The Penn State Hershey Inflammatory Bowel Disease Program is committed to the study of Crohn’s Disease and Ulcerative Colitis. Our team of physicians and specialists work together to focus on improving the quality of life for its patients by participating in cutting-edge national research.
Determining the Genes Relevant to IBD
Research suggests that IBD results from a combination of certain genetic variations, environmental factors, and the presence of bacteria in the digestive tract. IBD tends to cluster in families and having an affected family member is a significant risk factor for the disease. The old idea that IBD is either Crohn's disease or ulcerative colitis is now being refined into smaller categories of "disease subtype", based on the presence or absence of individual mutations in various genes. In addition to genetic studies, we are also investigating epigenetic mechanisms in IBD. Epigenetic changes can cause inheritable patterns of gene expression and function without changing the genetic sequence. These changes can be caused by environmental factors (age, diet, smoking, infections, medications). The goal of this study is to identify and characterize the genes and epigenetic changes involved in causing IBD and related conditions (pyoderma gangrenosum, colorectal cancer).
Investigators
Walter A Koltun M.D.
Zhenwu Lin, Ph.D.
Sources of Support
- Philadelphia Health Care Trust
- The Carlino fund for IBD research at the Milton S. Hershey Medical Center
- Children's Miracle Network
- Penn State Milton S. Hershey Medical Center Surgery Research Feasibility Grants
Identifying Genes that Predict Surgical Outcome
Little work has focused on how genetic discoveries can assist the surgeon in surgical decision making. Ileoanal pouch anal anastomosis (IPAA) is the surgical procedure of choice for many ulcerative colitis patients who need a proctocolectomy. Pouchitis and Crohn’s disease-like complications are two adverse post-surgical conditions that confound the success of IPAA surgery. We hypothesize that genetic variation (and subtypes of clinical phenotype) may explain the different outcomes associated with the Ileal Pouch Anal Anastomosis (IPAA) procedure and in addition, could aid in classifying ileocolic CD patients into high and low risk of recurrence groups as defined by the more frequent need for ileocolectomy. These findings can potentially be used as a “gene signature” to predict post-operative complications and aid in surgical decision making.
Walter A Koltun MD
Lisa S. Poritz MD
Sources of Support
ASCRS - International Research Fellow Grant
Alteration of the Tight Junction Proteins in IBD
The intestinal regulates movement of nutrients and water and its barrier function is maintained by intestinal “tight junction” proteins. IBD patients demonstrate increased intestinal permeability (“leakiness”) due to a decreased barrier function. It is suggested that a barrier defect may facilitate the development of inflammatory infiltrate and lead to IBD progression. This study investigates the expression and function of intestinal tight junction proteins in intestinal cells, inflamed mucosal tissues, and animal IBD models. We also study the function of IBD-associated gene variants on tight junction function.
Lisa S. Poritz MD
Sources of Support
2010 Mentored Clinical Scientist Research Career Development Award (K08
Function of the IBD-Associated Gene (Nkx2-3) in the Intestine
Nkx2-3 is an intestinal gene strongly associated with both Crohn’s disease and ulcerative colitis. Little is currently known about the function of Nkx2-3 in humans; however this gene is known to belong to a group of genes that control the expression of other genes. This project aims to identify the genes and cellular pathways controlled by Nkx2-3 in the human intestine and their relation to cause and progression of IBD. We are studying the function of this gene in intestinal inflammation using human intestinal microvascular cells.
Zhenwu Lin PhD
Sources of Support
- Philadelphia Health Care Trust
- The Carlino fund for IBD research at the Milton S. Hershey Medical Center
- Penn State Milton S. Hershey Medical Center Surgery Research Feasibility Grants
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