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Dr. John Repine's Laboratory

Investigating Inflammation, Oxidative Stress and Antioxidant Deficiency


Repine lab
J. Evans, J. Repine, MD, N. Elkins, P. Wilson

Our research is focused on finding better ways to diagnose, treat and prevent inflammation, antioxidant deficiency and oxidative stress related diseases and aging.  These investigations target a number of important interrelated disease areas including the following:

  1. The Acute Respiratory Distress Syndrome (ARDS or Acute Lung Injury).  ARDS is a highly-fatal disease (approximately 40% death rate) that occurs following infection, trauma, pancreatitis, multiple transfusions and multiple other common predisposing insults.  ARDS kills more Americans (estimated at 80,000) each year than breast cancer and AIDS combined.  ARDS takes the lives of many soldiers.  We are presently pursuing a number of approaches (some patent protected) for predicting ARDS development in susceptible individuals and developing therapies for treating and preventing this deadly condition.
  2. The Metabolic Syndrome. This is a common condition that occurs in aging individuals who develop abdominal obesity, hypertension, abnormal blood lipid levels, premature cardiovascular disease and/or increased blood glucose levels that resemble changes seen in diabetes.  We are testing an animal model that lives longer and appears to resist metabolic syndrome development.  This work will create new insights regarding the causes and treatment of this disease and related disorders that may eventually impact as many as 20% of the world’s population.
  3.  Age-Related Macular Degeneration (AMD).  AMD is the leading cause of blindness in the elderly.  It is a very common disorder that may afflict as many as 8% of individuals who are 70 years of age or older. AMD starts as a dry form that then unpredictably changes to a more severe wet form. There is no known effective treatment for dry ARDS.  We are developing a new approach that has the potential of reducing dry AMD and hopefully preventing it from evolving into wet AMD.
  4. Aging.  We are testing a unique animal model that lives longer, can exercise more and can breathe pure oxygen indefinitely without succumbing.  The model holds potential for understanding and reducing the effects of aging and age-related disorders.

