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NIH grant funds study to examine long non-coding RNA molecules role in defense from cryptosporidium

CryptoResearcher Xian-Ming Chen, MD, a professor in the Department of Medical Microbiology and Immunology at Creighton University’s School of Medicine has received a $1.8 million NIH grant to find how long non-coding RNA molecules are involved in the host defense in the intestinal tract from cryptosporidium.

Cryptosporidiosis is one of the leading causes of waterborne disease in the United States and the common cause of diarrhea in young children in developing countries. Public swimming pools and daycares across the country are closed every year due to the disease. Most people recover within a couple of weeks. However, for those with compromised immune systems, particularly those with late stage diagnosed HIV and other immune deficiencies, infection can result in persistent, debilitating and possibly fatal diarrhea and wasting. There is currently no known fully effective treatment available.

IFN-γ is a major immune-modulating molecule, required for preventing development of intestinal cryptosporidiosis. What remains unknown is the key cellular regulatory elements that determine IFN-γ-mediated intestinal epithelial anti-cryptosporidium defense, and its association with the high susceptibility of infection in AIDS patients and young children.

Long non-coding RNAs are a group of newly identified RNA molecules that don’t encode proteins.

“Discovering how they are involved in the IFN-γ-mediated defense of the intestinal tract could lead to a new, targeted approach in treatment for cryptosporidiosis,” said Ming. “RNA-mediated epithelial defense may also present a new arm of mucosal immunity in the digestive tract, important in mucosal antimicrobial defense in general.”

The study will look at how long non-coding RNAs and their RNA-binding partners preferentially expressed in neonatal epithelial cells and in cells during HIV infection modulate IFN-γ-mediated epithelial anti-cryptosporidial defense. Ming said he hopes the study will fill the gaps in the understanding of how epithelial cells orchestrate mucosal anti-cryptosporidium defense, relevant to the development of potential new therapeutic strategies.

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