R. James White, III., M.D., Ph.D.

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My professional focus is to understand the vascular biology of pulmonary arterial hypertension (PAH) and to apply the best science in the care of patients. The lab uses a rat model of severe PAH (pneumonectomy and monocrotaline) and they measure the effects of PAH on exercise tolerance, hemodynamics, and angiography. They are testing novel small molecules that might be useful in treating patients with this devastating disease. I am currently treating ~130 patients for PAH with 30 patients on Remodulin or Flolan. We are actively enrolling in national clinical trials for PAH.

The overall goal of my research 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 than those in previous reports with a more severe phenotype; we have presented the first report of plexiform lesions. We have developed a novel treadmill exercise test to monitor disease progression, and we are also utilizing a three dimensional angiography technique to assess for vascular pruning. 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 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 M.D. Ph.D. student in my laboratory, David Meoli.

I direct the clinical program in pulmonary hypertension, and we exclusively follow patients with pulmonary arterial hypertension. Our operation is ably managed by Karen Frutiger, RN, who enrolls patients in clinical trials and provides triage assistance for the day-to-day care of all of our patients. We were a top enrolling site for the now complete oral tadalafil trial (PHIRST); we were one of the first sites enrolling patients in oral Remodulin (FREEDOM), and we are actively participating in the REVEAL Registry. Jake Lyons, a senior pulmonary fellow, is a named co-investigator on all of our clinical trial work, and fellows have an opportunity to spend time learning about PAH. We are also doing industry sponsored, investigator-initiated clinical trial work studying a novel use of iloprost in the postoperative setting.

Current Appointments

• Assistant Professor - Department of Medicine (SMD)

Lab Description

The overall goal of my laboratory is to understand the vascular biology which causes severe pulmonary arterial hypertension.

Lab Website

http://www.urmc.rochester.edu/research/white-lab.cfm