Shehzad Sheikh, MD, PhD

Shehzad Z. Sheikh, MD, PhD, associate professor of medicine in the division of gastroenterology and hepatology, and post-doctoral fellow Takahiko Toyonaga, MD, PhD, have received a fellowship research award from the Crohn’s & Colitis Foundation.

Sheikh and Toyonaga are investigating novel diagnostic and therapeutic approaches in patients with inflammatory bowel diseases (IBD), seeking to understand the role of genetics in the development of IBD and response to therapy. The project “Increased epithelial cell miR-31 expression disrupts the intestinal barrier in Crohn’s Disease” will clarify the impact of increased micro RNA expression in intestinal epithelial cells found in the colon, along with its effect on intestinal biology in Crohn’s Disease (CD).

“Crohn’s Disease is a lifelong disease characterized by a fluctuating course of gastro-intestinal inflammation, with repeated flares and remissions,” Sheikh said. “Over the last 50 years, incidences at all ages have increased throughout the world, indicating its emergence as a global disease.”

“The aim of our project is to understand how the protective barrier function within the intestine is disrupted in Crohn’s Disease, and how to identify which patients are at high risk of developing severe disease complications.”

Takahiko Toyonaga, MD, PhD

In previous studies, the Sheikh Lab determined that genes, and a special type of molecules referred to as a micro RNA (miRNA), are expressed differently in the colons of CD patients compared to unaffected individuals. Researchers found that one specific molecule, miR-31-5p, could classify CD patients into two distinct subclasses, and that miR-31-5p is more highly expressed in a specific cell type in the colon called intestinal epithelial cells (IECs), primarily responsible for the protective intestinal barrier function. Further, researchers found the increased miR-31-5p expression appears to disrupt the proper development of IECs.

Researchers will consider the impact of increased expression of miR-31-5p on the function of IECs, to determine whether increased miR-31-5p expression contributes to the development of disease complications in CD patients. Findings will unravel mechanisms that disrupt the ability of intestinal cells to mature properly in CD, leading to a leaky barrier and uncontrolled inflammation. These findings will lay the ground work in developing a potentially important diagnostic and prognostic marker for the disease. This award provides salary support and research monies to Toyonaga, a visiting assistant professor from Japan, trained in clinical IBD, to focus and advance the research proposed.