr. 2009 Jul;155(1):136-9. Haricharan RN, Proklova LV, Aprahamian CJ, Morgan TL, Harmon CM, Barnhart DC, Saeed SA. Laparoscopic cholecystectomy for biliary dyskinesia in children provides durable symptom relief. J Pediatr Surg. 2008 Jun;43(6):1060-4. Britton LJ, Saeed SA. Abdominal pain in cystic fibrosis. J Pediatr Health Care. 2008 Nov-Dec;22(6):383-6.
Pranavkumar Shivakumar, PhD
Instructor, UC Department of Pediatrics
PhD: University of Bombay, Bombay, India, 2002.
MPharm: University of Bombay, Bombay, India, 1997.
Shivakumar P, Shanmugam RP, Mani CS. Idiopathic granulomatous appendicitis: a rare appendicular pseudo tumor. Trop Gastroenterol. 2010 Apr-Jun;31(2):130-1.
Moyer K, Kaimal V, Pacheco C, Mourya R, Xu H, Shivakumar P, Chakraborty R, Rao M, Magee JC, Bove K, Aronow BJ, Jegga AG, Bezerra JA. Staging of biliary atresia at diagnosis by molecular profiling of the liver. Genome Med. 2010 May 13;2(5):33.
Miethke AG, Saxena V, Shivakumar P, Sabla GE, Simmons J, Chougnet CA. Post-natal paucity of regulatory T cells and control of NK cell activation in experimental biliary atresia. J Hepatol. 2010;52(5):718-26.
Shivakumar P, Krauthammer M. Structural similarity assessment for drug sensitivity prediction in cancer. BMC Bioinformatics. 2009 Sep 17;10 Suppl 9:S17.
Shivakumar P, Sabla G, Whitington P, Chougnet C, Bezerra JA. Neonatal NK cells target the mouse duct epithelium via Nkg2d and drive tissue-specific injury in experimental biliary atresia. J Clin Invest. 2009;119(8):2281-90.Erickson N, Mohanty SK, Shivakumar P, Sabla G, Chakraborty R, Bezerra JA. Temporal-spatial activation of apoptosis and epithelial injury in murine experimental biliary atresia. Hepatology. 2008;47(5):1567-77.
Shivakumar P, Sabla G, Mohanty S, McNeal M, Ward R, Stringer K, Caldwell C, Chougnet C, Bezerra JA. Effector role of neonatal hepatic CD8+ lymphocytes in epithelial injury and autoimmunity in experimental biliary atresia. Gastroenterology. 2007 Jul;133(1):268-77. Shanmugam RP, Shivakumar P. A rare complication of jejunal diverticulosis. Trop Gastroenterol. 2006 Jul-Sep;27(3):134-5. Mohanty SK, Shivakumar P, Sabla G, Bezerra JA. Loss of interleukin-12 modifies the pro-inflammatory response but does not prevent duct obstruction in experimental biliary atresia. BMC Gastroenterol. 2006 Apr 19;6:14.
Carvalho E, Liu C, Shivakumar P, Sabla G, Aronow B, Bezerra JA. Analysis of the biliary transcriptome in experimental biliary atresia. Gastroenterology. 2005 Aug;129(2):713-7.
Noah F. Shroyer, PhD
is focused on understanding development and diseases of the intestine. He seeks to understand the molecular mechanisms of intestinal epithelial differentiation, and to apply this knowledge to gain insight into major diseases of the intestine such as colon cancer and inflammatory bowel disease.
Visit the Shroyer Lab.
Intestinal epithelial development; colon cancer; inflammatory bowel disease.
BS: Microbiology and Biochemistry, Louisiana State University, Baton Rouge, LA, 1995.
PhD: Cell and Molecular Biology, Baylor College of Medicine, Houston, TX, 2001.
Postdoctoral: Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 2001-2005.
Spence JR, Lauf R, Shroyer NF. Vertebrate intestinal endoderm development. Dev Dyn. 2011 Mar;240(3):501-20.
