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Dr. Ingbar's clinical interests include acute respiratory distress syndrome, pulmonary edema, massive hemoptysis, management of respiratory failure, and pulmonary embolism.
Dr. Ingbar is researching alveolar epithelial repair and clearance of alveolar edema fluid. The principal objective of this research is to understand the regulation of alveolar epithelial ion transport and the specific proteins involved (sodium pump, chloride channels and sodium channel) during lung development, and lung injury and repair. The long-term goal is to develop in vitro and in vivo strategies to augment alveolar fluid clearance. Current projects includes studies of hormonal effects on alveolar fluid clearance and the transport proteins, particularly the sodium pump – Na,K-ATPase. We are examining the mechanisms by which hormones augment sodium pump activity, including effects on intracellular trafficking, translation and transcription. Studies examine the responses during injury/repair and compare these with developmental regulation. The lab uses a combination of molecular biologic, biochemical and physiologic approaches, including studies in vitro and in vivo. Given the widespread involvement of oxidants in lung disease, we also study the effects of oxidants on these proteins, and their regulation. Injury model studies include hyperoxia, post-bone marrow transplant and bio-defense agents. Finally the lab is interested in developing new methods to promote alveolar epithelial repair, such as stimulating alveolar epithelial migration. The barrier functions of the epithelium are critical in lung development, repair and prevention of ongoing alveolar flooding.
Lei J, Mariash CN, Bhargava M, Wattenberg EV, Ingbar DH. T3 increases Na,K-ATPase activity via a MAPK ERK1/2 dependent pathway in rat adult alveolar epithelial cells. Am J Physol Cell Mol Physiol, 2008; 294(4):749-54.
Bhargava M, Runyon M, Smirnov D, Lei J, Groppoli TJ, Mariash C, Podobinski J, Wangensteen OD, Ingbar DH. T3 rapidly stimulates alveolar fluid clearance in nomal and hyperopxia-injured rat lungs. Am J Resp Crit Care Med, 2008; 178:506-512.
Lei J, Bhargava M, Ingbar DH. Cell-specific signal transduction pathways regulating Na+-K+-ATPase. Focus on "short-term effects of thyroid hormones on the Na+-K+-ATPase activity of chick embryo hepatocytes during development: focus on signal transduction". Am J Physiol Cell Physiol, 2009; 296(1):C1-3.
Bhargava M, Lei J, Ingbar DH. Non-genomic actions of L thyroxine and 3,5,3' Triiodo-L-Thyronine: Focus on C-90604-2007 Short-term effects of thyroid hormones. Am J Physiol Cell Physiol, 2009; 296(5):C977-9. PMC: 2681374
Ingbar DH, Bhargava M, O'Grady SM. Mechanisms of alveolar epithelial chloride absorption. Am J Physiol Lung Cell Mol Physiol. 2009;297(5):L813-5.
Cobb JP, Ognibene FP, Ingbar DH, Mann HJ, Hoyt DB, Angus DC, Thomas AV Jr, Danner RL, Suffredini AF. Forging a critical alliance: Addressing the research needs of the United States critical illness and injury community. Crit Care Med. 2009;37(12):3158-60.
Wise RA, Bartlett SJ, Brown ED, Castro M, Cohen R, Holbrook JT, Irvin CG, Rand CS, Sockrider MM, Sugar EA; American Lung Association Asthma Clinical Research Centers. Randomized trial of the effect of drug presentation on asthma outcomes. J Allergy Clin Immunol. 2009 Sep;124 (3):436-44, 444e1-8.Epub 2009 Jul 25.
Panoskaltsis-Mortari A, Cooke KR, Madtes DK, Belperio JA, Ingbar DH et al. Idiopathic pneumonia syndrome: research update. Am J. Respir Crit Care Med (2009, in revision).
Bhargava M, Runyon M, Smirnov D, Lei J, Groppoli T, Mariash C, Podobinski J, Wangensteen OD, Ingbar DH. Triiodo-l-thyronine rapidly stimulates alveolar fluid clearance in normal and hyperoxia-injured rat lungs. Am J Resp Crit Care Med, 2008;178(5):506-12. PMCID: PMC2542429