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Baraa Kwieder

BHF Cambridge Centre of Excellence PhD Student


Research Interests

Supervisor: Dr Amer Rana

Title: Directed programming of arterial endothelial cell identity, and the assembly of arteries through 3D co-culture for translational applications

Abstract: Blood vessels are divided into arterial and venous systems. For endothelial cells (ECs), these specific vascular identities are bestowed by a genetic programme, initiated during embryonic and foetal development, and reinforced by environmental factors, such as flow and shear stress, which enhance arterial identity. Later, in adults, the genetic programme is reactivated during regenerative processes following injury and reinforced by environmental factors to obtain arterial and venous identities during neo-vascularisation, but may also be impaired in disease states.

There is a clear need for easily accessible and defined endothelial cell (EC) populations for a number of translational medicine applications including disease modeling, identification of biomarkers, drug discovery, and cell replacement therapies. One possibility is to use endothelial progenitors, the most accessible being blood-outgrowth endothelial progenitors. These vascular endothelial cells are highly proliferative but have a limited self-renewal capacity. In addition, it is not clear if progenitor cells could mimic or replace all types of vascular endothelial cells.

Human pluripotent stem cells can be programmed to produce endothelial cells with an arterial identity, and these arterial ECs can be assembled into arteries through 3D co-culture with smooth muscle cells and cardiomyocytes for disease modeling.

My PhD project has three specific aims:

1. Transcriptomic and epigenomic characterisation of arterial and venous EC identity and responses in different environmental conditions.

2. Generation of arterial ECs from different embryonic origins from human pluripotent stem cells to mimic coronary and pulmonary arterial endothelial cells.

3. Functional characterisation of arterial ECs and three-dimensional co-cultures to generate arterial like structures.

Keywords

endothelial progenitor cells ; pluripotency ; stem cells ; regenerative medicine

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