Diseases of the Colon and Rectum
Presentation at the November 19, 2007 NCDD Meeting
Chair: Joanne A. P. Wilson, MD
Vice Chair: Nancy J. Norton
Research Goal 1
Establish mechanisms of colon injury and repair with development of therapeutic interventions.
Research Goal 1
Objectives
Research Goal 1
Objectives (continued)
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Determine the bioavailability, safety, and efficacy of orally-administered trefoil factors (TFFs) and other epithelial cell growth factors in models of mucosal injury and inflammation.
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Develop strategies for mimicking the enteric antigen/Toll-like receptor interactions to promote gut healing.
Research Goal 1
Objectives (continued)
Research Goal 2
Understand colonic mucosal absorption in health and disease.
Research Goal 2
Objectives
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Survey known sodium, chloride, short chain fatty acid and ammonia transporter expression in human colon with comparison to murine models and evaluate segmental alterations in transporter expression on varied defined fiber and protein diets.
Research Goal 2
Objectives (continued)
Research Goal 2
Objectives (continued)
Research Goal 3
Determine the role of gut microflora in health and disease states of the colon.
Research Goal 3
Objectives
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Establish tissue banks of mucosal biopsies to allow large-scale,chip-based comparison of adherent bacteria to the surface epithelium (biofilm) to bacteria in the normal flora in feces.
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Compare bacterial flora in obese and lean humans using molecular fingerprint assays and sequence analysis of cloned 16S ribosomal DNA.
Research Goal 3
Objectives (continued)
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Compare colonic microflora before and after antibiotics inpatients with and without colonization by C. difficile, and use these data to develop a rational approach to reconstitute the microflora.
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Conduct randomized, double-blind, controlled trials to manipulate the colonic microflora in obesity as a possible adjunct therapy.
Research Goal 4
Establish the cause of diverticular disease and its complications with modulation of disease.
Research Goal 4
Objectives
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Identify risk factors for diverticular disease including genetics and life style and association with complications (specifically diverticulitis and bleeding).
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Determine whether treatment with non-absorbable antibiotics, mesalamine, probiotic agents, prebiotic agents or other agents reduces the risk of recurrent diverticulitis and is cost effective.
Research Goal 4
Objectives (continued)
Research Goal 4
Objectives (continued)
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Determine whether changes in lifestyle, especially diet, reduce the prevalence of diverticulosis and its complications (i.e.,specifically, avoidance of specific dietary factors such as seeds and popcorn), and reduce the risk of diverticulitis.
Research Goal 5
Understand mechanisms and early diagnosis of colonic ischemia and angioectasia.
Research Goal 5
Objectives
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Devise a means of diagnosing colonic ischemia early (i.e., before infarction ensues) and differentiation from other disorders by developing biomarkers for this disease process.
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Determine the underlying, proximate cause of colonic ischemia, especially with regard to the behavior of colonic arteriolar and venular microvasculature and the relationship of the bowel vasculature to serotonergic agents.
Research Goal 6
Improve management of anorectal disorders.
Research Goal 6
Objectives
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Understand risk factors and preventive strategies for anal disorders including anal fistulas, hemorrhoids and fecal incontinence with appropriate modification: natural history and impact of obstetrical sphincter injury, medical and neurological conditions, and pelvic surgery and the role of surgical repair of sphincter defects.
Research Goal 6
Objectives (continued)
Research Goal 6
Objectives (continued)
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Develop educational tools for providers and the public to raise awareness of the impact of fecal incontinence and treatment options, anal abscess, anal fistula and hemorrhoids with particular focus on accurate diagnosis, initial treatment and prevention.
Research Goal 7
Reduce the frequency and severity of radiation injury to the colon.
Research Goal 7
Objectives
Research Goal 8
Determine causes of appendicitis and modulate the course of the disease.
Research Goal 8
Objectives
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Study the effect of dietary factors especially fiber content, prebiotics, probiotics, bowel function (constipation) on the incidence of appendicitis especially in children.
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Develop diagnostic tests, identify biomarkers
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Develop antibiotic Rx
Major Challenges/Steps To Achieve Goals
Major Challenges/Steps To Achieve Goals
Collaboration With Industry
Major Challenges/Steps To Achieve Goals
Research Resources
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Centralized resources for sharing of biological samples and patient data
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A comprehensive tissue bank to collect, store, and disseminate normal and diseased human colonic specimens defined with respect to anatomic segment and clinical data
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Database capabilities and clinical consortia for randomized clinical trials with standardized endpoints
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A systems-based approach to the study of colonic transport using defined cultured cell and transgenic mouse models and comprehensive expertise in cell biology, structural biology, transepithelial transport, nutrition, imaging, and computational modeling
Major Challenges/Steps To Achieve Goals
Research Tools for the Microbiome
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Use of mucosal biopsies from colonoscopy rather than the traditional reliance on stool specimens
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New technology development for measurement of the metabolome of the colonic flora
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Metabolomic techniques to study the human or animal microflora in vivo using non-invasive methods such as breath analysis
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Robust databases and software tools to analyze large amounts of data from multiple laboratories
Clinical Research
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Clinical research studies comparing different populations to define the risk factors for diverticular disease and to distinguish symptomatic diverticular disease from irritable bowel syndrome
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Methods to control differences in diet among participants in trials for diverticular disease
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Central resources for diseases that are difficult to study in a single center with limited access to patients, such as radiation colitis
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Clear criteria for distinguishing acute and chronic fissures on examination and better means to diagnose the etiology of symptoms
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Methods to overcome the reluctance of patients to discuss their symptoms and the reluctance of providers to inquire about these symptoms
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Innovative approaches to research collaboration on appendicitis.
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New methods to obtain accurate dietary histories in patients,including children
Animal Models
Page last updated: January 07, 2008