The overall goal of my clinical research and bench laboratory is to provide better care to patients with a rare disease of the lung blood vessels, pulmonary arterial hypertension (PAH). We provide care for patients from all over New York and central PA, and we use the full complement of approved PAH therapies. We also contribute actively to clinical research in hopes of better therapies with drugs that are already available. In my laboratory, we do experiments in animals and cells in an attempt to discover entirely new ways to treat this deadly disease.
The University of Rochester is the regional referral center for patients with echo estimated pulmonary hypertension. We take care of ~170 patients with WHO Group 1 classified Pulmonary Arterial Hypertension. I was a lead enroller and study author in the Phase III pivotal trial for tadalafil, and we continue to make significant contributions to the development of oral treprostinil (Remodulin). We are actively participating in the Reveal registry. We use subcutaneous treprostinil (about 50 patients), inhaled iloprost, bosentan, ambrisentan, tadalafil and sildenafil in combinations best tailored to a particular patients needs. We provide a strong link to San Diego for our patients with chronic thromboembolic pulmonary hypertension.
The overall goal of my bench laboratory is to understand the vascular biology which causes severe pulmonary arterial hypertension. Our main approach is with a rat model that recapitulates the histopathology, severe hemodynamic alterations, and right ventricular heart failure seen in advanced human disease. This rat model employs pneumonectomy (promotes contralateral lung growth) and endothelial injury (monocrotaline) to cause lethal pulmonary hypertension in about 4 weeks. Our animals die earlier with a more severe phenotype, and we have presented the first report of plexiform lesions. We have developed a novel CT angiography to assess for vascular pruning during disease progression, and we are also utilizing invasive techniques to measure pressure and cardiac output in awake, behaving animals. We hypothesize that tissue factor (the membrane bound glycoprotein which initiates coagulation) is an important contributor to disease progression, and we are actively testing small molecule inhibitors of tissue factor and thrombin as novel therapies in this devastating disease.
A second line of investigation seeks to define the role of thrombin and the PAR1 receptor in PH. In endothelial cells isolated from the rat pulmonary microvasculature, PAR1 activation promotes migration, wound closure, and tube formation in in vitro angiogenesis assays. The migratory activity is dependent on the matrix (fibronectin or collagen) and the microvascular endothelial cells behave differently than those derived from the proximal pulmonary artery. We hypothesize that plexiform lesions result from exuberant proliferation after these cells migrate to sites of injury rich in a fibronectin matrix. This is the work of the recently graduated M.D. Ph.D. student in my laboratory, David Meoli.
|Parker B. Francis Fellowship in Pulmonary Biology, Francis Family Foundation
||2005 - 2007
|Buswell Fellowship, Department of Medicine, University of Rochester SMD
||2003 - 2005
|NIH Training Grant Multi-Disciplinary Training & Pulmonary Research, University of Rochester SMD
||2001 - 2004
|Alpha Omega Alpha, University of Pittsburgh
|NIH Medical Scientist Training Program, University of Pittsburgh
||1990 - 1997
|Phi Beta Kappa, Ohio State University