In adults, endothelial cells, as opposed to skin, liver or intestinal epithelium, display low turn-over and limited ability to regenerate. Bone marrow cells have the ability to regenerate quickly. It has been shown that bone marrow is a reservoir of both hematopoietic and non-hematopoietic progenitor cells. For example, the ability of bone marrow derived cells to engraft as alveolar type 1 epithelial cells and as bronchial epithelial cells has been shown. Bone marrow has been used as a source of EPC for experimental treatments for cardiac and limb ischemia. Currently, we are isolating and purifying a sub-population of cells from bone marrow, and providing them with specific matrix and biochemical cues to dictate the expansion of EPCs ex-vivo. The questions we are asking has direct relevance to cell-based therapies for regenerative and reparative medicine.

Figure 1. Endothelial cells were immunostained with anti-von Willebrand
factor (green) mAb, TRITC-phalloidin (red), and DAPI (nucleus, blue).

Angiogenesis, or the remodeling of pre-existing quiescent blood vessel, is critical for embryonic development, wound healing, and various pathophysiological conditions including wound healing, vascular permeability, blood brain barrier function, angiogenesis, diabetic retinopathy, atherosclerosis, psoriasis, and tumor progression. Identification of the molecules and signaling pathways associated with the activation of endothelial cells could help uncover their role in the above mentioned pathophysiological processes. We discovered phosphatidic acid phosphatase-2b (PAP2b), also known as Lipid phosphate phosphohydrolase-3 (LPP3) in a functional assay of angiogenesis. The PAP2b protein is expressed by activated endothelial cells, exhibits a cell adhesion sequence, and dephosphorylates phosphatidic acid phosphate (PAP) nto diacylglycerol and phosphate, that has been implicated in cell signaling and lipid metabolism. Conventional deletion of Lpp3 gene is incompatible with life, as the embryos die at E7.5 days due to defective vasculature. Currently, we are testing the hypothesis that during angiogenesis PAP2b plays a key role in the formation and organization of adhesion structures connecting endothelial cells. Our experimental approaches include both "loss-of-function" and "gain-of-function" assays. We anticipate that our studies is likely to further our understanding of the role of endothelial PAP2b in angiogenesis.

Lab Members

Representative Publications

• Thakker GD and Wary KK. Integrin signaling in the pathobiology of vascular smooth muscle cells. 2006; Vascular Dis Prev. Review (in press)


• Wary KK. Molecular targets for anti-angiogenic therapy. Curr Opin Mol Ther. 2004; 6: 54-70. Review.


• Humtsoe JO, Feng S, Thakker GD, Yang J, Hong J, Wary KK. Regulation of cell-cell interactions by phosphatidic acid phosphatase-2b/VCIP. EMBO J. 2003; 22: 1539-1554.


• Wary KK, Mariotti A, Zurzolo C, Giancotti FG. A requirement for caveolin-1 and associated kinase Fyn in integrin signaling and anchorage-dependent cell growth. Cell. 1998; 94: 625-634.


• Wary KK, Mainiero F, Isakoff SJ, Marcantonio EE, Giancotti FG. The adaptor protein Shc couples a class of integrins to the control of cell cycle progression. Cell. 1996; 87: 733-743.