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New research at the Chapman School of Pharmacy could help diagnose and treat genetic disorders

Most human cells have antenna-like protrusions called primary cilia that emerge from cell surfaces. These microscopic structures efficiently detect mechano-biofluid flux and its contents across cell surfaces in single-celled organisms.

But when they are defective in mammals, organ function is negatively affected, giving rise to several devastating genetic disorders or ciliopathies. Among them is polycystic kidney disease, which affects approximately 500,000 people in the United States.

Ashraf Mohieldin, Ph.D.

New research by scientists at Chapman University School of Pharmacy (CUSP) offers valuable insight into mechanical misfire that could be linked to faulty primary cilia. Ashraf Mohieldin, Ph.D., an associate researcher at Chapman University School of Pharmacy and principal investigator on the study, led a team to examine and analyze the characteristics of primary cilia excretions, called extracellular vesicles or VE. Their findings were published in The Journal of Extracellular Vesicles.

The key to these findings was the discovery of a new classification of ciliary EV, which has a biomarker and unique characteristics different from its counterparts (other EVs). Biomarkers may eventually lead to the development of diagnostic tests for related diseases.

Additionally, these findings confirm previous research by Mohieldin’s team and others that IV secretion from primary cilia plays a role in cardiovascular regulations, including blood pressure, cardiac arrhythmia, heart failure, and hypertrophy. It turns out that the cilia release electric vehicles to communicate with surrounding cells and organs in the body. Lack of such communication skills will disrupt various cellular processes resulting in a disorder of ciliopathy.

“These findings will be important in advancing our understanding of human genetic diseases and investigators will be able for the first time to selectively examine the pathogenesis associated with this newly classified ciliary EV,” said Mohieldin.

Moving forward, Mohieldin’s team will use a translational animal model to develop a comprehensive understanding of the physiological role of ciliary electric vehicles in patients with ciliopathy disorders, using new multimodal animal platforms, the latest generation of ParaVision 6 software, and an MRI. newly purchased (MRI) which allows safe live animal studies and limits the number of animals used in this work.

Chapman invested $ 2.5 million in purchasing the MRI. Along with a recently expanded vivarium facility, Chapman and the School of Pharmacy are positioned to provide further breakthroughs in biomedical translation research.

The work was supported, in part, by grants from the National Institutes of Health, the American Heart Association, and Chapman. Scripps Research scientists James J. Moresco and John R. Yates, supported by the National Institute of General Medical Sciences, collaborated.

Published results can be read at the Wiley Online Library.

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