In 2006, I was invited by the National Heart Lung and Blood Institute to help formulate a strategy for Systems Biology in pathologies of heart, lung and blood and this resulted in a “NHLBI Systems Biology” PA/RFA and I was one of the early awardees of a R33 grant to study cardiomyocyte differentiation using systems approaches. This project led to the development of the RNA seq method (described earlier) as well as the identification of small molecules (in the laboratory of co-Investigator Mercola) and micro RNA (jointly in our efforts) that promoted cardiomyocyte differentiation. This project also led me to investigations in oxidative stress in endothelial cells, where we have very detailed mechanisms associated with endothelial response (unpublished work, as yet). The latter motivated collaborations with Professors Shu Chien and John Shyy in launching a physiologically relevant research project on a systems biology study of shear stress response by the endothelium. We obtained two grants from NHLBI (jointly with Chien and Shyy) under the aegis of NHLBI Systems Biology initiative. Our initial work resulted in identification of differential regulation of response to pulsatile and oscillatory stress on endothelial cells by early signaling events and subsequent microRNA-based regulation of transcripts. This work was published in a few manuscripts. We are now embarking on a systematic time series “omics” study of endothelial response to differential stress and anticipate this will provide us with deep insights for identifying and treating vascular pathologies.