Education:
Name of school attended: University of Nebraska - Lincoln
Undergraduate degree: B.S. Biochemistry

Current Research Description:

Asbestosis is an inflammatory and fatal fibrotic lung disease affecting the alveolar interstitium, after the inhalation of asbestos fibers. Inflammation and oxidant/antioxidant imbalances are believed to contribute to the pathogenesis of this disease. Extracellular Superoxide Dismutase (ECSOD) is an antioxidant enzyme that has been shown to protect the lung from ROS-mediated damage, inflammation, and interstitial fibrosis. However, the mechanisms ECSOD inhibits pulmonary fibrosis and inflammation remain unclear. The proposed project focuses on elucidating the protective mechanisms of ECSOD in asbestosis.

Our laboratory has shown that extracellular matrix (ECM) components like collagen and hyaluronic acid are highly sensitive to oxidative fragmentation and once fragmented are potent chemoattractants and activators of inflammatory cells. Notably, ECSOD has been shown to prevent oxidative fragmentation of the ECM components both in vitro and in vivo. In the ECM, ECSOD is known to bind to Heparan sulfate (HS) with high affinity . Therefore, fragmentation of HS by ROS may lead to dysregulation of ECSOD, inflammatory cells and cytokines and play a role in the mechanism of ROS-mediated lung fibrosis.

We hypothesize that ECSOD protects the lung from oxidant-induced damage and inflammation by preventing Heparin/Heparan sulfate (HS) fragmentation in the ECM. We utilize an in vivo system where Finally, we utilize in vitro fibroblast models, in vitro cell free H/HS models and in vivo mouse models to wild-type, ECSOD knockout and ECSOD transgenic mice will be used to analyze HS in the lung and its interactions with ECSOD.

Through this work, we propose that the interactions between ECSOD and HS provide a mechanism of lung protection and inflammatory regulation. Accomplishment of these aims will provide a better understanding of the mechanisms of oxidant injury and antioxidant activity in the lungs. Because the fibrotic pathology seen in IPF is very similar to that seen in asbestosis, the mechanisms resulting from this work will advance the knowledge of many other interstitial lung diseases. This can provide targets for the development of therapeutic agents for asbestosis and interstitial pulmonary injuries.

Publications:

Zheng M., Ramsay, A., Robichaux, M., Norris, K., Kliment, C., Crowe, C., Rapaka, R., Steele, C., McAllister, F., Shellito, J., Marrero, L., Schwarzenberger, P., Zhong, Q., Kolls, J., "CD4+ T cell-independent DNA vaccination against opportunistic infections," J. Clin. Invest., 2005 Dec 1;115(12):3536-3544.

Kliment, C, Tobolewski, J, Manni, M, Tan, R, Enghild, J, and Oury, T. Extracellular superoxide dismutase protects against matrix degradation of heparan sulfate in the lung. Antio. Redox Sign. 2008 Feb;10(2):261-8.

Myll?rniemi, M., Lindholm, P., Ryyn?nen, M., Kliment, C., Salmenkivi, K., Keski-Oja, J., Kinnula, V., Oury , T., and Koli, K. Gremlin-mediated decrease in BMP signaling promotes pulmonary fibrosis. Amer. J. Resp. Cri. Care Med. 2008 Feb 1;177(3):321-9.

Carraway, M.S., Suliman, H.B., Kliment, C.R., Oury, T.D., Welty-Wolf, K.E., and Piantadosi, C.A. Mitochondrial Biogenesis in the Pulmonary Vasculature during Inhalational Lung Injury and Fibrosis. Antio. Redox Sign. 2008 Feb; 10 (2):269-76.

Abstracts/Presentations

• Kliment, C, Tobolewski, J, Oury, T. Heparin/Heparan sulfate and EC-SOD Interactions in Pulmonary Fibrosis. Keystone International Symposium - Molecular Mechanisms of Fibrosis Meeting, Tahoe City, CA, March 11-14, 2007.
• Kliment, C.R., Romberger, D.J., Wyatt, T. Modulation of Airway Epithelial Cell Cytokine Release by Hog Barn Dust and Cigarette Smoke. American Thoracic Society (ATS) International Conference, Seattle, WA - May 2003, American Journal of Respiratory and Critical Care Medicine, Vol. 167, No. 7: p.A717.
• Kliment, C.R., Pardy, R.L. Analysis of the Biological Effects of Algal Lipopolysaccharide on Human Whole Blood. Nebraska Academy of Science Annual Meeting, April 25, 2003, Programs and Proceedings 2003: p.41.
• Kliment, C.R., Pardy, R.L. Analysis of the Biological Effects of Algal Lipopolysaccharide on Human Whole Blood. 17th Annual National Conference for Undergraduate Research, University of Utah, March 13-15, 2003, Abstract Book: p.249.
• Kliment, C.R., Romberger, D.J., Wyatt, T. Immunosuppressant Drugs Block IL-6 and IL-8 Release in Airway Epithelial Cells Exposed To Dust Extracts From Swine Confinement Facilities. American Thoracic Society (ATS) International Conference, Atlanta, GA - May 2002, American Journal of Respiratory and Critical Care Medicine, Vol. 165, No. 8: p.A525.

Awards:

• Medical Scientist Training Program (MSTP) Grant Recipient (Institutional, T32) - National Institutes of Health Sept. 2004-Sept. 2005, University of Pittsburgh School of Medicine