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 Feb 3;470(7332):105-9.
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 Sep;139(3):918-28, 928.e1-6.
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 Sep;299(3):G652-60. 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 Jul;17(4):300-7.
Noah TK,Kazanjian A, Whitsett J, Shroyer NF. SAM Pointed Domain ETS Factor (SPDEF) regulates terminal differentiation and maturation of intestinal goblet cells. Exp Cell Res. 2010 Feb;316(3):452-65.
Bossuyt W, Kazanjian A, Aerts S, Leenaerts I, Claeys A, de Geest N, van Kelst S, de Hertogh G, Geboes K, Chuah M, Boivin GP, VandenDriessche T, Marynen P, Cools J, Shroyer NF, Hassan BA. Atonal homolog 1 (Atoh1) is a tumor suppressor gene. PLoS Biology. 2009;7:e39. Kiesslich R, Goetz M, Angus EM, Hu Q, Guan Y, Potten C, Allen T, Neurath MF, Shroyer NF, Montrose MH, Watson AJM. Identification of epithelial gaps in human small and large intestine by confocal endomicroscopy: A translational study from mouse to man. Gastroenterology. 2007;133:1769-78.
Shroyer NF, Helmrath MA, Wang VY-C, Antalffy BA, Henning SJ, Zoghbi HY. Intestine specific ablation of Mouse atonal homolog 1 (Math1) reveals a role in cellular homeostasis. Gastroenterology. 2007; 132:2478-88.
Shroyer NF, Wallis Shultz D, Venken KJT, Bellen HJ, Zoghbi HY. Gfi1 functions downstream of Math1 to control intestinal secretory cell subtype allocation and differentiation. Genes and Development. 2005;19:2412-7.
Kris A. Steinbrecher, PhD
Inflammatory bowel disease; innate immunity; epithelial cell proliferation and differentiation
Visit the Cohen-Steinbrecher Lab.
PhD: Molecular and Developmental Biology, University of Cincinnati, Cincinnati, OH, 2001.
Postdoctoral Fellowship: Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, 2001-2005.
Waddell A, Ahrens R, Steinbrecher K, Donovan B, Rothenberg ME, Munitz A, Hogan SP. Colonic Eosinophilic Inflammation in Experimental Colitis Is Mediated by Ly6Chigh CCR2+ Inflammatory Monocyte/Macrophage-Derived CCL11. J Immunol. 2011 Apr 15.
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 Jan 31;6(1):e16139.
Steinbrecher KA, Cohen MB. Transmembrane guanylate cyclase in intestinal pathophysiology. Curr Opin Gastroenterol. 2011 Mar;27(2):139-45. 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 Aug;139(2):530-41. Steinbrecher KA, Horowitz NA, Blevins EA, Barney KA, Shaw MA, Harmel-Laws E, Finkelman FD, Flick MJ, Pinkerton MD, Talmage KE, Kombrinck KW, Witte DP, Palumbo JS. Colitis-associated cancer is dependent on the interplay between the hemostatic and inflammatory systems and supported by integrin alpha(M)beta(2) engagement of fibrinogen. Cancer Res. 2010 Apr 1;70(7):2634-43. Garin-Laflam MP, Steinbrecher KA, Rudolph JA, Mao J, Cohen MB. Activation of guanylate cyclase C signaling pathway protects intestinal epithelial cells from acute radiation-induced apoptosis. Am J Physiol Gastrointest Liver Physiol. 2009 Apr;296(4):G740-9. Steinbrecher KA, Harmel-Laws E, Sitcheran R, Baldwin AS. Loss of epithelial RelA results in deregulated intestinal proliferative/apoptotic homeostasis and susceptibility to inflammation. J Immunol. 2008 Feb 15;180(4):2588-99.
