Pulmonary Vascular Disease Program

Director: Dr. Steven Kawut »       kawut@mail.med.upenn.edu

About
The Pulmonary Vascular Disease Program is focused on understanding the mechanisms of a variety of diseases characterized by pulmonary vascular dysfunction and the subsequent effects on the right side of the heart. This program includes researchers and clinicians from various disciplines, including pulmonary, cardiology, pathology, developmental and cell biology, radiology, surgery, biostatistics, and genetics. Extensive experience in cellular physiology, cardiovascular function, electrophysiology, high-throughput genetics, epidemiology, biostatistics, clinical trials, and clinical care of patients with a variety of pulmonary vascular diseases and/or right heart failure enables the translation of research questions concerning health and disease into feasible studies.

Research Themes

Basic / Translational Research:
The basic and translational laboratories within this program unit provide an established infrastructure for studies of cellular function, myocardial physiology, animal models of right ventricular failure, transcriptional profiling, and molecular genetics. There are several research themes which form the backbone of the basic science program. One focus is the contribution of certain genes, such as Prx, to lung vasculogenesis in animal models. The role of Wnt-signaling and GATA and Fox transcription factors in the lung is an area of particular interest. BMPRII-controlled signaling mediated by tenascin-C in health and pulmonary arterial hypertension are other areas of active investigation in the program.

Clinical Research:
This unit has a strong interest in clinical research, as well. Investigators in the program lead the first NIH-sponsored, multicenter randomized clinical trial in pulmonary arterial hypertension (ASA-STAT) with the established infrastructure to perform other selected industry-sponsored trials. A second theme in the clinical research component of the program is the study of right ventricular function. MESA-RV is a NIH-sponsored study of right ventricular function in a cohort of several thousand individuals without clinical cardiovascular disease.

The clinical and genetic determinants of pulmonary vascular dysfunction syndromes in patients with advanced liver disease and portal hypertension comprise another research area. Quality-of-life and cognitive function studies in patients with pulmonary arterial hypertension and novel approaches to cardiac imaging are being undertaken by program members. Investigators from this program are members of the ongoing REVEAL Registry, designed to study the current practices in diagnosis and treatment of pulmonary arterial hypertension in the U.S.

Program members also study the contribution of the pulmonary vasculature to acute lung injury. Two NIH grants support a prospective multicenter cohort study of primary graft dysfunction after lung transplantation (Lung Transplant Outcomes Group).

Cell Core

The Cardiovascular Medical Research and Education Fund supports a multicenter study of pulmonary arterial hypertension and established its Cell Core at Penn, directed by Peter Lloyd Jones, Ph.D and Darren Taichman, MD, Ph.D. The responsibilities of this Core include the acquisition, isolation, and phenotyping of control and pulmonary arterial hypertension lung vascular and circulating cells and fluids. The immortalization and distribution of these biologic materials to the multicenter network make this Core a key element for future studies in pulmonary arterial hypertension.

Clinical Program

Many of the research projects depend on the seamless integration of investigators with the very active clinical program which has existed at the University of Pennsylvania for more than 25 years, originally initiated by Alfred P. Fishman, MD. One of the largest of its kind in the United States, the clinical Pulmonary Vascular Disease Program is based at the Hospital of the University of Pennsylvania (headed by Paul Forfia, MD, Clinical Co-Director), the Penn Presbyterian Medical Center (headed by Harold Palevsky, MD, Clinical Co-Director), and the Children's Hospital of Philadelphia (headed by Brian Hanna, MD, PhD). The clinical program evaluates patients with all types of pulmonary vascular disorders, including pulmonary arterial hypertension, chronic thromboembolic disease, hepatopulmonary syndrome, and pulmonary hypertension due to left-sided heart disease.

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