Karen A. Fagan, M.D.

M.D.   University of California at San Diego
Post-doctoral   University of Texas Southwestern Medical School and
University of Colorado Health Sciences Center
Current Position   Professor, Internal Medicine and Pharmacology
Chief, Pulmonary and Critical Care Medicine Division
Phone   (251) 471-7914
E-mail   kfagan@health.southalabama.edu

Research Interests

Dr. Fagan's research in pulmonary arterial hypertension revolves around several key projects all using animal models of PAH to better understand the pathophysiology of this fatal disease and identify potential new therapeutic targets. Dr. Fagan is also a clinician specializing in the treatment of patients with PAH at the University of South Alabama Pulmonary Hypertension Center. Current research projects including the role of inflammation in the pathogenesis of PAH, specifically the role of IL-6. Using transgenic animals that overexpress IL-6, we plan to investigate downstream signals and their role in promoting the development of PAH. In another project, the role of integrins (proteins that link the extracellular matrix to cells) and their role in controlling cellular functions in PAH (such as contraction) are also being investigated.

Representative Publications

West J, Harral J, Lane K, Deng Y, Ickes B, Crona D, Albu S, Stewart D, and Fagan K. Mice Expressing BMPR2 Transgene in Smooth Muscle Develop Pulmonary Vascular Lesions. Accepted, Am J Physiol Lung Cell Mol Physiol, 8/ 2008

Homma N, Nagaoka T, Karoor V, Imamura M, Taraseviciene-Stewart L, Walker LA, Fagan KA, McMurtry IF, Oka M. Involvement of RhoA/Rho kinase signaling in protection against monocrotaline-induced pulmonary hypertension in pneumonectomized rats by dehydroepiandrosterone. Am J Physiol Lung Cell Mol Physiol. Jul;295(1):L71-8. 2008

Frei AC, Guo Y, Jones DW, Pritchard KA Jr, Fagan KA, Hogg N, Wandersee NJ. Vascular dysfunction in a murine model of severe hemolysis. Blood. Jul 15;112(2):398-405. 2008

Oka M, Fagan KA, Jones PL, McMurtry IF. Therapeutic potential of RhoA/Rho kinase inhibitors in pulmonary hypertension. Br J Pharmacol. Jun 9. 2008

Oka M, Karoor V, Nagaoka T, Sakao E, Limbird J, Imamura M, Gebb SA, Fagan KA, and IF McMurtry. Dehydroepiandersteone upregulates soluble guanylate cyclase and inhibits hypoxic pulmonary hypertension in rats. Cardiovasc Res. Jun 1;74(3):377-87. 2007

Irwin D, Helm K, Campbell N, Imamura M, Fagan KA, Harral J, Carr M, Young KA, Klemm D, Gebb S, Dempsey EC, West J, Majka S. Neonatal lung side population cells demonstrate endothelial potential and are altered in response to hyperoxia-induced lung simplification. Am J Physiol Lung Cell Mol Physiol. Oct;293(4):L941-51. 2007

Hagen M , Steudel W, Carr M, Lane K, Fagan K, Rodman D, J West. Interaction of Interleukin-6 and the BMP Pathway in Pulmonary Smooth Muscle and Endothelium. Am J Physiol Lung Cell Mol Physiol. 2007 Jun;292(6):L1473-9. 2007

Stenmark K, Fagan KA, and M Frid. Hypoxic Pulmonary Vascular Remodeling: Cellular and Molecular Mechnanisms. (Invited Review) Circ Res. 99:675-91. 2006

Dovico S, Ickes B, Schmidt P,Golembeski SM, West J, and KA Fagan. IL-6 causes pulmonary hypertension, vascular remodeling, and pulmonary artery smooth muscle cell proliferation through activation of Jak/Stat signalling. In review, 2007

Golembeski S, Schmidt P, Dovico S, Gebb SA, and KA Fagan. Oxidative stress and decreased NO activity in intermittent hypoxia-induced pulmonary hypertension. In review, 2007

Bull TM, Fagan KA, Badesch DB. Pulmonary vascular manifestations of mixed connective tissue disease. Rheum Dis Clin North Am. (3):451-64. 2005