Rudolph JA, Pratt J, Mourya R, Steinbrecher KA, Cohen MB. Novel mechanism of cyclic AMP mediated extracellular signal regulated kinase activation in an intestinal cell line. Cell Signal. 2007 Jun;19(6):1221-8. Mann EA, Steinbrecher KA, Stroup C, Witte DP, Cohen MB, Giannella RA. Lack of guanylyl cyclase C, the receptor for Escherichia coli heat-stable enterotoxin, results in reduced polyp formation and increased apoptosis in the multiple intestinal neoplasia (Min) mouse model. Int J Cancer. 2005 Sep 10;116(4):500-5. Steinbrecher KA, Wowk SA, Rudolph JA, Witte DP, Cohen MB. Targeted inactivation of the mouse guanylin gene results in altered dynamics of colonic epithelial proliferation. Am J Pathol. 2002 Dec;161(6):2169-78.
Cynthia C. Wetzel, PhD Program Manager, Digestive Health Center
Program Manager, Digestive Health Center
BS: Biology, College of Mount Saint Joseph, Cincinnati, Ohio, 1994.
PhD: Biomedical Research/Biochemistry and Molecular Biology, Wright State University, Dayton, Ohio, 1999.
Postdoctoral Research Fellowship: Division of Developmental Biology, Cincinnati Children's Hospital Research Foundation, Cincinnati, Ohio, 1999-2002.
Stavra A. Xanthakos, MD, MS Co-Director, Steatohepatitis Center
is focused on identifying the biologic determinants of non-alcoholic steatohepatitis (NASH), including potential gene-environment interactions with dietary intake during childhood and adolescence. One of her long-term research goals is to develop and apply mechanistically based therapies through clinical trials for NASH in childhood and adolescence.
Medical Director, Surgical Weight Loss Program for Teens
Stavra A. Xanthakos, MD, is an assistant professor and attending physician in the Division of Gastroenterology, Hepatology and Nutrition, the co-director of the Cincinnati Children’s Steatohepatitis Center, and the medical director of the Surgical Weight Loss Program for Teens. She also partners with physicians and staff in Cincinnati Children’s Center for Better Health and Nutrition in the evaluation and management of pediatric patients suffering from severe pediatric obesity and related complications.
Dr. Xanthakos received her medical degree from Duke University in 1997 and a Master of Science degree in molecular epidemiology from the University of Cincinnati in 2006. Her post-doctoral training, including residency, chief residency and fellowship were completed at Cincinnati Children's and she joined the faculty in 2005. During her fellowship, Dr. Xanthakos investigated the prevalence and outcome of non-alcoholic fatty liver disease (NAFLD) in young adult women as her master’s thesis in molecular epidemiology. Her current clinical and translational research is focused on identify the predictors and outcome of obesity-related liver disease (nonalcoholic fatty liver disease and steatohepatitis), in obese adolescents undergoing bariatric surgery. She is also a co-investigator in the NIH sponsored Teen LABS, a multicenter consortium investigating bariatric surgery in adolescents and in the NIH-sponsored NASH Clinical Research Network. Additional research interests of Dr. Xanthakos include the treatment and prevention of pediatric obesity, outcomes of bariatric surgery in adolescents, malnutrition in pediatric obesity, as well as identifying genetic and environmental risk factors for pediatric nonalcoholic fatty liver disease to enable better evaluation and treatment options. She also leads clinical quality improvement initiatives in the Steatohepatitis Center, which are aligned with divisional and institutional initiatives to achieve measurable improvements in children’s health and disease outcomes.
Dr. Xanthakos has published extensively in the field of pediatric obesity, bariatric medicine and non-alcoholic fatty liver disease. She regularly is invited to speak about pediatric obesity evaluation and management, particularly bariatric medicine, and pediatric nonalcoholic fatty liver disease.
MD: Duke University, Durham, NC, 1997.
MS: Molecular Epidemiology, University of Cincinnati, 2006.
Residency: Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 1997-2000.
Chief Residency: Cincinnati Children's, Cincinnati, OH, 2000-01.
Clinical Fellowship: Gastroenterology, Hepatology & Nutrition, Cincinnati Children's , Cincinnati, OH, 2001-2004.
