Proteins that behave as switches hold great promise as selective protein therapeutics. Previous studies by the PI have demonstrated that protein switches can be engineered by creating a large number of different fusions between two genes and subjecting these gene fusions to evolution in the lab. Such directed evolution strategies will be used to develop and improve protein switches to effectively activate prodrugs selectively in cancer cells. These switches will be evaluated for their ability to eliminate tumor xenographs in vivo using endogenous expression and via systemic delivery. These switches in combination with the appropriate prodrug have potential as a targeted therapeutic for the treatment of cancer.
| Shelat, Nirav Y; Parhi, Sidhartha; Ostermeier, Marc (2017) Development of a cancer-marker activated enzymatic switch from the herpes simplex virus thymidine kinase. Protein Eng Des Sel 30:95-103 |
| Ribeiro, Lucas Ferreira; Tullman, Jennifer; Nicholes, Nathan et al. (2016) A xylose-stimulated xylanase-xylose binding protein chimera created by random nonhomologous recombination. Biotechnol Biofuels 9:119 |
| Shelat, Nirav Y; Parhi, Sidhartha; Ostermeier, Marc (2016) A Positive Selection for Nucleoside Kinases in E. coli. PLoS One 11:e0162921 |
| Choi, Jay H; Xiong, Tina; Ostermeier, Marc (2016) The interplay between effector binding and allostery in an engineered protein switch. Protein Sci 25:1605-16 |
| Choi, Jay H; Zayats, Maya; Searson, Peter C et al. (2016) Electrochemical activation of engineered protein switches. Biotechnol Bioeng 113:453-6 |
| Nicholes, N; Date, A; Beaujean, P et al. (2016) Modular protein switches derived from antibody mimetic proteins. Protein Eng Des Sel 29:77-85 |
| Choi, Jay H; Ostermeier, Marc (2015) Rational design of a fusion protein to exhibit disulfide-mediated logic gate behavior. ACS Synth Biol 4:400-6 |
| Choi, Jay H; Laurent, Abigail H; Hilser, Vincent J et al. (2015) Design of protein switches based on an ensemble model of allostery. Nat Commun 6:6968 |
| Chaikind, Brian; Ostermeier, Marc (2014) Directed evolution of improved zinc finger methyltransferases. PLoS One 9:e96931 |
| Wright, R Clay; Khakhar, Arjun; Eshleman, James R et al. (2014) Advancements in the development of HIF-1?-activated protein switches for use in enzyme prodrug therapy. PLoS One 9:e114032 |
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