To rigorously test mechanistic hypotheses regarding disease progression with all the complexity of a physiological system but without age, sex, nutrition, socioeconomic, body habitus, and genetic variability, pre-clinical studies are often required. We are expert with both large and small animal models, including inbred and genetically engineered strains. In these approaches, we also use advanced imaging and measurement technologies as well as sophisticated data analysis. We also develop novel experimental and surgical techniques to create disease or dysfunction that we hypothesize is critical to disease. Currently, we are using large animal models to determine the drivers of right ventricular failure secondary to left heart failure and the mechanisms by which acute thromboembolic pulmonary hypertension transitions to chronic thromboembolic pulmonary hypertension; we are using small animal models to study molecular mechanisms of pulmonary hypertension development secondary to left heart failure, the role of estrogen in right ventricular dysfunction and failure, and the multi-scale mechanisms of right ventricular failure due to pressure overload. We have also used pre-clinical research approaches to investigate sickle cell anemia and pre-term birth.