Research Fellowship: Molecular Epidemiology in Children's Environmental Health, Masters of Science, 2002-2005.
Certification: Pediatrics, 2008; Pediatric Gastroenterology, 2005.
Carter-Kent C, Alkhouri N, Yerian LM, Brunt EM, Angulo P, Kohli R, Ling SC, Xanthakos SA, Whitington PF, Charatcharoenwitthaya P, Yap J, Lopez R, McCullough AJ and Feldstein AE. The relationship of steatosis grade, zone and type to key histological features in children with nonalcoholic fatty liver disease. Journal of Pediatric Gastroenterology, Hepatology and Nutrition. 2011;52(2):190-7.
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 Sep;52(3):934-44. Kohli R, Boyd T, Lake K, Dietrich K, Nicholas L, Balistreri WF, Ebach D, Shashidhar H, Xanthakos SA. Rapid progression of NASH in childhood. J Pediatr Gastroenterol Nutr. 2010 Apr;50(4):453-6.
Xanthakos SA. Nutritional deficiencies in obesity and after bariatric surgery. Pediatr Clin North Am. 2009 Oct;56(5):1105-21.
Inge TH, Xanthakos S. Sleeve gastrectomy for childhood morbid obesity: why not? Obes Surg. 2010 Jan;20(1):118-20. Inge TH, Jenkins TM, Zeller M, Dolan L, Daniels SR, Garcia VF, Brandt ML, Bean J, Gamm K, Xanthakos SA. Baseline BMI is a strong predictor of nadir BMI after adolescent gastric bypass. J Pediatr. 2010 Jan;156(1):103-108 Xanthakos SA. Bariatric surgery for extreme adolescent obesity: Indications, outcomes, and physiologic effects on the gut-brain axis. Pathophysiology. 2008 Aug;15(2):135-46. Roehrig HR, Xanthakos SA, Sweeney J, Zeller MH, Inge TH. Pregnancy after gastric bypass surgery in adolescents. Obes Surg. 2007 Jul;17(7):873-7. Miller RJ, Xanthakos SA, Hillard PJ, Inge TH. Bariatric surgery and adolescent gynecology. Curr Opin Obstet Gynecol. 2007 Oct;19(5):427-33. Inge TH, Xanthakos SA, Zeller MH. Bariatric surgery for pediatric extreme obesity: now or later? Int J Obes (Lond). 2007 Jan;31(1):1-14.
Adolescent Bariatrics: Assessing Health Benefits and Risks. Co-Investigator. National Institutes of Health. July 2006 - April 2011. #U01DK072493.
Coenzyme Q as a Novel Biomarker for the Severity of Steatohepatitis. Co-Principal Investigator. National Institutes of Health. Jun 2010 - May 2011. #P30DK078392. Biological Determinants of Steatohepatitis after Adolescent Bariatric Surgery. Principal Investigator. National Institutes of Health. July 2008 - June 2013. #1K23DK080888. Clinical Research Network in Non-Alcoholic Steatohepatitis (NASH CRN). Site Principal investigator. National Institutes of Health. Aug 2009 - Apr 2014. #U01DK061732.
Chunyue Yin, PhD
studies the cellular and molecular basis of liver development and disease pathogenesis. She focuses on hepatic stellate cells, the key cell type responsible for hepatic fibrogenesis. She utilizes the zebrafish model to investigate the regulation of hepatic stellate cells during liver development and alcoholic liver injury, and their function in liver regeneration. Research in congenital biliary diseases is a second lab focus.
Visit the Yin Lab.
Liver development; hepatic fibrosis and cirrhosis; hepatic stellate cells; stem cells and regeneration; congenital biliary diseases; zebrafish genetics
Dr. Yin conducted her doctoral research in Dr. Lilianna Solnica-Krezel’s laboratory at Vanderbilt University, where she investigated the molecular regulation of cell movements during zebrafish gastrulation and revealed the impact of gastrulation movements on somite development. In parallel, she participated in a forward genetic screen to identify novel regulators of zebrafish early development. She identified the calamity mutant that exhibits defects in notochord formation and pigmentation. Subsequent positional cloning revealed that a mutation in the atp7a gene, the zebrafish homolog of the human Menkes Disease gene, was responsible for the calamity mutant phenotypes.
