Karen Hirschi, PhD, and Gael Genet, PhD, Awarded $3 Million to Study the Role of Endothelial Cell Cycle Control

December 12, 2023 by

University of Virginia researchers Karen Hirschi, PhD (Left), Gael Genet, PhD.

Karen Hirschi, PhD (Left), Gael Genet, PhD

Karen Hirschi, PhD, Alumni Professor of Cell Biology, Director of the Developmental Genomics Center, Associate Director of the UVA MSTP, and member of the Robert M. Berne Cardiovascular Research Center, and Gael Genet, PhD, Research Assistant Professor in the Department of Cell Biology were awarded a $3 million, four-year NIH Multi-PI R01 grant to study the role in arterial-venous specification during development and in disease conditions.

The Hirschi lab focuses on understanding how blood vessels form during normal development in order to find new therapeutic strategies to promote healthy embryonic development, repair of injured tissues, and engineering of tissue replacements. Mature blood vascular networks require arterial vessels that deliver oxygen-rich blood to tissues and venous vessels that return oxygen-low blood to the heart. However, it is not well understood how endothelial cells that line all these blood vessels acquire different characteristics in arteries vs. veins that enable them to perform distinct functions within the blood circulatory network. This has created significant roadblocks for clinical therapies, tissue engineering and regenerative medicine.

Recently, the Hirschi lab found that endothelial cell cycle state is a critical regulator that enables arterial and venous specification, which was described in two publications (Fang et al, Nature Communications 2017; Chavkin et al. Nature Communications 2022). Ongoing studies by the group aim to identify novel key regulators of endothelial cell cycle control and arterial-venous specialization during vascular development. Insights gained from these studies will be applied to the treatment of vascular diseases associated with endothelial cell hyperproliferation, including tumor angiogenesis and vascular malformations, such as Hereditary Hemorrhagic Telangiectasia (HHT). Patients with HHT have genetic mutations that cause arteriovenous malformations (AVMs) that can be debilitating and even lethal; unfortunately, noninvasive treatments for such vascular malformations are limited. With the support of this grant, the Hirschi lab will use cutting edge experimental and computational approaches to investigate the clinical relevance of using FDA-approved cell cycle modulators for the treatment of HHT and other vascular malformations and pathologies. Working with clinical investigators at UVA and beyond, a major goal is to translate this work to clinical studies in human patients with vascular pathologies.

Read more about Dr. Hirschi’s lab and connect on Twitter: @HirschiLab

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