Dr. Ramchandran to Study Novel Regulatory Mechanisms for a Gene Involved in Vascular Anomalies

Dr. Ramchandran to Study Novel Regulatory Mechanisms for a Gene Involved in Vascular Anomalies

The Medical College of Wisconsin (MCW) has received a four-year, $1.8 million dollar grant from the National Institutes of Health’s National Heart, Lung and Blood Institute to study the RNA regulatory mechanisms underlying genes involved in vascular anomalies.

Ramchandran_242x140Ramani Ramchandran, PhD, the Patrick J. and Margaret G. McMahon Professor of Obstetrics and Gynecology, vice chair for research in obstetrics and gynecology at MCW, and investigator with the Children’s Hospital of Wisconsin Research Institute, is the primary investigator of the project. He is also a member of the department of pediatrics, division of neonatology.

Researchers recently discovered a novel form of gene regulation in which RNA molecules that do not code for proteins directly regulate gene expression. Dr. Ramchandran, along with his team member Dr. Keguo Li, instructor of obstetrics and gynecology, identified this form of gene regulation in the Delta like 4 (Dll4) gene. Dll4 gene when over expressed specifically in vascular tissue or knocked out in mouse, show distinct vascular anomalies including arterial-venous fusions. Vascular anomalies are debilitating conditions affecting children, and adults, for which urgent therapy options are needed. In this study, the team of investigators will unravel the long non-coding RNA-mediated molecular mechanisms that regulate Dll4 gene expression during embryonic development, and investigate how this regulation is altered in select vascular anomaly patients. Co-investigators in this project include Lisa Cirillo, PhD, Qing Robert Miao, PhD, Shama Mirza, PhD, and Paula North, MD, PhD. Patricia Burrows, MD, also serves as a consultant on the project.

Knowledge gained in this study could potentially lead to new therapeutic mechanisms and targets for vascular anomaly.