Gene Expression in Inflammatory Bowel Disease

Progress has been made in recent years in understanding the pathological mechanisms of IBD,
particularly in the search of IBD susceptibility genes. However, due to the extreme
complexity of the diseases, there is still a long way ahead in elucidating detailed molecular
mechanisms of IBD pathogenesis and identifying more effective therapeutic targets. Therefore,
it is the goal of this research study to discover genetic, microbial, gene expression and
serological factors involved in the pathogenesis of IBD which may pave the way for the
identification of more effective therapeutic targets.

The specific aims for these objectives are as follows:

AIM 1: Identify proteins that are changed in expression and post-translational modification
in the intestinal mucosa of patients with active UC or CD compared to i) uninvolved
intestinal mucosa from the same patients, ii) normal intestinal mucosa in control subjects,
and iii) infectious/Inflammatory colitis (C. difficile colitis).

AIM 2: Identify changes in the expression of intestinal membrane transporters for Na
absorption and Cl secretion, including NHE3, in the intestinal mucosa of patients with active
UC or CD compared to i) uninvolved intestinal mucosa from the same patients, ii) normal
intestinal mucosa in control subjects, and and iii) infectious/Inflammatory colitis (C.
difficile colitis). The targeted screening will also include several intestinal epithelial
brush border-associated PDZ-containing proteins that have been recently shown to regulate
trafficking and activity of membrane transporters.

AIM 3: Enteroid Sub-study - To compare the physiologic regulation of Na absorption, Cl
secretion, protein secretion and other intestinal physiologic processes in IBD cases, other
infectious colitis cases and healthy controls as these processes are often altered with
disease activities. The processes will be studied through the development of self-propagating
culture models called organoids or enteroids. The culture models are developed from biopsy
specimens taken from the upper small intestine, including duodenum and jejunum , lower small
intestine (ileum) and proximal and distal colon and used to grow organoids/enteroids. These
are mini-intestines that have the entire crypt villus axes which grow in culture and can be
kept alive indefinitely in culture.

AIM 4: Mechanism of Intestinal Inflammation Sub-study - To understand the mechanisms involved
in the recurrence of inflammation following ileal resection surgery for Crohn's disease (CD).
Reasons for recurrence are currently unknown but are believed to be caused by an interaction
of genetic, immune and microbial features. Information gained from this study will be used to
build a predictive model to identify those patients at greater risk of rapid recurrence, and
will aid physicians in tailoring follow-up treatments.

AIM 5: UC Demarcation Sub-study - To gain further understanding of the mechanisms involved in
the susceptibility to and flare of inflammation in UC patients. Blood, stool, urine, saliva,
lavage and tissue samples from UC patients will be used to help study the genetic, microbial,
metabolic, and immune factors involved in the remission and flare of disease. Information
gained from this study will also be used to build a predictive model of which patients are at
greater risk of disease flare, and which are less likely to do so, allowing physicians to
tailor follow-up treatments accordingly.

Inclusion Criteria:

- All persons, regardless of IBD affection status, greater than 7 years of age
undergoing upper or lower endoscopy or bowel resection

Exclusion Criteria:

- Persons with bleeding tendencies

- Persons on anti-coagulation therapy or who will be place on anti-coagulation therapy
following the planned endoscopy procedures