Littler CM, Wehling CA, Wick MJ, Fagan KA, Cool CD, Messing RO, Dempsey EC. Divergent Contractile And Structural Responses Of The Murine PKC-Epsilon Null Pulmonary Circulation To Chronic Hypoxia. Am J Phys. 289: L1083-1093, 2005

Golembeski, SM West, Tada Y, and KA Fagan. IL-6 causes Mild Pulmonary Hypertension and Augments Hypoxia-Induced Pulmonary Hypertension in Mice, Chest, 128:572-573S, 2005

Fagan KA. Potential Genetic Contributions to Nonidiopathic, Nonfamilial Pulmonary Hypertension. (Invited Review) Advances in Pulmonary Hypertension, 4(1):24-28, 2005

Fagan KA, Bull TM,. Badesch DB, and NF Voelkel. Metastatic Cancer While on Continuous Prostacyclin Therapy. Chest, 128: 619-620S, 2005

Rodman DM, Reese K, Harral J, Fouty B, Wu S, West J, Hoedt-Miller M, Tada Y, Li KX, Cool C, Fagan K, Cribbs L. Low-voltage-activated (T-type) calcium channels control proliferation of human pulmonary artery myocytes. Circ Res. Apr 29;96(8):864-72. 2005

Nagaoka T, Fagan KA, Gebb SA, Morris KG, Suzuki T, Shimokawa H, McMurtry IF, and M Oka. Inhaled Rho kinase inhibitors are potent and selective vasodilators in rat pulmonary hypertension. Am J Resp Crit Care Med. 171:494-499. 2005

Bull TM, Fagan KA, and DB Badesch. Pulmonary hypertension: The latest treatments. J Resp Dis. 25:242-253, 2004

Hartsfield CL, McMurtry IF, Ivy DD, Morris KG, Vidmar S, Rodman DM and KA Fagan. Cardioprotective and vasomotor effects of HO activity during acute and chronic hypoxia. Am J Phys, 287LH2009-2015, 2004

West J, Buchholz M, Fierro A, Y Tada, Fagan K, and DM Rodman. Adenoviral gene transfer to the neonatal rat pulmonary circulation. J Gene Med, 6:734-9 2004

West J, Fagan KA, Steudel W, Fouty B, Harral J, Hoedt-Miller M, Tada Y, Ozimek J, Tuder R, and DM Rodman. Transgenic Mice expressing a human BMPRII mutation in vascular smooth muscle develop pulmonary arterial hypertension. Circ Res, 94:1109-1114. 2004

Fagan KA, Oka M, Bauer NR, Gebb SA, Ivy DD, Morris KG , and IF McMurtry. Attenuation of acute hypoxic pulmonary vasoconstriction and hypoxic pulmonary hypertension in mice by inhibition of Rho-kinase. Am J Phys, 287:L656-664, 2004

McMurtry IF, Bauer NR, Fagan KA, Nagaoka T, Gebb SA, and M Oka. Hypoxia and Rho/Rho-Kinase Signaling: Lung development versus hypoxic pulmonary hypertension. Adv Exp Med Biol, 543:127-37, 2003

Fagan KA, Collier DH, and DB Badesch. Scleroderma and Pulmonary Hypertension. Rev Bras Reumatol, 43(5):294-301, 2003

Le Cras TD, Hardie WD, Pyles DB, Fagan KA, Whitsett JA, and TR Korfhagen. Transforming growth factor-alpha causes pulmonary vascular disease through autocrineparacrine signaling in distal epithelial cells. Am J Phys, 285: L1043-1054, 2003

Littler CM, Morris KG, Fagan KA, McMurtry IF, Messing RO and EC Dempsey. Protein Kinase C Epsilon Null Mice Have Decreased Hypoxic Pulmonary Vasoconstriction. Am J Phys, 284(4):H1321-31, 2003

Fagan KA, DH Collier, and DB Badesch, Scleroderma Associated Pulmonary Hypertension. (Invited Review). Advances in Pulmonary Hypertension, 1(2): 5-9, 2002

Fagan KA and DB Badesch. Pulmonary Hypertension Associated with Connective Tissue Disease (Invited Review). Progress in Cardiovascular Diseases, 45:225-34, 2002

