"This application promises to provide new treatment options for cancer and cardiovascular diseases that are the leading causes of morbidity and mortality in the western world. Current cardiovascular and cancer therapies are often insufficient, unsuccessful or not suitable for all patients. Inhibition of angiogenesis is already used in the clinics, but with limited success. On the other hand, stimulation of the growth of blood vessels, angiogenesis, and of arteriogenesis, the growth of (collateral) arteries, has been unsuccessfully tried for the treatment of tissue ischemia. The aim of this research plan is to reveal new disease-related functions of endothelial growth factors and their signal transduction in cancer and cardiovascular disease and to establish preclinical models of effective therapy based on new knowledge of the biology of vascular endothelial growth factors (VEGFs), angiopoietins (Ang), angiogenesis and lymphangiogenesis. We will embark on new studies based on our novel discoveries on the crosstalk between endothelial growth factor pathways in tumor angiogenesis, the involvement of lymphatic vessels in the development of obesity and associated inflammation, and on the striking effects of VEGF-B on cardiac muscle and vessels. We will develop molecular genetic and iPS cell derived models, and use functional genomics, proteomics and metabolomics, viral gene delivery and blocking reagents from human antibody libraries for our studies that should be of high priority in basic science and medicine. My laboratory is uniquely suited and networked for new discoveries to advance therapies for both cancer and cardiovascular diseases. Some of our work has already been translated to clinical development and we aim to provide additional drug candidates in this project."