Grant: Foundation Grant

One of the major ways that normal cells can get sick is when their fuel's supply to demand balance is disrupted. The "power plants" that regulate the handling of fuel (oxygen, sugars, lipids) in the cell are organelles called mitochondria. We now know that there is mitochondrial dysfunction in many common diseases (like diabetes or cancer for example) but also in more rare but deadly diseases like pulmonary hypertension, where the blood vessels of the lungs are gradually destroyed leading to shortness of breath and premature death. There are no effective treatments that prolong the life of patients with pulmonary hypertension, similar to cancer. Here we propose to perform studies in order to understand better how the mitochondria dysfunction leads to pulmonary hypertension. We have drugs that can normalize mitochondrial function and we will test to see whether they may become therapies for pulmonary hypertension. We will use animal models and human organs that we receive at the time of transplant surgery. We also plan to test some of these drugs to actual patients in order to answer the critical questions that exist before testing them in large groups of patients to prove that they help without harm. The breadth and depth of our work provides a superb training environment in which to train future doctors and scientists to discover novel therapies for deadly human diseases. Our previous success in this field of research and the strong support from our institution and our collaborators make us confident that we will succeed to actually improve the lives of patients in addition to advancing our scientific knowledge.