Fujita M, Mason RJ, Cool C, Shannon JM, Hara N, and Fagan KA. Pulmonary hypertension in TNF-a-overexpressing mice is associated with decreased VEGF gene expression. J App Phys, 93:2162-2170, 2002

Fouty BW, Grimison B, Fagan KA, Le Cras, TD, Wright Harral J, Hoedt-Miller M, Sclafani RA, and DM Rodman. Central role for p27-kip1 in modulating pulmonary artery smooth muscle cell proliferation. Submitted, Am J Resp Cell Molec Biol, 25: 652-658, 2001

Fagan KA and JV Weil. Potential genetic contributions to control of the pulmonary circulation and ventilation at high altitude. (Invited Review) High Altitude Medicine. 2: 165-171, 2001

Fagan KA, Morissey B, Fouty BW, Sato K, Wright Harral J, Morris KG, Miller M, Vidmar S, McMurtry IF, and DM Rodman. Upregulation of nitric oxide synthase following chronic hypobaric hypoxia in mice with severe pulmonary hypertension. Respiratory Research. 2: 306-313, 2001

Fagan KA. Highlighted Topics: Physiological and Genomic Consequences of Intermittent Hypoxia: Selected Contribution: Pulmonary hypertension in mice following intermittent hypoxia. J App Phys. 90:2502-2507, 2001

Fujita M, Shannon JM, Irvin CG, Augustin A, Fagan KA, and RJ Mason. Overexpression of TNF-alpha in the lungs produces pulmonary hypertension and a physiologic phenotype consistent with emphysema. Am J Phys. 280:L39-L49, 2001

Fagan KA, McMurtry IF, and DM Rodman. Role of Endothelin-1 in Lung Disease. (Invited Review) Respiratory Research. 2:90-101, 2001

Maloney JP, Halbower AC, Fouty BF, Fagan KA, Balasubramaniam V, Pike A, Fennessy P, and M Moss. Systemic absorption of enteral feeding dye during critical illness. New Eng J Med. 343(14)1047-8, 2000

Fagan KA. McMurtry IF, and DM Rodman. Nitric Oxide Synthase in Pulmonary Hypertension: Lessons from Knockout Mice. (Invited Review) Physiological Research. 49:539-45, 2000

Hocher B, Schwarz A, Fagan KA, Thone-Reineke C, Ei-Hag K, Elitok S, Bauer C, Neumayer HH, Rodman DM, and F Theuring. Pulmonary fibrosis and lung inflammation in ET-1 transgenic mice. Am J Resp Cell Molec Biol 23:19-26, 2000

Wynne K, Fagan KA, and DB Badesch. Primary Pulmonary Hypertension. Women's Health in Primary Care. 2:489-503, 1999

Tyler RC, Fagan KA, Unfer RC, Gorman C, McClarrion M, Bullock C, and DM Rodman. Vascular inflammation inhibits gene transfer to the pulmonary circulation in vivo. Am J Phys. 277:L1199-1204, 1999

Geraci MW, Gao B, Shepard DC, Moore MD, Westcott JY, Alger LA, Fagan KA, Tuder RM, and NF Voelkel. Selective pulmonary prostacyclin synthase overexpression in transgenic mice protects against the development of hypoxic pulmonary hypertension. J Clin Invest. 103(11):1509-1515, 1999

Fagan KA, Tyler RC, Sato K, Fouty BW, Morris KG, Huang PL, McMurtry IF, and DM Rodman. Relative contributions of endothelial, inducible and neuronal nitric oxide synthase to tone in the murine pulmonary circulation. Am J Phys. 277:L472-478, 1999

Fagan KA, Fouty BW, Tyler RC, Morris KG, Hepler LK, Sato K, LeCras TD, Abman SH, Weinberger HD, Huang PL, McMurtry IF, and DM Rodman. The pulmonary circulation of homozygous or heterozygous eNOS-null mice is hyper-responsive to mild hypoxia. J Clin Invest. 103(2):291-299, 1999

Fagan KA, Hepler LK, McMurtry IF, and DM Rodman. NO inhibits transgene expression in vascular smooth muscle cells. Chest (Supp) 114:85S, 1998

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