in silico

In Silico Studies

Computer models represent a distillation and formalization of our working hypotheses regarding cardiopulmonary structure-function-regulation relationships. This in silico approach facilitates a rigorous cycle of hypothesis testing (quantitative comparison of model predictions to experimental observations), hypothesis refinement (redesign and reformulation of models in light of mis-matches between predictions and data), and model-guided experimental design. We are currently using in silico approaches to study the mechanobiological mechanisms of transition from isolated post-capillary pulmonary hypertension to combined pre/post capillary pulmonary hypertension and the multi-scale mechanisms of right ventricular failure.

in vitro 2

In Vitro Studies

Often, we test hypotheses regarding mechanobiological mechanisms of disease progression in the absence of an intact physiological system. These in vitro or cell culture studies yield insights into the effects of mechanical stimuli, such as shear stress and cyclic stretch, on endothelial cell biology. This approach also gives exquisite control over the cell chemical environment, source of cells, and allows imaging and cytokine readouts coincident with mechanical stimulation. We are currently using in vitro approaches to study the mechanobiological mechanisms of transition from isolated post-capillary pulmonary hypertension to combined pre/post capillary pulmonary hypertension.

Preclinical Mouse image

Pre-Clinical Studies

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.

clinical studies image

Clinical Studies

In collaboration with cardiologists, pulmonary medicine and critical care physicians, radiologists, medical physicists, surgeons, and pediatricians, we are advancing knowledge of cardiopulmonary disease progression by enrolling volunteers in retrospective and prospective studies that use advanced imaging and measurement technologies as well as sophisticated data analysis. We frequently used exercise or inhaled gasses to explore the response of the cardiopulmonary system to acute stress. In our current clinical research studies, we are studying the impact of preterm birth, pulmonary arterial hypertension, pulmonary venous hypertension, and left heart failure on cardiopulmonary structure and function.