research

William Altemeier

Associate Professor of Medicine, Division Pulmonary and Critical Care
Affiliate Investigator, Fred Hutchinson Cancer Research Center

MD

Faculty Web Page

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


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