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Project

Functional assessment and therapeutic targeting of a novel aortopathy syndrome caused by resessive IPO8 mutations.

Thoracic aortic aneurysm (TAA) is an abnormal widening of the thoracic aorta caused by blood vessel wall weakness. TAAs entail a high risk for aortic rupture or dissection, commonly leading to sudden death. This dramatic event may leave family members of the deceased terrified and oblivious. To date, genetic defects in >30 genes have been linked with TAA, providing a molecular cause for about 30% of patients. Their identification and functional characterization have been key in acquiring our current aortopathy knowledge. Yet, the genetic and mechanistic picture for TAA is far from complete, hampering identification of predictive markers for aneurysm formation and development of therapies capable of stopping or reversing aneurysm formation. In search for novel TAA genes, the Antwerp Cardiogenetics research group most recently identified recessive truncating mutations in IPO8 as a novel cause of syndromic TAA. My PhD project builds on this exciting finding. More specifically, I aim to significantly improve our current TAA pathomechanistic insight and future TAA patient management by (1) investigating IPO8 as a novel syndromic TAA gene through characterization of an Ipo8 null mouse line, (2) elucidating the IPO8-related pathomechanisms using patient- and control-derived cell lines, and (3) identifying putative drug compounds for IPO8-related aortopathy using a cell-based matrix metalloproteinase inhibition assay.
Date:1 Jan 2019 →  31 Dec 2022
Keywords:AORTAPATHY
Disciplines:Vascular diseases