Internship: The role of adrenomedullin in angiogenesis

Background 

Diabetic retinopathy (DR), a major complication of diabetes, is the leading cause of vision loss in adults in the developed world. The disease disrupts the retinal neurovascular unit, leading to vascular hyperpermeability, edema, and pathological angiogenesis as it progresses—ultimately resulting in visual impairment and blindness. 

 Clinical studies have detected elevated levels of adrenomedullin (ADM), a vasoactive peptide, in the vitreous of DR patients, suggesting its involvement in disease progression. ADM plays key roles in vascular development, vasodilation, angiogenesis, and endothelial barrier stabilization. However, the precise mechanisms by which ADM regulates angiogenesis remain unclear. A deeper understanding of these processes could reveal novel therapeutic targets for DR. 

 Project Aims 

1) Investigate how ADM regulates angiogenesis in endothelial cells. 2) Determine whether ADM influences: endothelial cell migration, lumen formation and sprout morphology

Methods 

Using primary endothelial cells, you will employ the following assays: 

- 2D scratch assay → measures cell migration 

- 3D spheroid assay → measures sprout length and number 

- 3D OrganoPlate sprouting assay → Analyzes lumen formation and sprout morphology in a microphysiological vessel-on-a-chip system 

The assays will be done using primary endothelial cells using knockdown of ADM with siRNA. This project will provide hands-on experience in cell culture, immunofluorescence and live cell imaging, and quantitative analysis of angiogenesis.

Interested? Send your CV and a short motivation (in Dutch or English) to Ingeborg Klaassen: i.klaassen @ amsterdamumc.nl.