My research in structural biology is aimed at understanding cell adhesion at the molecular level where protein-protein and protein-carbohydrate interactions ae critical. Biomolecular conformations and interactions are analyzed primarily by using high resolution NMR spectroscopy, circular dichrosim spectropolarimetry and computer modeling.
As models for these interactions, for example, we are strudying the solution conformations of platelet factor-4 cytokine family proteinsand haparin-derived short-chain glycosaminoglycans. We also are interested in studying protein/peptide dynamics and intra- and intermolecular forces which stabilize native structure.
In collaboration with Drs. Jim McCarthy and Leo Furcht, we are identifying cell adhesion - promoting peptides derived, for example, from fibronectin, laminin and type IV collagen. Computer models of these structures then allow us to design constrained peptides which have the same conformation and similar biologic activity.
Ultimately, my work will aid in the rational design of pharmaceutical drugs which help to control the spread of cancer, to combat stroke and heart disease, or to reduce viral infection.
Kumar, N., Ippel, H., Weber, C., Hackeng, T., Mayo, K.H. (2013) Protein lysine-Nζ alkylation and O-phosphorylation mediated by DTT-generated reactive oxygen species. Protein Sci. 22(3):327-46.
Dings, R.P., Haseman, J.R., Leslie, D.B., Luong, M., Dunn, D.L., Mayo, K.H. (2013) Bacterial membrane disrupting dodecapeptide SC4 improves survival of mice challenged with Pseudomonas aeruginosa. Biochim. Biophys. Acta. 1830(6): 3454-7.
Mulder, WJ, van der Schaft, DW, Hautvast, PA, Strijkers, GJ, Koning, GA, Storm, G. Mayo, KH, Griffioen, AW, and Nicolay, D. (2007) Early in vivo assessment of angiostatic therapy efficacy by molecular MRI. FASEB J. 21:378-83.
Chen, X. Dings, RP, Nesmelova, I, Debbert, S. Haseman, JR, Maxwell, J, Hoye, TR, Mayo, KH. (2006) Topomimetics of amphipathic beta-sheet and helix-forming bactericidal peptides neutralize lipopolysaccharide endotoxins. J. Med. Chem. 49:7754-7765.
Hellebrekers, DM, Castermans, K, Vire, E, Dings, RP, Hoebers, NT, Mayo, KH, Oude Egbrink, MG, Molema, G, Fuks, F, van England, M, Griffioen, AW (2006) Epigenetic regulation of tumor endothelial cell anergy: silencing of intercellular adhesion molecule-1 by histone modifications. Cancer Res. 66:10770-10777.
Thijssen, VLJL, Postel, R, Brandwijk, RJMGE, Dings, RPM, Nesmelova, I, Atijn, S, Verhofstad, Nakabbeppu, Y, Baum, LG, Bakkers, J, Mayo, KH, Poirier, F, Griffioen, AW (2006) Galectin-1 is essential in tumor angiogenesis and a target for anti-angiogenesis therapy. Proc. Natl. Acad. Sci. USA 103:15975-15980.
van Beijunm, RJ, Dings, RPM, van der Linden, E, Zwanns, BMM, Ramarkers, FCS, Mayo, KH, Griffioen, AW (2006) Gene expression of tumor angiogenesis dissected: specific targeting of colon cancer angiogenic vasculature. Blood 108: 2339-2348.