Biographical Sketch

Research

I study matrix metalloproteinases (MMPs) in lung development, injury and repair. We have been utilizing mice that are deficient in MMP-2, -9 and -14 (MT1-MMP) and the MMP inducer, basigin, to study the role of proteases in lung development and response to injury with acute and chronic cigarette smoke exposure, bleomycin, naphthalene and LPS. In addition our laboratory is involved in the study of blood monocytes and alveolar macrophages of smokers with and without emphysema to better understand why some people who smoke develop emphysema while others do not. We have discovered that MT1-MMP is necessary for alveolar development and the development of pores of Kohn, which holes or communications between alveolar spaces [seen in WT mice (A), but not MT1-MMP KO mice (B)]. Since MT1-MMP is a collagenase and the widening of pores of Kohn may be the first step in the development of emphysema we are trying to understand the contribution of increased MT1-MMP seen in the lung tissue of former smokers with COPD [seen by in situ hybridization (A, B and C) and immunohistochemistry (D, E and F) in airway epithelial cells A and D and alveolar macrophages B and E], but not in the lungs of people without COPD [C, F]. We have discovered that the airway epithelial expression of MT1-MMP is critical for proliferative responses in acute small airway injury repair. Now we are evaluating the role of MT1-MMP expression in blood monocytes and alveolar macrophages in both mouse model and human samples to determine the contribution of this protease in emphysema pathogenesis. We propose that MMP-14 is involved in both the emigration of blood monocytes into the tissue and the destruction of collagen in the alveolar walls.

Publications

1. Adair-Kirk TL, Atkinson JJ, Broekelmann TJ, Doi M, Tryggvason K, Miner JH, Mecham RP, Senior RM. Jul 2003. A site on laminin alpha5, AQARSAASKVKVSMKF, induces inflammatory cell production of matrix metalloproteinase-9 and chemotaxis. J Immunology. 171:398-406.

2. Atkinson JJ, Senior RM. Jan 2003. Matrix metalloproteinase-9 in lung remodeling. Am J Respir Cell Mo. Biol. 28:12-24.

3. Hirsche TO, Atkinson JJ, Bahr S, Belaaouaj A. April 2004. Deficiency in neutrophil elastase does not impair neutrophil recruitment to inflamed sites. Am J Respir Cell Mol Biol. 30(4):576-84.

4. Atkinson JJ, Holmbeck K, Yamada S, Birkedal-Hansen H, Parks WC, Senior RM. 2005 Membrane-type 1 Matrix Metalloproteinase is Required for Normal Alveolar Development. Dev. Dyan. 232:1079-1090.

5. Adair-Kirk TL, Atkinson JJ, Broekelmann TJ, Miner JH, Mecham RP, Senior RM. 2005. A Chemotactic Peptide from Laminin ?5 Functions as a Regulator of Inflammatory Immune Responses via TNF?-mediated Signaling. J Immunology. 174:1621-9.

6. Elizur A, Orscheln RC, Ferkol TW, Atkinson JJ, Dunne WM Jr, Buller RS, Armstrong JR, Mardis ER, Storch GA, Cannon CL. 2007. Panton-Valentine Leukocidin-positive methicillin-resistant Staphylococcus aureus lung infection in patients with cystic fibrosis. Chest. 131:1781-25.

7. Atkinson JJ, Toennies H, Holmbeck K, Senior RM. 2007. Membrane-type 1 Matrix Metalloprotienase is Necessary for Distal Airway Epithelial Repair and Keratinocyte Growth Factor Expression After Acute Injury. Am J Physiol: Lung Cell Mol Physiol. 293(3): p. L600-L610.

Book Chapters/Reviews

1. Atkinson JJ, Shapiro SD. Neutrophil-Mediated Eosinophil Transmigration: Parting the Red Sea or Leaving Bread Crumbs. Am J Respir Cell Mol Biol. 2006;34:645-646. (Editorial)

2. Atkinson JJ, Senior RM. Chronic Obstructive Pulmonary Disease: Epidemiology, Pathophysiology and Pathogenesis. In. Editor Fisman A. P., Fishman’s Pulmonary Diseases and Disorders, Edition 4, Chapter 41. McGraw-Hill, New York. (in press)

3. Atkinson JJ, Brody SL. 2007. Epithelial Repair and Regeneration. In. Editor Zander, D. S., Molecular Pathology of Lung Disease. Chapter 45. Springer. New York. (in press)

4. Atkinson JJ, Senior RM. 2006. Trying to Understand Chronic Obstructive Pulmonary Disease: Investigating Pandora’s box in search of hope. Touch Briefings: US Respiratory Disease.

5. Atkinson JJ, Rosenbluth D. Congenital Lung Diseases. In. Editor Dale, D., ACP Medicine. Chapter 16. (in press).