Karen A. Fagan, M.D.

Karen A. Fagan, M.D.Professor, Internal Medicine and Pharmacology
Director, Pulmonary and Critical Care Medicine Division

M.D.: University of California at San Diego
Post-doctoral: University of Texas Southwestern Medical School and University of Colorado Health Sciences Center

Phone: (251) 471-7914

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

  1. 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
  2. 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
  3. 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
  4. Oka M, Fagan KA, Jones PL, McMurtry IF. Therapeutic potential of RhoA/Rho kinase inhibitors in pulmonary hypertension. Br J Pharmacol. Jun 9. 2008
  5. Oka M, Karoor V, Nagaoka T, Sakao E, Limbird J, Imamura M, Gebb SA, Fagan KA, and IF McMurtry. Dehydroepiandrosterone upregulates soluble guanylate cyclase and inhibits hypoxic pulmonary hypertension in rats. Cardiovasc Res. Jun 1;74(3):377-87. 2007
  6. 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
  7. 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
  8. Stenmark K, Fagan KA, and M Frid. Hypoxic Pulmonary Vascular Remodeling: Cellular and Molecular Mechanisms. (Invited Review) Circ Res. 99:675-91. 2006
  9. 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
  10. 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
  11. Bull TM, Fagan KA, Badesch DB. Pulmonary vascular manifestations of mixed connective tissue disease. Rheum Dis Clin North Am. (3):451-64. 2005
  12. 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
  13. 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
  14. Fagan KA. Potential Genetic Contributions to Nonidiopathic, Nonfamilial Pulmonary Hypertension. (Invited Review) Advances in Pulmonary Hypertension, 4(1):24-28, 2005
  15. Fagan KA, Bull TM,. Badesch DB, and NF Voelkel. Metastatic Cancer While on Continuous Prostacyclin Therapy. Chest, 128: 619-620S, 2005
  16. 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
  17. 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
  18. Bull TM, Fagan KA, and DB Badesch. Pulmonary hypertension: The latest treatments. J Resp Dis. 25:242-253, 2004
  19. 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
  20. 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
  21. 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
  22. 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
  23. 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
  24. Fagan KA, Collier DH, and DB Badesch. Scleroderma and Pulmonary Hypertension. Rev Bras Reumatol, 43(5):294-301, 2003
  25. 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
  26. 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
  27. Fagan KA, DH Collier, and DB Badesch, Scleroderma Associated Pulmonary Hypertension. (Invited Review). Advances in Pulmonary Hypertension, 1(2): 5-9, 2002
  28. Fagan KA and DB Badesch. Pulmonary Hypertension Associated with Connective Tissue Disease (Invited Review). Progress in Cardiovascular Diseases, 45:225-34, 2002
  29. 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
  30. 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
  31. 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
  32. 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
  33. 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
  34. 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
  35. Fagan KA, McMurtry IF, and DM Rodman. Role of Endothelin-1 in Lung Disease. (Invited Review) Respiratory Research. 2:90-101, 2001
  36. 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
  37. 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
  38. 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
  39. Wynne K, Fagan KA, and DB Badesch. Primary Pulmonary Hypertension. Women's Health in Primary Care. 2:489-503, 1999
  40. 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
  41. 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
  42. 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
  43. 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
  44. Fagan KA, Hepler LK, McMurtry IF, and DM Rodman. NO inhibits transgene expression in vascular smooth muscle cells. Chest (Supp) 114:85S, 1998