The goal of our study is to develop novel therapeutic strategies for various diseases by revealing the fundamental biologic principles with strong focus on the vasculature. Especially, we are interested in cell polarity regulators and has revealed their functions in vascular health and diseases. Especially, we have shown that atypical PKC (aPKC) is the critical factor for angiosarcoma patient prognosis by controlling FoxO and c-Myc transcription factors. Furthermore, we have investigated the role of PAR-3 in response to blood flow and in vascular inflammation. Our findings will represent a very substantial conceptual advancement with potential readily translatable results for clinical usage of endothelial related diseases.