With a strong interest in building zebrafish models for human diseases, she decided to conduct her postdoctoral research in Dr. Didier Stainier’s laboratory, which is at the forefront of zebrafish digestive organ research. She received a Postdoctoral Fellowship from the Juvenile Diabetes Research Foundation to study pancreas development in zebrafish hands-off/han mutants that carry a mutation in the transcription factor gene hand2. Her research led to the discovery that the defective pancreatic development in han mutants is due to a failure in asymmetric gut looping. She also showed that gut-looping morphogenesis is dependent on extracellular matrix remodeling and revealed novel roles for Hand2 in this process. This work was published in Developmental Cell in 2010. Her work is now focused on the hepatic stellate cells and hepatic biliary cells. She has developed transgenic lines that mark these cell types and will use them and related reagents to characterize the cellular behaviors of these cells in liver development and disease, as well as the underlying molecular regulations.
BS: Evolution and Ecology, Fudan University, Shanghai, China, 2001.
PhD: Developmental Biology, Vanderbilt University, Nashville, TN, 2007.
Postdoctoral fellow: Developmental Biology, University of California at San Francisco, San Francisco, CA, 2012.
Delous M*, Yin C*, Shin D, Ninov N, Carten JD, Pan L, Ma TP, Farber SA, Moens CB, Stainier DYR. Sox9b is a key regulator of pancreaticobiliary ductal system development. PLoS Genetics. 2012. * These authors contribute equally to this work.
Yin C*, Evason K, Maher JJ, Stainier DYR. The bHLH transcription factor Hand2 marks hepatic stellate cells in zebrafish: analyses of stellate cell entry into the developing liver. Hepatology. 2012. * Co-corresponding author.
Yin C, Kikuchi K, Hochgreb T, Poss KD, Stainier DYR. Hand2 regulates extracellular matrix remodeling essential for gut-looping morphogenesis in zebrafish. Developmental Cell. 2010;18: 973-984.
Yin C, Kiskowski M, Pouille PA, Farge E, Solnica-Krezel L. Cooperation of polarized cell intercalations drives convergence and extension of presomitic mesoderm during zebrafish gastrulation. J Cell Biol. 2008;180: 221-232.
Yin C, Solnica-Krezel L. Convergence and extension movements affect dynamic notochord-somite interactions essential for zebrafish slow muscle morphogenesis. Dev Dyn. 2007;236: 2742-2756.
Yin C, Solnica-Krezel L. Convergence and extension movements mediate the specification and fate maintenance of zebrafish slow muscle precursors. Dev Biol. 2007;304(1): 141-155.
Mendelsohn B*, Yin C*, Wilm T, Johnson S, Solnica-Krezel L, Gitlin J. Atp7a determines a hierarchy of copper metabolism during embryogenesis essential for notochord development. Cell Metabolism. 2006;4(2):155-62. * These authors contributed equally to this work.
Lin F, Sepich DS, Chen S, Topczewski J, Yin C, Solnica-Krezel L, Hamm H. Essential roles of Gα12/13 signaling in distinct cell behaviors driving zebrafish convergence and extension gastrulation movements. J Cell Biol. 2005;169(5): 777-787.
Marlow F, Gonzalez EM, Yin C, Rojo C, Solnica-Krezel L. No tail co-operates with non-canonical Wnt signaling to regulate posterior body morphogenesis in zebrafish. Development. 2004;131(1): 203-216.
Yin C, Qian J, Fu C, Ma Y, Zheng S, Mao Y. Genetic diversity in natural populations of glycine tabacina in Fujian, China. J Gen Mol Biol. 2002;13: 6-12.
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