The Department of Medicine is pleased to announce that Karam Aboudehen, Ph.D., Assistant Professor of Medicine, Division of Nephrology and Hypertension, has received Notice of Award for his PKD (Polycystic Kidney Foundation) grant: Deciphering the role of the long noncoding RNA Pvt1 in ADPKD.
Learn more about this important PKD funded research:
Project Summary:
Despite remarkable advances in our understanding of ADPKD in the last few decades, the disease still has a devastating impact on affected families and society in general. Every year, thousands of people are diagnosed with ADPKD worldwide; therefore, there is an urgent need to further investigate the molecular mechanisms and develop more effective therapies that can positively impact the life and health of individuals with ADPKD. Long noncoding RNAs (LncRNAs) are a class of non-protein coding RNAs with pivotal functions in development and disease. They have emerged as an exciting new drug target category for many common conditions. However, the role of lncRNAs in ADPKD has been understudied. This proposal will determine the impact of a known, highly conserved, and pathogenic lncRNA, called PVT1, on ADPKD pathogenesis. Our proposed assays are based on strong preliminary data showing that Pvt1 silencing reduces cyst growth in cultured kidneys from Pkd1-null mouse embryos. We will utilize pre-clinical models of mouse and human ADPKD to determine whether inhibition of PVT1 ameliorates cystogenesis. One protein that is known to be regulated by PVT1 and plays a critical role in advancing ADPKD is c-MYC. c-MYC is an attractive drug candidate; however, targeting c-MYC remains a challenge. Our proposal provides a complementary approach to traditional drug development in ADPKD. This approach focuses on targeting a single lncRNA to manipulate multiple genes, proteins, and pathways. Should we succeed, it would open the door for exploring the therapeutic potential of inhibiting PVT1 and reducing c-MYC levels to ameliorate cystogenesis in ADPKD.
Biography:
Karam Aboudehen is an Assistant Professor in the Department of Medicine, Division of Nephrology, at Stony Brook University (SBU). In 2012, he completed his graduate training at Tulane University under the guidance of Dr. Samir El-Dahr in Pediatric Nephrology. He then joined Dr. Peter Igarashi laboratory as a post-doctoral fellow at the University of Texas Southwestern Medical Center in Dallas. In 2016, Dr. Aboudehen was appointed to a faculty position at the University of Minnesota before recently joining the Nephrology Division at SBU in 2022. Research in Aboudehen’s lab focus on investigating the role of long noncoding RNAs (lncRNAs) in polycystic kidney disease (PKD). The long-term objective is to discover therapeutically targetable lncRNAs that prevent or mitigate cyst formation and/or progression in PKD. His lab utilizes cutting edge technologies that include mouse molecular genetics, next generation sequencing and mass spectrometry, genetic engineering, RNA pulldown assays, and viral gene delivery.
Congratulations to Dr. Aboudehen, and learn more about the research in the Aboudehen Lab here.
