Charles Loftin - Ph.D.

Dr. Loftin received a Ph.D. in Toxicology in 1995 from the University of North Carolina at Chapel Hill and a B.S. in Pharmacy in 1989 from Auburn University. Before joining the University of Kentucky, Dr. Loftin was a Research Fellow with the National Institute of Environmental Health Sciences in Research Triangle Park, North Carolina.

Research Interests
Dr. Loftin's research examines the cardiovascular and reproductive effects of medications which inhibit the cyclooxygenases (COX-1 and COX-2). COX-1 and COX-2 catalyze the first committed step in the synthesis of prostanoids, lipid mediators which contribute to numerous physiological and pathophysiological processes.

The two COX isoforms are best known as targets of nonsteroidal anti-inflammatory drugs, such as aspirin and ibuprofen, and the COX-2-selective inhibitors celecoxib and rofecoxib have gained broad acceptance as improved anti-inflammatory medications. Recently, COX-2 inhibitors have been suggested as novel therapy for delaying preterm labor in women. However, Dr. Loftin's studies in mice reveal that the inhibition of COX-2 during pregnancy impedes normal function of the fetal and neonatal cardiovascular system. The inhibition of COX-1 does not produce these adverse effects and is an effective treatment for preterm labor.

To further characterize the mechanisms responsible for these pharmacological effects, Dr. Loftin's research also utilizes mice deficient in the genes encoding the two COX isoforms. His research provides insight for identifying novel therapeutic and/or toxic actions resulting from isoform-selective COX inhibition.

Selected Publications/Presentations

• Tiano HF, Loftin CD, Lee CA, Dunson DB, Rogan EG, Smart RC, Morham SG, Langenbach R. Deficiency of Either Cyclooxygenase-1 or Cyclooxygenase-2 Alters Epidermal Differentiation and Reduces Mouse Skin Tumorigenesis. Cancer Research; 62: 3395-3401, 2002.
• Loftin CD, Trivedi DB and Langenbach R. Cyclooxygenase-1-Selective Inhibition Delays Labor in Mice and Lacks the Adverse Fetal and Neonatal Effects of Cyclooxygenase-2-Selective inhibition. Journal of Clinical Investigation; 110(4):549-57, 2002
• Kim K, Baek SJ, Flake GP, Loftin CD, Calvo BF and Eling TE. Expression and regulation of NAG-1, a anti-tumorigenic protein, in human and mouse colorectal tissue. Gastroenterology; 122(5):1388-98, 2002.
• Xu H, Izon DJ, Loftin CD, and Spain LM. The COX-2 Inhibitor NS-398 Causes T Cell Developmental Disruptions Independent of COX-2 Enzyme Inhibition. Cellular Immunology; 214(2):184-93, 2001.
• Loftin CD, Trivedi DB, Tiano HF, Clark JA, Lee CA, Epstein JA, Morham SG, Breyer MD, Nguyen M, Hawkins BM, Goulet JL, Smithies O, Koller BH and Langenbach R. Failure of Ductus Arteriosus Closure and Remodeling in Neonatal Mice Deficient in Cyclooxygenase-1 and Cyclooxygenase-2. Proceedings of the National Academy of Sciences; 98(3):1059-1064, 2001.
• Langenbach R, Loftin CD, Lee C and Tiano H. Cyclooxygenase knockout mice - Models for elucidating isoform-specific functions. Biochemical Pharmacology; 58:1237-1246, 1999.
• Langenbach R, Loftin CD, Lee C, Tiano H. Cyclooxygenase-deficient mice. A summary of their characteristics and susceptibilities to inflammation and carcinogenesis. Annals of the New York Academy of Sciences; 889:52-61, 1999.
• Langenbach R, Morham SG, Tiano HF, Loftin CD, Ghanayem BI, Chulada PC, Mahler JF, Davis BJ, Lee CA. Disruption of the mouse cyclooxygenase 1 gene. Characteristics of the mutant and areas of future study. Advances in Experimental Medicine and Biology; 407:87-92, 1997.
• Chulada PC, Loftin CD, Winn VD, Young D, Tiano HF, Eling TE and Langenbach R. Relative activities of retrovirally expressed murine prostaglandin synthase-1 and -2 depend on the source of arachidonic acid. Archives of Biochemistry and Biophysics; 330(2):301-13, 1996.
• Loftin CD and Eling TE. Prostaglandin synthase 2 expression in epidermal growth factor-dependent proliferation of mouse keratinocytes. Archives of Biochemistry and Biophysics; 330(2):419-29, 1996.
• Morham SG, Langenbach R, Loftin CD, Tiano HF, Vouloumanos N, Jennette JC, Mahler JF, Kluckman KD, Ledford A, Lee CA and Smithies O. Prostaglandin synthase 2 gene disruption causes severe renal pathology in the mouse. Cell; 83(3):473-82, 1995.
• Langenbach R, Morham SG, Tiano HF, Loftin CD, Ghanayem BI, Chulada PC, Mahler JF, Lee CA, Goulding EH, Kluckman KD, Kim HS and Smithies O. Prostaglandin synthase 1 gene disruption in mice reduces arachidonic acid-induced inflammation and indomethacin-induced gastric ulceration. Cell; 83(3):483-92, 1995.