Alejandro Comellas, M.D. (Associate Member)
Assistant Professor, Department of Internal Medicine, The University of Iowa

http://www.int-med.uiowa.edu/Divisions/Pulmonary/Directory/AlejandroComellas.html

Research Interest    

Dr. Comellas' research interest is in the area of acute lung injury, with a focus on two specific aspects that maintain the integrity of the alveolar epithelial barrier: (1) the regulation of tight junctions in the alveolar epithelium and (2) mechanisms that involve reabsorption of alveolar fluid edema. Dr Comellas laboratory is interested in developing strategies that will preserve the integrity of the epithelial barrier by stabilizing the alveolar epithelial tight junctions and by up-regulating the mechanisms involved in the alveolar fluid clearance. Currently the laboratory has identified that reactive oxygen species activate PKC zeta which in turn promotes the endocytosis of Na,K-ATPase and also decreases the abundance of different tight junction proteins. The laboratory is currently planing to use virus-directed gene therapies to the lung that include upregulation of different tight junction proteins, antioxidant enzymes such as MnSOD, CuZnSOD and Catalase, and the Na,K-ATPase with the goal of preserving an intact and functional alveolar epithelial barrier. In addition, the laboratory is planning to deliver siRNA against some of the signaling molecules that are involved in the downregulation of tight junction proteins and the Na,K-ATPase. This project is expected to lead to a better understanding of the pathophysiology of acute lung injury and the development of future strategies for the treatment of patient with acute respiratory distress syndrome (ARDS).

Selected Publications:

Pesce L, Guerrero C, Comellas A, Ridge KM, Sznajder JI. beta-agonists regulate Na,K-ATPase via novel MAPK/ERK and rapamycin-sensitive pathways. FEBS Lett 2000 Dec 15;486(3):310-4.

Azzam ZS, Saldias FJ, Comellas A, Ridge KM, Rutschman DH, Sznajder JI. Catecholamines increase lung edema clearance in rats with increased left atrial pressure. J Appl Physiol 2001 Mar;90(3):1088-94.

Saldias FJ, Comellas A, Pesce , Lecuona E, Sznajder JI. Dopamine increases lung liquid clearance during mechanical ventilation. Am J Physiol Lung Cell Mol Physiol. 2002 Jul;283(1):L136-43.

Comellas AP, Pesce LM, Azzam Z, Saldias FJ, Sznajder JI. Scorpion venom decreases lung liquid clearance in rats. Am J Respir Crit Care Med. 2003 Apr 15;167(8):1064-7.

Pesce L, Comellas A, Sznajder JI. {beta} -adrenergic agonists regulate the Na,K-ATPase via the p70s6K. Am J Physiol Lung Cell Mol Physiol. 2003 Oct; 285(4): L802-7. Epub 2003 Apr 18.

Upadhyay D, Lecuona E, Comellas A, Kamp DW, Sznajder JI. Fibroblast growth factor-10 upregulates Na,K-ATPase via the MAPK pathway. FEBS Lett. 2003 Jun 19;545(2-3):173-6.

Sam S, Corbridge TC, Mokhlesi B, Comellas AP, Molitch ME. Cortisol levels and mortality in severe sepsis. Clinical Endocrinology. 2004 Jan; 60:29-35.

Azzam ZS, Adir Y, Crespo A, Comellas A, Lecuona E, Dada LA, Krivoy N, Rutschman DH, Sznajder JI, Ridge KM. Norepinephrine Increases Alveolar Fluid Reabsorption and Na,K-ATPase Activity. Am J Respir Crit Care Med. 2004 Jul 15.

Comellas AP, Dada LA, Lecuona E, Pesce LM, Chandel NS, Quesada N, Budinger GR, Strous GJ, Ciechanover A, Sznajder JI. Hypoxia-Mediated Degradation of Na,K-ATPase via Mitochondrial Reactive Oxygen Species and the Ubiquitin-Conjugating System. Circ Res. 2006 May 26;98(10):1314-22. Epub 2006 Apr 13.

Yakov P, Comellas A, Levantini E, Ingenito E, Shapiro S. EGF and claudin-2 participate in A549 permeability and remodeling: Implications for non-small cell lung cancer tumor colonization. Molecular Carcinogenesis. 2008 Oct 21 [Epub ahead of print]

Comellas AP, Briva A, Dada LA, Butti ML, Trejo H, Yshii C, Azzam Z, Litvan J, Chen J, Lecuona E, Pesce LM, Yanagisawa M, Sznajder JI. Endothelin-1 Impairs Alveolar Epithelial Function via Endothelial ET-B Receptor. Am J Respir Crit Care Med. 2008 Oct 23 [Epub ahead of print]

Publications from PubMed