Madeline McNamara

Supervisor: Dr Sanjay Sinha

Co-supervisor: Prof Shoumo Bhattacharya

Title: Development of new therapies for Marfan's syndrome using an in vitro human iPSC disease model

Abstract: Marfan’s syndrome (MFS) is a connective tissue disorder with pleiotropic manifestations including severe cardiovascular complications, such as aortic aneurysms and aortic rupture. Abnormal widening of aortic structures is caused by mutations in the extracellular matrix structural component, fibrillin-1. As a result, MFS patients display impairment in fibrillin-1 deposition, increased extracellular matrix degradation and excessive signalling by the transforming growth factor beta (TGF-β) pathway.

In this project, we will be using our human induced pluripotent stem cell (hiPSC)-derived in vitro model system for MFS to develop new therapies aimed at ameliorating the disease phenotype. Our approaches include correcting the mutations in FBN1, the gene coding for fibrillin-1, identifying targets downstream of dysfunctional FBN1 implicated in MFS pathogenesis, and transitioning our novel therapies into more physiologically relevant in vitro culture and in vivo model systems.