White Lab

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

Associate Professor - Department of Medicine, Pulmonary Diseases and Critical Care - Primary Jim White
Associate Professor - Department of Pharmacology and Physiology
1997 | MD | Medicine | Univ Pittsburgh Sch Medicine
1996 | PhD | Neuroscience | Univ Pittsburgh Sch Medicine
1990 | BS | Arts & Sciences | Ohio State University

Research Overview

The overall goal of my laboratory is to understand the pathobiology which causes vascular remodeling in severe human pulmonary hypertension. Severe pulmonary arterial hypertension (PAH) occurs in idiopathic form and is also observed in diseases as diverse as scleroderma, HIV infection, and cirrhosis. In advanced human disease of many etiologies, endothelial proliferation and medial hypertrophy ultimately obliterate the lumen.  Altered cellular migration, excess proliferation, insufficient apoptosis, vascular wall inflammation, and platelet activation all make contributions to disease progression.

Our main experimental approach to the study of PAH is a rat model that recapitulates the histopathology, severe hemodynamic alterations, and right ventricular heart failure seen in advanced human disease. This rat model employs right pneumonectomy in young rats with endothelial injury (monocrotaline) to cause rapidly progressive pulmonary hypertension over 4 weeks.  We use modern telemetry catheters from Millar/TR to assess the development of PH on a daily basis, and we assess the pulmonary circulation in a quantitative fashion at the time of sacrifice by micro CT (see Figure).  Ultimately, we will be studying serum mediators and tissue gene expression. More basic experiments with smooth muscle and endothelial cell cultures are helping us to understand how altered cellular migration plays a role in the vascular pathology of PH.


Currently, there are two molecules of interest in the laboratory, tissue factor and thrombin. Tissue factor (TF) is a transmembrane glycoprotein that initiates the coagulation cascade and may also participate in angiogenesis; its regulation is responsive to inflammation and mechanical forces. Despite the known occurrence of in situ thrombosis and several reports linking platelet activation to the etiology of severe disease, TF had not been studied in PAH before our report in 2007. TF is not present in the normal media; it is abnormally expressed in both the vascular smooth muscle and the endothelium of pulmonary arterioles in patients with severe PAH. We are currently testing the hypothesis that tissue factor (TF) expression is essential in the propagation of the endothelial and smooth muscle remodeling. We are using a peptide isolated from the deer tick called Ixolaris to inhibit TF activity once animals have developed PH; this approach should allow us to understand whether a TF inhibitor might be a useful treatment option for human patients with PAH.

Thrombin has not been a major focus of most laboratories studying pulmonary hypertension despite the fact that warfarin anti-coagulation is accepted as a mainstay of therapy.  We have identified a unique role for thrombin in promoting the migration of microvascular endothelial cells isolated from the pulmonary circulation.  These cells are uniquely resistant to migration stimulated by most agonists (i.e., ET-1, Ang-2, SP-1), and thrombin only stimulates migration on a fibronectin-rich matrix.  The thrombin/FN stimulation results in a prolonged, intense calcium transient which stimulates calpain cleavage of talin; we believe that this signaling is relevant to the migration we have studied.  There are a number of potential therapeutic strategies that we might propose based on this work of David Meoli, a recently graduated MD/PhD student.

Deb Haight is my technician.  Former lab members include Dara Kallop, Bob Swarthout, and a pulmonary fellow, Jake Lyons.  Our work has been supported by the Parker B. Francis Foundation and the American Heart Association.White Lab Figure

Recent Publications

  1. Inhaled treprostinil sodium for the treatment of pulmonary arterial hypertension.
    Ferrantino M, White RJ., Expert Opin Pharmacother. 2011 Nov;12(16):2583-93. Review.
  2. Neonatal hyperoxia causes pulmonary vascular disease and shortens life span in aging mice., Yee M, White RJ, Awad HA, Bates WA, McGrath-Morrow SA, O'Reilly MA.
    Am J Pathol. 2011 Jun;178(6):2601-10. Epub 2011 May 6.
  3. Endothelin-1 induces pulmonary but not aortic smooth muscle cell migration by activating ERK1/2 MAP kinase. Meoli DF, White RJ. Can J Physiol Pharmacol. 2010 Aug;88(8):830-9.
  4. Thrombin induces fibronectin-specific migration of pulmonary microvascular endothelial cells: requirement of calcium/calmodulin-dependent protein kinase II. Meoli DF, White RJ.
    Am J Physiol Lung Cell Mol Physiol. 2009 Oct;297(4):L706-14. Epub 2009 Jul 31.
  5. G-protein-coupled receptor kinase interacting protein-1 is required for pulmonary vascular development. Pang J, Hoefen R, Pryhuber GS, Wang J, Yin G, White RJ, Xu X, O'Dell MR, Mohan A, Michaloski H, Massett MP, Yan C, Berk BC. Circulation. 2009 Mar 24;119(11):1524-32. Epub 2009 Mar 9.

More papers: PubMed

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R. James White, M.D., Ph.D
University of Rochester
School of Medicine and Dentistry
601 Elmwood Ave, Box 692
Rochester, New York 14642
Telephone: (585) 486-0147

Lab Members

Deborah Haight

Deborah Haight

Laboratory Technician

Serban Staicu

Serban Staicu

Postdoctoral Associate