Inflammatory Bowel Disease (IBD) Center Biobank Research

A variety of biobank research is conducted through the IBD Center.

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Current Projects

IBD and Intestinal Diseases Biobank Expand answer

Investigators: Sue Deiling, Leonard Harris, Katie Schieffer, Stephen Matthews, Melanie Eshelman, Mathew Coates, MD, PhD, David Stewart, MD, Gregory Yochum, PhD, Walter Koltun, MD

Unifying hypothesis: The most effective translational research is that using DNA and other human material harvested from patients with the disease process under investigation.

Summary: An IRB approved tissue bank repository (BioBank) was started in 1998, originally used to study the genetics of Inflammatory Bowel Disease (IBD). Since this beginning, additional patient recruitment has allowed investigations into other intestinal diseases, including diverticulitis, colorectal cancer and hereditary polyposis syndromes. After signed patient informed consent, DNA and RNA from blood and surgically harvested tissue samples are taken and stored with the goal of investigating the genetics and tissue consequences of these various disease processes. We recruit all patients with IBD, and all patients that undergo surgery. Each blood sample collected has several aliquots “banked” in four different storage media. Similarly, diseased and non-diseased tissue from each part of the colon or intestine is stored in several different storage media. Thus, each surgical case could involve from one to 56 samples to store. Such availability of DNA and tissue allow for not only genetic discovery, but also how such genetic alterations affect the individual’s physiology at the tissue level. Recently, the BioBank has expanded to include biopsy samples from IBD patients taken at the time of endoscopy. Currently the BioBank has more than 3,000 recruited patients. We are currently recruiting approximately 40 patients a month, and collecting tissue from 35 surgical cases a month.

Collaborators: James Broach, PhD (Institute for Personalized Medicine), Milena Bogunovic, MD, PhD (Microbiology and Immunology), Kristin Eckert, PhD (Experimental Pathology and Biochemistry and Molecular Biology), Vijay Kumar, PhD (Nutritional Sciences)

Demographic Characteristics of Crohn's Patients in the Penn State Biobank Expand answer

Investigator: Sue Deiling

Summary: Review de-identified demographic data for Crohn’s patients seen by the Penn State Hershey IBD Center between 2012 and 2015 to identify patterns of disease distribution, health care delivery and changes in such over time.

Unifying Hypothesis: There is an increasing need for specialty IBD care needed in the Central Pennsylvania area that is being provided by the Penn State IBD Center.

Collaborators: John Ebeid, undergraduate student of Biology at the University of Scranton, PA

SNPs associated with Inflammatory Bowel Disease demarcate transcriptional regulatory elements Expand answer

Investigators: Stephen Matthews, Leonard Harris, Sue Deiling, Walter Koltun, Gregory Yochum

Hypothesis: IBD-associated SNPs that map to gene poor regions in the human genome demarcate DNA regulatory elements termed enhancers.

Summary: Using publically available datasets, we have identified numerous regions of the genomes that overlap with SNPs associated with a predisposition to developing IBD. We are testing whether these are transcriptional regulatory regions, identify the pathways involved in their regulation, and ascertaining target genes using samples obtained from the Biobank.

Microbiota changes contribute to diverticulitis Expand answer

Investigators: Katie Schieffer, Gregory Yochum, David Stewart

Hypothesis: Consistent microbiota changes in bacterial and fungal communities are associated with diverticulitis in human subjects, and are predictive of complicated forms of this disease.

Summary: Diverticulitis, by definition, involves a bacterial infection of the colon, therefore the microbial milieu is relevant to the disease process. The present study seeks to evaluate this microbial milieu in patients with diverticulitis, a here to for, understudied area of research. 16s RNA and ITS (internal transcribed spacer) sequencing will be performed on tissue samples of diverticular surgical specimens which have been stored in the colorectal biobank. Those bacterial and fungal community structures associated with diverticulitis, and disease related complications, will be sought.

Collaborators: Gina Lamendella, PhD (Juniata College)

Funding: Peter and Marshia Carlino Fund for IBD research

The Microbiota Composition of the Ileum and Colon Prior to Ileal Pouch Anal Anastomosis (IPAA) Can Predict Pouchitis Development Expand answer

Investigators: Katie Schieffer, Walter Koltun, Matthew Coates

Hypothesis: The presence or absence of specific bacterial populations in the ileum and colon prior to IPAA can predict the onset of pouchitis.

Summary: Recently, a study identified specific bacterial species present or absent in fecal samples prior to colectomy and IPAA capable of predicting pouchitis development (Machiels et al. 2015 Gut). Analysis of tissue samples will provide a better representation of causative bacterial species since fecal samples do not account for bacteria attached to the mucosal and tissue layers. This retrospective study will analyze the microbiota composition of stored Biobank tissue ileum and colon from patients who underwent colectomy and IPAA for ulcerative colitis and familial adenomatous polyposis by 16S rRNA sequencing. We will appropriately identify patients who have developed pouchitis since colectomy and compare to a matched control population without pouchitis.

Collaborators: Gina Lamendella (Juniata College), Justin Wright (Juniata College)

Multifocal Diverticulitis Expand answer

Investigators: Christine Choi, David Stewart, Walter Koltun

Hypothesis: Multifocal diverticulitis represents a more severe form of diverticulitis that has a genetic predisposition. Analysis of SNPs on the custom microarray will demonstrate specific SNPs shared by multifocal diverticulitis.

Summary: Diverticulitis has widely variable clinical presentations requiring varying degrees of medical and surgical management. The clinical importance of multifocal diverticulitis, which we defined as synchronous or metachronous diverticulitis occurring in different locations within the colon, has not been previously recognized, nor studied. This retrospective study identified patients with multifocal diverticulitis to determine clinical characteristics and surgical outcomes. Available genotype information from the Colorectal Biobank was analyzed to determine whether this under-recognized clinical entity could have a genetic basis.

Collaborators: Arthur Berg, PhD (Associate Professor of Biostatistics and Bioinformatics, Director of the Bioinformatics Core, Director of the PhD program in Biostatistics, Leader of the CTSI Biomedical Informatics Program)

Viral involvement in the pathogenesis of diverticulitis Expand answer

Investigators: Katie Schieffer, Leonard Harris, Sue Deiling, Gregory Yochum, Walter Koltun

Hypothesis: Viruses contribute to the persistent inflammation associated with diverticulitis.

Summary: Using RNA-Sequencing of full-thickness colonic tissues obtained from individuals with diverticulitis and those from control individuals lacking diverticular disease, we found that pathways associated with the host response to viral infections were upregulated in inflamed (diseased) tissue. By searching for virus-specific transcripts in the Seq data, we will identify the putative virus(es) involved, confirm their presence using alternative methodology, and perform retrospective analyses with Biobank tissues to correlate viral load with disease outcomes.

Collaborators: Jianming Hu, PhD (Microbiology and Immunology), Anna Salzberg (Institute for Personalized Medicine)

Funding: Pending CTSI grant