Karsten Gronert

Acting Associate Professor of Vision Science and Optometry; Solon M. and Pearl A. Braff Chair in Clinical Optometric Science; Center for Eye Disease & Development, UC Berkeley

Ocular inflammation/immunology and wound healing

A fundamental principle of an inflammatory event is the resolution and subsequent wound repair. These tightly orchestrated processes are essential to human health. However, our understanding of endogenous mechanisms that govern natural resolution of inflammation and promote wound repair is limited. Our research interests are focused on elucidating and defining the molecular mechanism of these protective pathways in the cornea, retina as well as the kidney. Of special interest are a novel class of lipid mediators, namely lipoxins and the recently identified docosahexaenoic acid-derived lipid signals coined resolvins and protectins. To establish a role for these lipid autacoids in regulating the inflammatory/reparative response, we employ a combined approach of LC/MS/MS-based lipidomic analyses, molecular biology and in vivo experiments in mice with targeted genetic deletions.

Lipoxins and the omega-3 fatty acid-derived Resolvins and Protectins exhibit potent protective properties and inhibit many of the cardinal signs of inflammation. Therefore, their biosynthetic pathways and molecular mechanisms of action are of primary interest as potential markers of inflammatory disease and as tools for therapeutic intervention. We recently discovered that these lipid anti-inflammatory and protective pathways are present in the cornea and retina. These exciting findings are part of a National Eye Institute funded research program that is focused on elucidating and delineating the formation and molecular mechanisms of these protective lipid signals in ocular inflammatory diseases and their role in limiting the sequelae of corneal injury.

Our long-term goals are to define protective circuits that regulate the execution of the essential inflammatory/reparative response and, thus, provide novel therapeutic approaches to minimize and control ocular damage and diseases.

Selected Publications

1. Serhan, C.N., Clish, C.B., Brannon, J., Colgan, S.P., Chiang, N. and Gronert, K. Novel functional sets of lipid-derived mediators with antiinflammatory actions generated from omega-3 fatty acids via cyclooxygenase 2-nonsteroidal antiinflammatory drugs and transcellular processing.  J. Exp. Med., 2000; 192: 1197-1204.
2. Gronert, K., Martinsson-Niskanen, T., Ravasi, S., Chiang, N., and Serhan, C.N. Selectivity of Recombinant Human Leukotriene D4, Leukotriene B4 and Lipoxin A4 Receptors with Aspirin-triggered 15-epi-LXA4 and Regulation of Vascular and Inflammatory Responses. Am. J. Path. 2001; 158:3.
3. Levy, B.D., Clish, C.B., Schmidt, B., Gronert, K., and Serhan C.N. Lipid mediator class switching during acute inflammation: signals in resolution. Nature Immunology., 2001; 2: 612-619.
4. Serhan, C.N., Hong, S., Gronert, K, Colgan, S.P., Devchand, P.R., Mirick, G., and Moussignac, R. Resolvins: a family of bioactive products of omega-3 fatty acid transformation circuits initiated by aspirin treatment that counter proinflammation signals. J Exp Med 2002; 196:1025-37.
5. Devchand, P.D, Song H., Makoto, A., Bannenberg, G., Gronert, K., and Serhan C.N. Human ALX receptor regulates inflammation and host-defense dynamics. FASEB 2003; 17:652-59.
6. Hong, S, Gronert, K., Devchand, P.R., Moussignac, RL, and Serhan, C.N. Novel docosatrienes and 17S-Resolvins generated from docosahexaenoic acid in murine brain, human blood and glial cells: Autacoids in anti-inflammation. J Biol Chem 2003; 278: 14677-87.
7. Marcheselli, V.L., Hong, S., Lukiw, W.J., Tian, X.H., Gronert, K., Musto, A., Hardy M., Gimenez, J.M., Chiang, N., Serhan, C.N., and Bazan, N.G. J. Biol. Chem. 2003; 278: 43807-43817.
8. Gronert, K., Kantarci, A., Levy, B.D., Clish, C.B., Odparlik, S., Hsturk, H., Badwey, J.A., Colgan, S.P., Van Dyke, T.E., and Serhan C.N. A molecular defect in intracellular lipid signaling in human neutrophils in localized aggressive periodontal tissue damage. J. Immunol. 2004; 172: 1856-1861.
9. Vance, R.E., Hong, S., Gronert, K., Serhan, C.N., and Mekalanos, J.J. The opportunistic pathogen Pseudomonas aeruginosa carries a secretable arachidonate 15-lipoxygenase. Proc. Nat. Acad. Sci. 2004; 101: 2135-2139.
10. Bannenberg, G., Moussignac, R.L., Gronert K., Devchand, P.R., Schmidt, B.A., Guilford, W., J., Bauman,  J.G., Subramanyam, B., Perez, H.D., Parkinson, J.F., and Serhan, C.N.  Lipoxins and novel 15-epi-lipoxin analogs display potent anti-inflammatory actions after oral administration. Br. J. Pharmacol. 2004; 143:43-52.
11. Gronert, K., Maheshwari, N., Khan, N., Hassan, I.R., Dunn, M. and Schwartzman-Laniado, M. A role for the 15-lipoxygenase pathway in promoting epithelial wound healing and host defense. J. Biol. Chem. 2005; 280: 15267-15278.
12. Gronert, K. Lipoxins in the eye and their role in wound healing.  Prostaglandins. Leukot. Essent. Fatty Acids. 2005: 73: 221-229.
13. Gonzalez-Periz, A., Planaguma, A., Gronert, K., Miquel, R., Lopez-Parra, M., Titos, E., Horrillo, R., Ferre, N., Deulofeu, R., Arroyo, V., Rodes, J., Claria, J. Docosahexaenoic acid (DHA) blunts liver injury by conversion to protective lipid mediators: Protectin D1 and 17S-hydroxy-DHA.  FASEB 2006; 20: 2537-2539.
14. Seta, F., Bellner, L., Rezzani, R., Regan, R.F., Dunn, M.W., Abraham, N.G., Gronert, K. and Laniado-Schwartzman, M.  Heme-oxygenase: A critical determinant for execution of an acute inflammatory and reparative response.  Am. J. Path., 2006; 169: 1612-1623.
15. Biteman, B., Hassan, I.R., Walker, E., Leedom, A.J., Dunn, M., Seta, F., Laniado-Schwartzman M. and Gronert, K. Interdependence of lipoxin A4 and heme-oxygenase in counter-regulating inflammation during corneal wound healing. FASEB 2007; 21(9): 2257-2266.
16. Gronert, K., Hassan I.R. Reaping the benefits of renal protective lipid autacoids. Drug Discovery Today: Disease Mechanisms, 2007 (in press).

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