Eric S. White, M.D.
Assistant Professor,
Department of Internal Medicine

docew@umich.edu

Research interests:

Extracellular matrix/integrin signaling
Fibronectins
PTEN tumor suppressor
Fibroblast biology
Sarcoidosis immunology

Current Research Activity:

The White Lab has a number of projects involving inflammation and wound repair in the lung. One project focuses on the development and manifestation of granulomatous inflammation in the lungs, which mimics the disease sarcoidosis. Currently in our lab, we are establishing a model of granulomatous inflammation to the normal commensal bacteria Propionibacterium acnes. This bacteria is a normal inhabitant of the skin of the humans and mice but is implicated in the pathogenesis of sarcoidosis in a subset of patients.  Recent evidence suggests that this bacterium is normally found in small numbers in the lungs and draining lymph nodes of humans and mice.  A mouse model has recently been described in which animals are sensitized to P. acnes and these mice then spontaneously develop sarcoid-like disease in the lungs and systemically.  This disease can be transferred by the CD4 positive T cell subset to naïve mice.  Thus, the hypothesis of this project is that a loss of tolerance to this commensal bacteria can lead to the development of pulmonary granulomatous disease. Using methodologies that are well established in our collaborator's lab (Gary Huffnagle), we will be looking at the development of regulatory T cell networks and Th17 responses in a murine model of P. acnes pulmonary granulomatous disease. We will compare these results with data that our laboratory is obtaining about these responses in healthy human and sarcoidosis patients.  

A second project involves the role of the extracellular matrix protein fibronectin in wound repair. We and others have previously found that splice variations within the fibronectin molecule are integral to wound healing in the lung. Current experimentation is designed to delineate the role of a specific isoform (termed EDA fibronectin) in mitigating lung inflammation and promoting fibrosis. We are actively investigating the roles of known EDA-binding integrins in mediating these responses in the hopes of devising clinical trials for patients with fibrotic lung disease.

Representative Publications

ES White, VJ Thannickal, SL Carskadon, EG Dickie, DL Livant, S Markwart , GB Toews, and DA Arenberg. Integrin a 4 b 1 regulates migration across basement membranes by lung fibroblasts: A role for phosphatase and tensin homologue deleted on chromosome ten . 2003. Am J Resp Crit Care Med. 168: 436-442.

ES White, RG Atrasz, EG Dickie, DM Aronoff, V Stambolic, TW Mak, BB Moore, and M Peters-Golden. Prostaglandin E2 inhibits fibroblast migration by EP2 receptor-mediated increase in PTEN activity . 2005. Am J Resp Cell Mol Biol. 32:135-141.

ES White, RG Atrasz, B Hu. SH Phan, V Stambolic, TW Mak, CM Hogaboam, KR Flaherty, FJ Martinez, CD Kontos, and GB Toews. Negative regulation of myofibroblast differentiation by PTEN. 2006. Am J Resp Crit Care Med. 173: 112-121.

RS Nho, H Xia, D Diebold, J Kahm, J Kleidon, ES White, and CA Henke. PTEN regulates fibroblast elimination during collagen matrix contraction. 2006. J Biol Chem . 281: 33291-33301.

ES White, DA Zisman, DT Keena, and JP Lynch, III. Corticosteroid therapy for sarcoidosis. 2006. In Sarcoidosis , R.P. Baughman, Ed. Lung Biology in Health and Disease Series, vol. 210. Claude Lenfant, Exec. Ed. Marcel Dekker. New York , NY . pp. 689-716.

JP Lynch III, YL Ma, MN Koss, and ES White. Pulmonary Sarcoidosis. 2007. Sem Resp Crit Care Med. 28(1): 53-74.