Basic Science 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:

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.

Investigators:

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.

Investigator:

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.

Investigator:

  • Zhenwu Lin, Ph.D.

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

Panel of Genetics Markers Offers an Effective Method of Differentiating Crohn's Disease from Ulcerative Colitis Patients Undergoing Surgical Treatment

Surgical treatment for the two main forms of IBD, CD and UC is often different due to the non-continuous inflammation of CD, CD's tendency to cause fistuli and abscesses and its likelihood of affecting the small bowel. UC and CD share similar symptoms and clinical features. At times it is difficult to determine a diagnosis of UC versus CD through traditional clinical tests leading to difficulty in surgical decision making.  The aim of this study is to determine genetic markers in the form of single nucleotide polymorphisms (SNPs) that predict the likelihood that a patient has either UC or CD. This is a collaborative effort between Dr. Koltun's lab in the Division of Colorectal Surgery and Dr. Berg and colleagues from the Department of Biostatistics utilizing DNA samples from the IBD Biobank.

Investigators:

Proteomic Markers of Neoplastic Degeneration in Ulcerative Colitis

This study aims to identify protein markers of dysplasia and carcinoma in the serum of ulcerative colitis patients. This is a retrospective study using 2 dimensional difference gel electrophoresis (2-D DIGE) and MALDI-T0F (Matrix Assisted Laser Desorption Ionization Time of Flight)/ToF Mass Spectrometry to analyze the changes in a series of serum proteomic profiles before and after total proctocolectomy (TPC) in the UC patients with and without CRC/dysplasia. This is a collaborative project between Dr. Koltun's lab in the Division of Colon and Rectal Surgery and Dr. Phelps' lab in the Department of Pediatrics.

Investigators: