Welcome to the Iowa Inflammation Program
Division of Critical Care
1988 - B.S., Zoology, Duke University
1992 - M.D., Medicine, Vanderbilt University
1995 - Resident, Pediatrics, Vanderbilt University
1998 - Fellow, Critical Care, Vanderbilt University
Brieanna Hilkin, BS, RA I
Jessica Hook, BS, MS RA II
The Moreland laboratory shares joint space and numerous collaborations with the Volk laboratory. The primary focus of our laboratory is to understand the role of the NADPH oxidase in intracellular signaling in intracellular signaling in neutrophils. We are interested in oxidant signaling both under resting and stimulated conditions, specifically in response to both TNF-α and endotoxin as might occur during Gram-negative sepsis. We are exploring the role of the anion transporter ClC-3 in regulation of the NADPH oxidase. This interest developed after ClC-3 knockout mice were found to have a defect in innate immunity and later demonstrated to have multiple abnormalities in neutrophil function. There are several sub-projects under study including:
Role of anion channels and oxidants in resting neutrophils and primed neutrophils:
Fred S. Lamb, M.D., Ph.D., University of Iowa, Department of Pediatrics
Francis Miller, M.D. University of Iowa, Department of Internal Medicine
Role of NADPH oxidase and anion channels in cell volume regulation and cell motility in neutrophils
Fred S. Lamb, M.D., Ph.D., University of Iowa, Dept. of Pediatrics A. Paige Davis, M.D., University of Iowa, Dept. of Pediatrics William M. Nauseef, M.D., University of Iowa, Department of Medicine David R. Soll, Ph.D., University of Iowa, Dept of Biology
A second ongoing project in the laboratory focuses on understanding the early components of the innate immune response to bacterial pathogens in the lung. We are specifically interested in dissecting neutrophil-endothelial cell interactions, and understanding the determinants of neutrophil transendothelial migration. These studies focus on two very distinct pulmonary pathogens: Streptococcus pneumoniae, the leading cause of community acquired pneumonia, and Francisella tularensis, a potential agent for bioterrorism. We have developed an in vitro model of neutrophil transmigration that includes stimulation of primary human pulmonary endothelial cells with live bacteria, followed by the addition of human PMNs. For our studies of Francisella tularensis, we are also exploring interactions between this pathogen and alveolar epithelial cells.
Moreland JG, Hook JS, Bailey G, Ulland, T, and Nauseef WM.Francisella tularensis directly interacts with the endothelium and recruits neutrophils with a blunted inflammatory phenotype. Am J Physiol Lung Cell Mol Physiol published on April 3, 2009, as doi:10.1152/ajplung.90332.2008
Drake JM, Strohbehn G, Bair TB, Moreland JG, and Henry MD. ZEB1 Enhances Transendothelial Migration and Represses the Epithelial Phenotype of Prostate Cancer Cells. Molecular Biology of the Cell, in Press, published February 18, 2009 as 10.1091/mbc.E08-10-1076
Lamb FS, Moreland JG, Miller FJ. Electrophysiology of reactive oxygen production in signaling endosomes. Antioxidants and Redox Signaling, In Press, January 2009.
Volk APD, Heise CK, Hougen JL, Artman CM, Volk KA, Wessels D, Soll DR, Nauseef WM, Lamb FS,Moreland JG. ClC-3 and ICLswell are required for normal neutrophil chemotaxis and shape change. Journal of Biological Chemistry, JBC Papers in Press published on October 7, 2008 as doi:10.1074/jbc.M803141200
Matsuda JJ, Filali MS, Volk KA, Collins MM, Moreland JG, and Lamb FS. Overexpression of CLC-3 in HEK293T cells yields novel currents that are pH dependent. American Journal of Physiology: Cell Physiology. 2008; 294 (1):C251-62.
Moreland JG, Davis AP, Matsuda JJ, Hook JS, Bailey G, Nauseef WM, Lamb FS. Endotoxin priming of neutrophils requires NADPH-oxidase generated oxidants and is regulated by the anion transporter ClC-3. Journal of Biological Chemistry, 2007; 282 (47): 33958-67.
Morriss J, Moreland JG, Burkhart H, Kao S. Pre-Surgical Evaluation of Interrupted Aortic Arch With 3-Dimensional Reconstruction of CT Images. Ann Thorac Surg, 2007, 84: 299.
Femling JK, Cherny VV, Morgan D, Rada B, Davis AP, Czirják G, Enyedi P, England SK, Moreland JG, Ligeti E, Nauseef WM, DeCoursey TE: The Antibacterial Activity of Human Neutrophils and Eosinophils Requires Proton Channels but Not BK Channels. J Gen Physiol. 2006, 127: 659-672.
Moreland JG, Davis AP, Bailey G, Nauseef WM, Lamb FS: Anion channels, including ClC-3, are required for normal neutrophil oxidative function, phagocytosis, and transendothelial migration. Journal of Biological Chemistry 2006 May 5;281(18):12277-88.
Moreland JG, and Bailey G: Neutrophil transendothelial migration in vitro to Streptococcus pneumoniae is pneumolysin dependent. Am J Physiol Lung Cell Mol Physiol. 2006 May; 290(5):L833-40.
Moreland JG, Bailey G, Nauseef WM, Weiss JP: Organism-specific neutrophil-endothelial cell interactions in response to E. coli, S. pneumoniae, and S. aureus, Journal of Immunology 2004; 172: 426-32.