Department of Molecular and Cellular Medicine
142 Reynolds Medical Building
College Station, Texas 77843
Education and Post-Graduate Training
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.
Kang H, KJ Bayless, R Kaunas. (2008). Fluid shear stress modulates endothelial cell invasion into three-dimensional collagen matrices. Am. J. Physiol. Heart Circ. Physiol. 295, H2087-H2097.
Su SC, EA Mendoza, HI Kwak, and KJ Bayless. (2008). Molecular profile of endothelial invasion of three-dimensional collagen matrices: insights into angiogenic sprout induction in wound healing. Am. J. Physiol. Cell Physiol. 295, C1215-C1229.
Lee PF, AT Yeh, KJ Bayless. (2009) Nonlinear optical microscopy reveals invading endothelial cells anisotropically alter three-dimensional collagen matrices. Exp. Cell Res. 315, 396-410.
Kwak HI, EA Mendoza, KJ Bayless. (2009). ADAM17 co-purifies with TIMP-3 and modulates endothelial invasion responses in three-dimensional collagen matrices. Matrix Biol. 28, 470-479.
Bayless KJ, HI Kwak, SC Su. (2009). Investigating endothelial invasion and sprouting behavior in three-dimensional collagen matrices. Nature Protocols 4, 1888-1898.
SC Su, SA Maxwell, KJ Bayless. (2010). Annexin 2 regulates endothelial morphogenesis by controlling AKT activation and junctional integrity. J. Biol. Chem. 285, 40624-40634.
Maxwell SA, EM Cherry, and KJ Bayless. (2011). Akt, 14-3-3ζ, and vimentin mediate a drug-resistant invasive phenotype in diffuse large B-cell lymphoma. Leuk Lymphoma. 52(5):849-64.
Bayless KJ, and GA Johnson. (2011). Role of the cytoskeleton in formation and maintenance of angiogenic sprouts. Journal of Vascular Research. 48, 369-385.
Kaunas R, H Kang and KJ Bayless. (2011). Synergistic regulation of angiogenic sprouting by biochemical factors and wall shear stress. Cellular and Molecular Bioengineering, 4(4):547-559.
Kang H, HI Kwak, RR Kaunas, and KJ Bayless. (2011). Fluid Shear Stress and Sphingosine 1-Phosphate Activate Calpain to Promote MT1-MMP Membrane Translocation and Endothelial Invasion in Collagen Matrices. J. Biol. Chem., 286(49):42017-26.
Kwak H-I, H Kang, EA Mendoza, SC Su, SA Maxwell, and KJ Bayless. (2012). Calpain-mediated vimentin cleavage occurs upstream of MT1-MMP membrane translocation to facilitate endothelial sprout initiation. Angiogenesis, 15(2):287-303.
Su SC, Bayless KJ. (2012). Utilizing sphingosine-1-phosphate to stimulate sprouting angiogenesis. Methods Mol Biol. 874:201-13.
Lee DW, Ramakrishnan D, Valenta J, Parney IF, Bayless KJ, Sitcheran R. (2013). The NF-κB RelB protein is an oncogenic driver of mesenchymal glioma. PLoS One. 8(2):e57489.
Lee PF, Bai Y, Smith RL, Bayless KJ, Yeh AT. (2013). Angiogenic responses are enhanced in mechanically and microscopically characterized, microbial transglutaminase crosslinked collagen matrices with increased stiffness. Acta Biomater. 2013 9(7):7178-90.
Patterson JL, Abbey CA, Bayless KJ, Bondos SE. (2013) Materials composed of the Drosophila melanogaster protein ultrabithorax are cytocompatible. J Biomed Mater Res A. 2013 Apr 18. doi: 10.1002/jbm.a.34675. [Epub ahead of print].