research
William Altemeier
Associate Professor of Medicine, Division Pulmonary and Critical Care
Affiliate Investigator, Fred Hutchinson Cancer Research Center
MD
Research Focus
Our laboratory focuses on transcriptional regulation during acute lung injury. We are particularly interested in how mechanical ventilation/stretch modulates the transcriptional response to Toll-like receptor signaling and in the role of endoplasmic stress response pathways contribute to the pathogenesis of acute lung injury and resolution. Our laboratory utilizes both cellular and intact mouse models and combines physiological assessments of lung injury with cellular and molecular mechanistic studies. Models of lung injury currently active in our lab include mechanical ventilation with or without specific TLR-ligands or bacterial or viral infections, hyperoxia-induced lung injury, ischemia-reperfusion lung injury, and bleomycin-induced lung injury. These models allow investigation of different pathways on acute and sub-acute injury and resolution of injury.
Relevant Publications
Altemeier WA, Robertson HT, McKinney SE, Glenny RW. Pulmonary embolization causes hypoxemia by redistributing blood flow without changing ventilation. J Appl Physiol 1998; 85(6): 2337-2343. PMID9843561
Altemeier WA, McKinney SE, Glenny RW. Fractal nature of regional ventilation distribution. J Appl Physiol 2000; 88(5): 1551-1557. PMID10797111
Altemeier WA, Matute-Bello G, Frevert CW, Kawata Y, Kajikawa O, Martin TR, Glenny RW. Mechanical ventilation with moderate tidal volumes synergistically increases lung cytokine response to systemic endotoxin. Am J Physiol Lung Cell Mol Physiol 2004; 287:L533-L542. PMID15145786
Sinclair SE, Altemeier WA, Matute-Bello G, Chi E. Augmented lung injury due to interaction between hyperoxia and mechanical ventilation. Crit Care Med 2004; 32(12): 2497-2501. PMID15599157
Altemeier WA, Matute-Bello G, Gharib SA, Glenny RW, Martin TR, Liles WC. Modulation of LPS-induced gene transcription and promotion of lung injury by mechanical ventilation. J Immunol 2005; 175(5): 3369-3376. PMID16116230
Gharib SA, Liles WC, Matute-Bello G, Glenny RW, Martin TR, Altemeier WA. Computational Identification of Key Biological Modules & Transcription Factors in Acute Lung Injury. Am J Respir Crit Care Med 2006; 173(6): 653-658. PMID16387799
Dhanireddy S, Altemeier WA, Matute-Bello G, O’Mahony S, Glenny RW, Martin TR, Liles WC. Mechanical ventilation induces inflammation, lung injury, and extra-pulmonary organ dysfunction in experimental pneumonia. Lab Invest 2006; 86(8): 790-799. PMID16855596
Altemeier WA, Zhu X, Berrington WR, Harlan JM, Liles, WC. Fas (CD95) induces macrophage pro-inflammatory chemokine production via a MyD88-dependent, caspase-independent pathway. J Leuk Biol 2007; 82(3): 721-8. PMID17576821
Sinclair SE, Chi E, Lin HI, Altemeier WA. Positive end-expiratory pressure alters the severity and spatial heterogeneity of ventilator-induced lung injury: An argument for cyclical airway collapse. J Crit Care 2009; 24: 206-211. PMID19327294
Gharib SA, Liles WC, Klaff LS, Altemeier WA. Non-injurious mechanical ventilation activates a pro-inflammatory transcriptional program in the lung. Physiol Gen 2009; 37(3) 239-248. PMID19276240
Active Funding
Funding Source |
Project Title |
Investigator Role |
Funding Dates |
NHLBI |
Mechanisms of innate immune response modulation by mechanical ventilation |
PI |
12/1/2008-11/30/2013 |
NHLBI |
The alveolar epithelium in lung injury and repair |
Co-investigator |
7/1/2006-6/30/2011 |
Current Mentees
Name |
Degree |
Project |
Lindy Klaff |
MD |
Role of integri-matrix activation in stretch-induced gene transcription |
Joel Nelson |
PhD |
Role of MAP kinase activation in stretch-induced gene transcription |
Past Mentees
Name |
Degree |
Current title |
Location |
Shireesha Dhanireddy |
MD |
Assistant Professor |
University of Washington, Seattle, WA -- Harborview Medical Center |
Ana Villagra |
MD |
Staff Physician |
Hospital de Sabadell, Sabadell, Spain |
Carrie Chun |
MD |
Staff Physician |
Scripps Health, San Diego, CA |