Scott C. Schuyler
JobTitle： Associate Professor
CurrentJob： Associate Professor
E-mail： schuyler@mail.cgu.edu.tw
Phone： 3596
Education： Ph.D. in Cell and Developmental Biology, Harvard University, USA
Expertise： Cell Biology, Cell Cycle, Protein Biochemistry, Yeast Genetics
Website： https://scs03596.wixsite.com/scslab
Research Direction
Cancers have been the leading cause of death in Taiwan and Japan for the past 41 and 43 years, respectively, and currently are responsible for about 1/6th of deaths globally. Our goal is to enhance the effectiveness of paclitaxel, which is FDA approved for the treatment of more than 20 types of adult cancers. The therapeutic index of 10 nM paclitaxel, the clinically relevant amount to work with in lab cultured MDA-MB-231 cell lines, is hypothesized not to involve cell cycle arrest in mitosis, but rather may be derived from the formation of multipolar mitotic spindles that can lead to two different cell death fates after a mother cell with a multipolar spindle executes an aberrant mitosis. First, elevated levels of chromosome mis-segregation on the multipolar spindle may induce necrosis/apoptosis/quiescence in the daughter cells. Second, a lagging chromosome(s) in anaphase on the multipolar spindle of the mother cell may lead to a chromatin bridge(s) in cytokinesis that activate the cyclic GMP–AMP Synthase-Stimulator of Interferon Genes (cGAS-STING) pathway in the daughter cells which may promote type I interferon (IFN) secretion resulting in leukocyte recruitment into solid tumors which execute immunogenic cell death, a pathway that can also be activated during apoptosis and/or necrosis. The efficacy of paclitaxel has been enhanced by combinatorial therapies based on anti-immune checkpoint drugs targeting programmed death-ligand 1 (PD-L1)/programmed cell death protein 1 (PD-1). Many patients do not respond to paclitaxel treatments before critical limiting doses of paclitaxel are reached, caused by adverse side effects such as neutropenia, mucositis and/or neurotoxicity. Our approach is to specifically target the Anaphase-Promoting Complex/Cyclosome-Cell Division Cycle 20 (APC/C-CDC20) enzyme complex to try and delay anaphase entry without inducing a mitotic cell cycle arrest which may enhance the effectiveness of paclitaxel
Publications
2. Scott C. Schuyler. Editorial: Chromosome bi-orientation, tension and the spindle-assembly checkpoint. Front. Cell Dev. Biol. 2023 Jul. Volume 11
3. Scott C. Schuyler and Hsin-Yu Chen. Using budding yeast to identify molecules that block cancer cell 'mitotic slippage' only in the presence of mitotic poisons. Int. J. Mol. Sci. 2021 Jul. 22(15), 7985
4. Krishna B. S. Swamy, Scott C. Schuyler and Jun-Yi Leu. Protein Complexes Form a Basis for Complex Hybrid Incompatibility. Front. Genet. 2021 Feb 09; 12: 609766.
5. Scott C. Schuyler, Lin-Ing Wang, Yi-Shan Ding, Yi-Chieh Lee, and Hsin-Yu Chen. Deletion of Budding Yeast MAD2 Suppresses Clone-to-Clone Diferences in Artificial Linear Chromosome Copy Numbers and Gives Rise to Higher Retention Rates. Microorganisms. 2020 Sep 29;8(10):E1495