Dr. Richard Bowen, DMV, Colorado State University, Fort Collins, Colorado

Robert Scheinman, PhD, SOP, CU Anschutz

Oscar Reiss, PhD, Retired, CU Anschutz

John J. Hall, PhD, NIST-University of Colorado, Boulder

Jun Ye, PhD, NIST-University of Colorado, Boulder

Thomas Meersman, PhD, University of Notthingham, England

  1. Repine, J.E., White, J.G., Clawson, C.C. and Holmes, B.M.:  Effects of phorbol myristate acetate on the metabolism and ultrastructure of neutrophils in chronic granulomatous disease. J. Clin. Invest. 54:83-90, 1974 (PMID: 4366245).
  2. Repine, J.E., Eaton, J.W., Anders, M.W., Hoidal, J.R. and Fox, R.B.:  Generation of hydroxyl radical by enzymes, chemicals, and human phagocytes in vitro:  Detection using the anti-inflammatory agent - Dimethyl sulfoxide.  J. Clin. Invest. 64:1642-1651, 1979 (PMID: 500830).
  3. Repine, J.E., Pfenninger, O.W., Talmage, D.W., Berger, E.M. and Pettijohn, D.E.:  Dimethyl sulfoxide prevents DNA nicking mediated by ionizing radiation or iron/hydrogen peroxide-generated hydroxyl radical.  Proc. Natl. Acad. Sci. (USA) 78:1001-1003, 1981 (PMID: 6940118).
  4. Repine, J.E., Fox, R.B. and Berger, E.M.:  Hydrogen peroxide kills Staphylococcus aureus by reacting with staphylococcal iron to form hydroxyl radical.  J. Biol. Chem. 256:7094 7096, 1981 (PMID: 6265438).
  5. Tate, R.M., Morris, H.G., Schroeder, W.R. and Repine, J.E.: Oxygen metabolites stimulate thromboxane production and vasoconstriction in isolated saline-perfused rabbit lungs. J. Clin. Invest. 74:608-613, 1984 (PMID: 6547730).
  6. Toth, K.M., Clifford, D.P., Berger, E.M., White, C.W. and Repine, J.E.:  Intact human erythrocytes prevent hydrogen peroxide mediated damage to isolated perfused rat lungs and cultured bovine pulmonary artery endothelial cells. J. Clin. Invest. 74:292-295, 1984 (PMID: 6330176).
  7. White, C.W., Ghezzi, P., Dinarello, C.A., Caldwell, S.A., McMurtry, I.J. and Repine, J.E.:  Recombinant tumor necrosis factor/cachectin and interleukin 1 pretreatment decreases lung oxidized glutathione accumulation, lung injury and mortality in rats exposed to hyperoxia.  J. Clin. Invest. 79:1868 1873, 1987 (PMID: 3495553).
  8. Curtis, W.E., Muldrow, M.E., Parker, N.B., Barkley, R., Linas, S.L. and Repine, J.E.:  N,N' Dimethyl-thiourea dioxide formation from N,N' dimethylthiourea reflects hydrogen peroxide concentrations in simple biological systems.  Proc. Natl. Acad. Sci. (USA) 85:3422  3425, 1988 (PMID: 3130627).
  9. Brown, J.M., Terada, L.S., Grosso, M.A., Whitmann, G.J., Velasco, S.E., Patt, A., Harken, A.H. and Repine, J.E.:  Xanthine oxidase produces hydrogen peroxide which contributes to reperfusion injury of ischemic isolated perfused rat hearts.  J. Clin. Invest. 81: 1297 1301, 1988 (PMID: 3127425).
  10. Patt, A., Harken, A.H., Burton, L.K., Rodell, T.C., Piermattei, D., Schorr, W.J., Parker, N.B., Berger, E.M., Horesh, I.R., Linas, S.L., Cheronis, J.C. and Repine, J.E.:  Xanthine oxidase derived hydrogen peroxide contributes to ischemia reperfusion induced edema in gerbil brains.  J. Clin. Invest. 81:1556 1562, 1988 (PMID: 3130395).
  11. Adler, K.B., Holden-Stauffer, W.J. and Repine, J.E.:  Oxygen metabolites stimulate release of high molecular weight glycoconjugates by cell and organ cultures of rodent respiratory epithelium via an arachidonic acid-dependent mechanism.  J. Clin. Invest. 85:75-85, 1990 (PMID: 2153154).
  12. Guidot, D.M., McCord, J.M., Wright, R.M. and Repine, J.E.:  Absence of electron transport (Rho O state) restores growth of a manganese superoxide dismutase deficient Saccharomyces cerevisiae in hyperoxia: evidence for electron transport as a major source of superoxide generation in vivo.  J. Biol. Chem. 268: 26699 26703, 1993 (PMID: 8253804).
  13. Guidot, D.M., Repine, M.J., Westcott, J.Y. and Repine, J.E.:  Intrinsic 5 lipoxygenase activity is required for neutrophil responsivity.  Proc. Natl. Acad. Sci. (USA) 91:8156-8159, 1994 (PMID: 8058773).
  14. Abraham, E., Bursten, S., Shenkar, R., Allbee, J., Tudor, R., Woodson, P., Guidot, D.M., Rice, G.,Singer, J.W. and Repine, J.E.:  Phosphatidic acid signaling mediates lung cytokine expression and lung inflammatory injury  following hemorrhage.  J. Exp. Med. 181:569-575, 1995 (PMID: 7836912).
  15. Cleveland, Z.I., Pavlovskaya, G.E., Elkins, N.D., Stupic, K.F., Repine, J.E. and Meersman, T.:  Hyperpolarized 83Kr MRI of lungs.  J. Mag. Reson. 195:232-237, 2008 (PMID: 18948043).
  16. Repine, J.E., Reiss, O.K., Elkins, N., Chughtai, A.R. and Smith, D.M. Effects of fine carbonaceous particles containing high and low unpaired electron spin densities on lungs of female mice. Trans. Res. 152:185-193, 2008 (PMID: 18940721).