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Florida Faculty and Professional Staff
Thomas Schroeter
Associate Scientific Director I
Translational Research Institute
TSRI - 2001
Education
2001 Ph.D. Biochemistry J.W. Goethe University, Frankfurt (M), Germany
2001-2004 Postdoctoral Fellow, The Scripps Research Institute
Research Focus
As part of the Drug Discovery Team our group focuses on the characterization of small molecule kinase inhibitors of therapeutic interest. We are concentrating on the development of biochemical and cell-based functional assays using both high-content and high-throughput screening (HTS) technologies to optimize novel Rho kinase inhibitors for the treatment of Glaucoma. Aqueous humor is secreted by the ciliary epithelium into the anterior chamber which drains through the trabecular meshwork and into the Schlemm’s canal. During the development of glaucoma, cellular contraction and resistance in the trabecular meshwork results in reduced outflow and increased intraocular pressure leading to optic nerve degeneration and ultimately results in the loss of vision. Inhibition of ROCK activity increases outflow, lowers IOP, and preserves retinal neurons. In addition, the two isoforms of Rho kinase (ROCK1 an ROCK2) have non-redundant biological functions that are critical for the development of various diseases such as cancer, where we are actively investigating isoform contributions to disease development.
Our group also concentrates on the development of predictive toxicology screens. Emerging evidence points to the fact that activation of the ER-stress induced unfolded protein response (UPR) followed by apoptosis is partially responsible for drug induced organ toxicity. We are developing cell-based assays utilizing ER-stress pathways to address those questions.
Selected References
Chen YT, Bannister TD, Weiser A, Lin L, Cameron MD, Schurer SC, Duckett D, Schroter T, LoGrasso P, Feng Y. Chroman-3-amides as potent Rho kinase inhibitors. Bioorg Med Chem Lett (2008), 18:6406-6409
Feng Y, Yin Y, Weiser A, Griffin E, Cameron MD, Lin L, Ruiz C, Schurer SC, Inoue T, Rao VP, Schroter T, LoGrasso P. Discovery of substituted 4-(Pyrazol-4-yl-)-phenylbenzodioxane-2-carboxamides as potent and highly selective Rho kinase (ROCK-II) inhibitors. Journal of Medicinal Chemistry (2008), 51:6642-6645
Schroter T*, Griffin E, Weiser A, Feng Y, LoGrasso P. Detection of myosin light chain phosphorylation – a cell based assay for screening Rho-kinase inhibitors. Biochemical and Biophysical Research Communications (2008) 2:356-360 (*corresponding author)
Schroter T, Minond D, Weiser A, Dao C, Habel J, Spicer T, Chase P, Baillargeon P, Scampavia L, Schuerer S, Chung C, Mader C, Southern M, Tsinoremas N, LoGrasso P, Hodder P. Comparison of miniaturized time-resolved fluorescence energy transfer and enzyme-coupled
luciferase hig-throughput screening assay to discover inhibitors of Rho-kinase II (ROCK-II). Journal of Biomolecular Screening (2008) 13:17-28
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