Endothelial invasion in 3D matrices

The mechanism through which primary human endothelial cells invade into 3D matrices is being studied. The model used mimics angiogenesis, or the process of new blood vessel formation from existing structures (see Figure 1)

Angiogenesis is critical for successful pregnancy and abnormally stimulated during tumor growth, rheumatoid arthritis and blinding eye diseases such as diabetic retinopathy, retinopathy of prematurity and macular degeneration.

Intracellular molecular signals that are responsible for endothelial invasion responses are being investigated; along with important surface molecules include membrane-associated matrix metalloproteinases and integrins. We are utilizing pharmacological, gene knockdown, gene expression and protein localization studies to confirm the involvement of all molecules identified in preliminary screening experiments.

Extracellular matrix biology

Collaborative studies with Dr. Alvin Yeh's laboratory (Texas A&M University, Department of Biomedical Engineering) have revealed details about communication between invading endothelial cells and their surrounding 3D collagen matrix (see Figure 2). In these studies, two photon fluroescence was used to detect fluorescently-labeled endothelial cells as well as the surrounding collagen matrix using second harmonic generation (SHG). These studies combined with biochemical analyses are expected to provide further insight into molecular signals that regulate endothelial cell interactions with the extracellular fibrous collagen matrix as they form multicellular sprouting structures that contain lumens.