Pathologic Markers of Genetic Damage and Disease in IBD

Summary

Principal Investigator: Melvin B Heyman
Abstract: This application is for continuation and extension of pilot studies conducted at the University of California, San Francisco (UCSF), Children's Hospital & Research Center of Oakland (CHRCO), and the Children's Environmental Health Laboratory at the University of California at Berkeley (UCB). This investigation has identified a relationship between active inflammatory bowel disease (IBD) and genetic injury, particularly in pediatric patients with Crohn's Disease (CD), and has generated preliminary evidence of biomarkers of genetic injury that may signal susceptibility to cancer in children and adolescents with IBD. In the course of these studies, procedures were established for patient recruitment, sample collection, and specimen processing at the 3 sites. Based on the above scientific and operational results, 5 additional IBD centers associated within the Pediatric IBD Consortium - Texas Children's Hospital (Baylor), Children's Hospital of Philadelphia, Emory University, MassGeneral Hospital for Children, and the University of Chicago Children's Hospital - have agreed to collaborate with UCSF, CHRCO and UCB to continue this project. The present R03 proposal is to utilize the clinical resources of the 7 cooperating centers to prospectively provide the required number of newly diagnosed and untreated pediatric CD patients and matched controls to confirm: (1) the relationship between cytogenetic damage and CD; (2) the relationship of cytogenetic damage to disease activity (Pediatric Crohn's Disease Activity Index [PCDAI]) or folate deficiency; and (3) the correlation of methylenetetrahydrofolate reductase (MTHFR) polymorphisms with a) the risk of CD, b) cytogenetic damage, and c) folate, vitamin B12, and homocysteine levels. Blood and buccal cell specimens will be collected in each collaborating center and shipped to UCB for processing using standardized and validated methods. Cytogenetic damage will be assessed by micronucleus analysis of epithelial cells collected from buccal mucosa of patients and controls, and findings compared with hematological markers of cytogenetic injury in lymphocytes from the same subjects. In summary, the proposed project is designed to take advantage of the unique patient population of the Pediatric Inflammatory Bowel Disease Consortium and of the specialized laboratory facilities at UCB to elucidate the pathogenetic mechanisms, evolution, and prognosis of pediatric IBD.
Funding Period: 2004-09-30 - 2008-07-31
more information: NIH RePORT

Top Publications

  1. ncbi Predictors of proctocolectomy in children with ulcerative colitis
    Lorraine I Kelley-Quon
    Mattel Children s Hospital, CA, USA
    J Pediatr Gastroenterol Nutr 55:534-40. 2012
  2. pmc Micronuclei in neonates and children: effects of environmental, genetic, demographic and disease variables
    Nina Holland
    School of Public Health, 733 University Hall, University of California, Berkeley, CA 94720 7360, USA
    Mutagenesis 26:51-6. 2011
  3. pmc Cytokine profiles in peripheral blood of children and adults with Crohn disease
    Seung Pak
    School of Public Health, University of California, Berkeley, CA, USA
    J Pediatr Gastroenterol Nutr 54:769-75. 2012
  4. pmc Reduced intracellular T-helper 1 interferon-gamma in blood of newly diagnosed children with Crohn's disease and age-related changes in Th1/Th2 cytokine profiles
    Nina Holland
    School of Public Health, University of California, San Francisco, California 94143, USA
    Pediatr Res 63:257-62. 2008
  5. pmc Folate concentrations in pediatric patients with newly diagnosed inflammatory bowel disease
    Melvin B Heyman
    Department of Pediatrics, University of California, San Francisco, San Francisco, CA 94143 0136, USA
    Am J Clin Nutr 89:545-50. 2009

Scientific Experts

  • Nina Holland
  • Melvin B Heyman
  • Lorraine I Kelley-Quon
  • Seung Pak
  • Howard C Jen
  • Harland S Winter
  • George D Ferry
  • Uma Mahadevan
  • Bittoo Kanwar
  • Elizabeth Mileti
  • Elizabeth A Garnett
  • David A Ziring
  • Barbara S Kirschner
  • Stephen B Shew
  • Stanley A Cohen
  • Neera Gupta
  • Rachel Beckert
  • Benjamin D Gold

Detail Information

Publications5

  1. ncbi Predictors of proctocolectomy in children with ulcerative colitis
    Lorraine I Kelley-Quon
    Mattel Children s Hospital, CA, USA
    J Pediatr Gastroenterol Nutr 55:534-40. 2012
    ..The purpose of the present study was to identify clinical predictors associated with surgery in children with UC using a disease-specific database...
  2. pmc Micronuclei in neonates and children: effects of environmental, genetic, demographic and disease variables
    Nina Holland
    School of Public Health, 733 University Hall, University of California, Berkeley, CA 94720 7360, USA
    Mutagenesis 26:51-6. 2011
    ..Emerging 'omic' and other novel molecular technologies may shed light on the molecular mechanisms and biological pathways associated with the MN levels in children...
  3. pmc Cytokine profiles in peripheral blood of children and adults with Crohn disease
    Seung Pak
    School of Public Health, University of California, Berkeley, CA, USA
    J Pediatr Gastroenterol Nutr 54:769-75. 2012
    ..The present pilot study examines the hypothesis that cytokine profiles differ between pediatric and adult patients with CD...
  4. pmc Reduced intracellular T-helper 1 interferon-gamma in blood of newly diagnosed children with Crohn's disease and age-related changes in Th1/Th2 cytokine profiles
    Nina Holland
    School of Public Health, University of California, San Francisco, California 94143, USA
    Pediatr Res 63:257-62. 2008
    ..In future studies of pediatric IBD patients, it will be critical to consider the effect of age and disease progression on cytokine status in intestinal mucosa and peripheral blood...
  5. pmc Folate concentrations in pediatric patients with newly diagnosed inflammatory bowel disease
    Melvin B Heyman
    Department of Pediatrics, University of California, San Francisco, San Francisco, CA 94143 0136, USA
    Am J Clin Nutr 89:545-50. 2009
    ..Folate deficiency has been shown to be associated with inflammatory bowel disease (IBD). However, folate concentrations are poorly delineated in children with IBD...